Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

Subsequently, the antiproliferative activities of the PS conjugates, including dark toxicity and phototoxicity (660 nM, light dose: 10 J/cm²), were evaluated. Dark toxicity refers to the toxicity of PS conjugates against cancer cells in the absence of light and can be regarded as a crucial measure of the safety profile, while phototoxicity is the most direct indicator of the PDT efficacy of PS. The results showed that the dark toxicity of all the compounds against the five cell lines was comparatively low, demonstrating that the PS conjugates exhibited a high safety index in the absence of light. Compound 8b exhibited the optimum tumor cell selectivity in terms of phototoxicity, with the IC50 values of 0.82 uM against HepG2 cells and 2.4 uM against Huh-7 cells, respectively, whereas its toxicity against GPC3-negative cell lines was >10 uM. Although compounds 8a and 8c-d exhibited excellent phototoxicity against HepG2 and Huh-7 cells, (IC50 range: 0.2-2.0 uM), these compounds lacked selectivity between GPC3-overexpressed and GPC3-negative cells because they also showed considerable phototoxicity against the cell lines with minimal GPC3 expression. Notably, compound 1 showed low phototoxicity and selectivity against all the tested cell lines (IC50 > 10 uM).

The internalization of nanoparticles in cancer cells is the foremost step in PDT. Targeting ligand decoration and reducing nanoparticle size have been intensively explored to enhance the intracellular uptake of nanoparticles. Therefore, the PPC nanoparticles were designed to offer the appropriate size and targeting ability for delivery of Ce6 to tumor tissues via active and passive targeting mechanisms. The cellular internalization of free Ce6 and PPC into various cancer cells, i.e., MDA-MB-231, MKN-28, and HeLa, was assessed by fluorescence-activated cell sorting (FACS) analysis using a flow cytometer. When compared with free Ce6, the higher cellular internalization of PPC was observed in all cancer cells tested. In particular, the fluorescence intensity due to the intracellular uptake of PPC in MDA-MB-231 cells increased more dramatically than in the other cancer cells.