Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.

Next, we compared the breast cancer cell uptake of the two cyclic peptides,7and8(with alll-amino acids), versus the noncancerous cell uptake to three previously reported lead sequences (linear peptides), namely,1,2, and4. Two peptide concentrations were used, 1 μM and 10 μM. As shown inFigure S3, the magnitude of cell uptake increased considerably at higher peptide concentration (10 μM). The intensity of cell-associated fluorescence at 10 μM peptide concentration was at least 2-fold higher when compared to the cell-associated fluorescence observed at 1 μM peptide concentration. This trend was observed for all breast cancer cell lines used in the study. The mean fluorescence intensities (MFIs) of FITC-7at 10 μM were 2771 ± 78, 2607 ± 116, and 1761 ± 83 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively, whereas the MFIs were 179 ± 25 and 247 ± 27, respectively, when incubated with normal HUVEC and MCF10A. In comparison, the MFIs for the linear peptide with twod-amino acids x and k (FITC-4) were 965 ± 44, 1666 ± 97, and 1031 ± 54 when incubated with MCF-7, MDA-MB-231, and MDA-MB-435, respectively. Overall the uptake was observed in the following order1<2<4<7<8with peptide8displaying highest cellular uptake. Noncancerous cell uptake (HUVEC and breast tissue derived MCF-10A cells) of all the peptides was minimal. Even at high peptide concentration (10 μM) the uptake of the peptides was low suggesting the presence of smaller number of putative receptors on these cells.