In this work, we reported doxorubicin-peptide conjugates (DPCs) with an extracellular tumor acid-responsive sphere-fiber transformation for enhanced residence in tumors. As illustrated in Scheme Scheme1,1, the chemotherapy drug doxorubicin (DOX) was coupled with a peptide (KIGLFRWR) to design a DPC molecule with assembly ability. First, the DPCs, driven by hydrophobic forces from the hydrophobic drug DOX and the IGL fragment, can form spherical DPC nanoparticles (DPC-NPs). Then, along with hydrogen bond between peptides, the aromatic amino acids F and W give the DPC-NPs the ability of self-assembly to DPC-nanofibers (DPC-NFs) due to π-π stacking. The step-by-step assembly process provides opportunities for morphological transformation control. To meet the particle size requirements for intravenous injection, the acid-responsive material 2,3-dimethylmaleic anhydride grafted polylysine, named the functional polylysine graft (FPG), was designed as a shielding layer for DPC-NPs and formed functional doxorubicin-peptide conjugate nanoparticles (FDPC-NPs) by an electrostatic interaction to avoid π-π stacking interactions and hydrogen bond between the DPC-NPs. Therefore, the FDPC-NPs could maintain an appropriate size in blood vessels until entering the tumor stroma by the EPR effect. When the FDPC-NPs passed through the blood vessel and entered the weakly acidic microenvironment of the tumor, the surface potential of the shield was reversed from negative to positive because of acid-sensitive 2,3-dimethylmaleic groups on the FPG. Therefore, FPG would separate from the DPC-NPs because of the mutual repulsion effect from the like charges. Then, DPC-NPs self-assembled into DPC-NFs, thereby staying in the tumor region for a long time. After that, the fibers degraded gradually and free drug penetrated into tumor cells, exerting sustained anti-tumor effect. This study is original and provides new ideas for the design of targeted and long-acting drug delivery systems for tumor therapy.

In this work, we reported doxorubicin-peptide conjugates (DPCs) with an extracellular tumor acid-responsive sphere-fiber transformation for enhanced residence in tumors. As illustrated in Scheme Scheme1,1, the chemotherapy drug doxorubicin (DOX) was coupled with a peptide (KIGLFRWR) to design a DPC molecule with assembly ability. First, the DPCs, driven by hydrophobic forces from the hydrophobic drug DOX and the IGL fragment, can form spherical DPC nanoparticles (DPC-NPs). Then, along with hydrogen bond between peptides, the aromatic amino acids F and W give the DPC-NPs the ability of self-assembly to DPC-nanofibers (DPC-NFs) due to π-π stacking. The step-by-step assembly process provides opportunities for morphological transformation control. To meet the particle size requirements for intravenous injection, the acid-responsive material 2,3-dimethylmaleic anhydride grafted polylysine, named the functional polylysine graft (FPG), was designed as a shielding layer for DPC-NPs and formed functional doxorubicin-peptide conjugate nanoparticles (FDPC-NPs) by an electrostatic interaction to avoid π-π stacking interactions and hydrogen bond between the DPC-NPs. Therefore, the FDPC-NPs could maintain an appropriate size in blood vessels until entering the tumor stroma by the EPR effect. When the FDPC-NPs passed through the blood vessel and entered the weakly acidic microenvironment of the tumor, the surface potential of the shield was reversed from negative to positive because of acid-sensitive 2,3-dimethylmaleic groups on the FPG. Therefore, FPG would separate from the DPC-NPs because of the mutual repulsion effect from the like charges. Then, DPC-NPs self-assembled into DPC-NFs, thereby staying in the tumor region for a long time. After that, the fibers degraded gradually and free drug penetrated into tumor cells, exerting sustained anti-tumor effect. This study is original and provides new ideas for the design of targeted and long-acting drug delivery systems for tumor therapy.

In this work, we reported doxorubicin-peptide conjugates (DPCs) with an extracellular tumor acid-responsive sphere-fiber transformation for enhanced residence in tumors. As illustrated in Scheme Scheme1,1, the chemotherapy drug doxorubicin (DOX) was coupled with a peptide (KIGLFRWR) to design a DPC molecule with assembly ability. First, the DPCs, driven by hydrophobic forces from the hydrophobic drug DOX and the IGL fragment, can form spherical DPC nanoparticles (DPC-NPs). Then, along with hydrogen bond between peptides, the aromatic amino acids F and W give the DPC-NPs the ability of self-assembly to DPC-nanofibers (DPC-NFs) due to π-π stacking. The step-by-step assembly process provides opportunities for morphological transformation control. To meet the particle size requirements for intravenous injection, the acid-responsive material 2,3-dimethylmaleic anhydride grafted polylysine, named the functional polylysine graft (FPG), was designed as a shielding layer for DPC-NPs and formed functional doxorubicin-peptide conjugate nanoparticles (FDPC-NPs) by an electrostatic interaction to avoid π-π stacking interactions and hydrogen bond between the DPC-NPs. Therefore, the FDPC-NPs could maintain an appropriate size in blood vessels until entering the tumor stroma by the EPR effect. When the FDPC-NPs passed through the blood vessel and entered the weakly acidic microenvironment of the tumor, the surface potential of the shield was reversed from negative to positive because of acid-sensitive 2,3-dimethylmaleic groups on the FPG. Therefore, FPG would separate from the DPC-NPs because of the mutual repulsion effect from the like charges. Then, DPC-NPs self-assembled into DPC-NFs, thereby staying in the tumor region for a long time. After that, the fibers degraded gradually and free drug penetrated into tumor cells, exerting sustained anti-tumor effect. This study is original and provides new ideas for the design of targeted and long-acting drug delivery systems for tumor therapy.

In this work, we reported doxorubicin-peptide conjugates (DPCs) with an extracellular tumor acid-responsive sphere-fiber transformation for enhanced residence in tumors. As illustrated in Scheme Scheme1,1, the chemotherapy drug doxorubicin (DOX) was coupled with a peptide (KIGLFRWR) to design a DPC molecule with assembly ability. First, the DPCs, driven by hydrophobic forces from the hydrophobic drug DOX and the IGL fragment, can form spherical DPC nanoparticles (DPC-NPs). Then, along with hydrogen bond between peptides, the aromatic amino acids F and W give the DPC-NPs the ability of self-assembly to DPC-nanofibers (DPC-NFs) due to π-π stacking. The step-by-step assembly process provides opportunities for morphological transformation control. To meet the particle size requirements for intravenous injection, the acid-responsive material 2,3-dimethylmaleic anhydride grafted polylysine, named the functional polylysine graft (FPG), was designed as a shielding layer for DPC-NPs and formed functional doxorubicin-peptide conjugate nanoparticles (FDPC-NPs) by an electrostatic interaction to avoid π-π stacking interactions and hydrogen bond between the DPC-NPs. Therefore, the FDPC-NPs could maintain an appropriate size in blood vessels until entering the tumor stroma by the EPR effect. When the FDPC-NPs passed through the blood vessel and entered the weakly acidic microenvironment of the tumor, the surface potential of the shield was reversed from negative to positive because of acid-sensitive 2,3-dimethylmaleic groups on the FPG. Therefore, FPG would separate from the DPC-NPs because of the mutual repulsion effect from the like charges. Then, DPC-NPs self-assembled into DPC-NFs, thereby staying in the tumor region for a long time. After that, the fibers degraded gradually and free drug penetrated into tumor cells, exerting sustained anti-tumor effect. This study is original and provides new ideas for the design of targeted and long-acting drug delivery systems for tumor therapy.

In this work, we reported doxorubicin-peptide conjugates (DPCs) with an extracellular tumor acid-responsive sphere-fiber transformation for enhanced residence in tumors. As illustrated in Scheme Scheme1,1, the chemotherapy drug doxorubicin (DOX) was coupled with a peptide (KIGLFRWR) to design a DPC molecule with assembly ability. First, the DPCs, driven by hydrophobic forces from the hydrophobic drug DOX and the IGL fragment, can form spherical DPC nanoparticles (DPC-NPs). Then, along with hydrogen bond between peptides, the aromatic amino acids F and W give the DPC-NPs the ability of self-assembly to DPC-nanofibers (DPC-NFs) due to π-π stacking. The step-by-step assembly process provides opportunities for morphological transformation control. To meet the particle size requirements for intravenous injection, the acid-responsive material 2,3-dimethylmaleic anhydride grafted polylysine, named the functional polylysine graft (FPG), was designed as a shielding layer for DPC-NPs and formed functional doxorubicin-peptide conjugate nanoparticles (FDPC-NPs) by an electrostatic interaction to avoid π-π stacking interactions and hydrogen bond between the DPC-NPs. Therefore, the FDPC-NPs could maintain an appropriate size in blood vessels until entering the tumor stroma by the EPR effect. When the FDPC-NPs passed through the blood vessel and entered the weakly acidic microenvironment of the tumor, the surface potential of the shield was reversed from negative to positive because of acid-sensitive 2,3-dimethylmaleic groups on the FPG. Therefore, FPG would separate from the DPC-NPs because of the mutual repulsion effect from the like charges. Then, DPC-NPs self-assembled into DPC-NFs, thereby staying in the tumor region for a long time. After that, the fibers degraded gradually and free drug penetrated into tumor cells, exerting sustained anti-tumor effect. This study is original and provides new ideas for the design of targeted and long-acting drug delivery systems for tumor therapy.

In this work, we reported doxorubicin-peptide conjugates (DPCs) with an extracellular tumor acid-responsive sphere-fiber transformation for enhanced residence in tumors. As illustrated in Scheme Scheme1,1, the chemotherapy drug doxorubicin (DOX) was coupled with a peptide (KIGLFRWR) to design a DPC molecule with assembly ability. First, the DPCs, driven by hydrophobic forces from the hydrophobic drug DOX and the IGL fragment, can form spherical DPC nanoparticles (DPC-NPs). Then, along with hydrogen bond between peptides, the aromatic amino acids F and W give the DPC-NPs the ability of self-assembly to DPC-nanofibers (DPC-NFs) due to π-π stacking. The step-by-step assembly process provides opportunities for morphological transformation control. To meet the particle size requirements for intravenous injection, the acid-responsive material 2,3-dimethylmaleic anhydride grafted polylysine, named the functional polylysine graft (FPG), was designed as a shielding layer for DPC-NPs and formed functional doxorubicin-peptide conjugate nanoparticles (FDPC-NPs) by an electrostatic interaction to avoid π-π stacking interactions and hydrogen bond between the DPC-NPs. Therefore, the FDPC-NPs could maintain an appropriate size in blood vessels until entering the tumor stroma by the EPR effect. When the FDPC-NPs passed through the blood vessel and entered the weakly acidic microenvironment of the tumor, the surface potential of the shield was reversed from negative to positive because of acid-sensitive 2,3-dimethylmaleic groups on the FPG. Therefore, FPG would separate from the DPC-NPs because of the mutual repulsion effect from the like charges. Then, DPC-NPs self-assembled into DPC-NFs, thereby staying in the tumor region for a long time. After that, the fibers degraded gradually and free drug penetrated into tumor cells, exerting sustained anti-tumor effect. This study is original and provides new ideas for the design of targeted and long-acting drug delivery systems for tumor therapy.

In this work, we reported doxorubicin-peptide conjugates (DPCs) with an extracellular tumor acid-responsive sphere-fiber transformation for enhanced residence in tumors. As illustrated in Scheme Scheme1,1, the chemotherapy drug doxorubicin (DOX) was coupled with a peptide (KIGLFRWR) to design a DPC molecule with assembly ability. First, the DPCs, driven by hydrophobic forces from the hydrophobic drug DOX and the IGL fragment, can form spherical DPC nanoparticles (DPC-NPs). Then, along with hydrogen bond between peptides, the aromatic amino acids F and W give the DPC-NPs the ability of self-assembly to DPC-nanofibers (DPC-NFs) due to π-π stacking. The step-by-step assembly process provides opportunities for morphological transformation control. To meet the particle size requirements for intravenous injection, the acid-responsive material 2,3-dimethylmaleic anhydride grafted polylysine, named the functional polylysine graft (FPG), was designed as a shielding layer for DPC-NPs and formed functional doxorubicin-peptide conjugate nanoparticles (FDPC-NPs) by an electrostatic interaction to avoid π-π stacking interactions and hydrogen bond between the DPC-NPs. Therefore, the FDPC-NPs could maintain an appropriate size in blood vessels until entering the tumor stroma by the EPR effect. When the FDPC-NPs passed through the blood vessel and entered the weakly acidic microenvironment of the tumor, the surface potential of the shield was reversed from negative to positive because of acid-sensitive 2,3-dimethylmaleic groups on the FPG. Therefore, FPG would separate from the DPC-NPs because of the mutual repulsion effect from the like charges. Then, DPC-NPs self-assembled into DPC-NFs, thereby staying in the tumor region for a long time. After that, the fibers degraded gradually and free drug penetrated into tumor cells, exerting sustained anti-tumor effect. This study is original and provides new ideas for the design of targeted and long-acting drug delivery systems for tumor therapy.

In this work, we reported doxorubicin-peptide conjugates (DPCs) with an extracellular tumor acid-responsive sphere-fiber transformation for enhanced residence in tumors. As illustrated in Scheme Scheme1,1, the chemotherapy drug doxorubicin (DOX) was coupled with a peptide (KIGLFRWR) to design a DPC molecule with assembly ability. First, the DPCs, driven by hydrophobic forces from the hydrophobic drug DOX and the IGL fragment, can form spherical DPC nanoparticles (DPC-NPs). Then, along with hydrogen bond between peptides, the aromatic amino acids F and W give the DPC-NPs the ability of self-assembly to DPC-nanofibers (DPC-NFs) due to π-π stacking. The step-by-step assembly process provides opportunities for morphological transformation control. To meet the particle size requirements for intravenous injection, the acid-responsive material 2,3-dimethylmaleic anhydride grafted polylysine, named the functional polylysine graft (FPG), was designed as a shielding layer for DPC-NPs and formed functional doxorubicin-peptide conjugate nanoparticles (FDPC-NPs) by an electrostatic interaction to avoid π-π stacking interactions and hydrogen bond between the DPC-NPs. Therefore, the FDPC-NPs could maintain an appropriate size in blood vessels until entering the tumor stroma by the EPR effect. When the FDPC-NPs passed through the blood vessel and entered the weakly acidic microenvironment of the tumor, the surface potential of the shield was reversed from negative to positive because of acid-sensitive 2,3-dimethylmaleic groups on the FPG. Therefore, FPG would separate from the DPC-NPs because of the mutual repulsion effect from the like charges. Then, DPC-NPs self-assembled into DPC-NFs, thereby staying in the tumor region for a long time. After that, the fibers degraded gradually and free drug penetrated into tumor cells, exerting sustained anti-tumor effect. This study is original and provides new ideas for the design of targeted and long-acting drug delivery systems for tumor therapy.

In this work, we reported doxorubicin-peptide conjugates (DPCs) with an extracellular tumor acid-responsive sphere-fiber transformation for enhanced residence in tumors. As illustrated in Scheme Scheme1,1, the chemotherapy drug doxorubicin (DOX) was coupled with a peptide (KIGLFRWR) to design a DPC molecule with assembly ability. First, the DPCs, driven by hydrophobic forces from the hydrophobic drug DOX and the IGL fragment, can form spherical DPC nanoparticles (DPC-NPs). Then, along with hydrogen bond between peptides, the aromatic amino acids F and W give the DPC-NPs the ability of self-assembly to DPC-nanofibers (DPC-NFs) due to π-π stacking. The step-by-step assembly process provides opportunities for morphological transformation control. To meet the particle size requirements for intravenous injection, the acid-responsive material 2,3-dimethylmaleic anhydride grafted polylysine, named the functional polylysine graft (FPG), was designed as a shielding layer for DPC-NPs and formed functional doxorubicin-peptide conjugate nanoparticles (FDPC-NPs) by an electrostatic interaction to avoid π-π stacking interactions and hydrogen bond between the DPC-NPs. Therefore, the FDPC-NPs could maintain an appropriate size in blood vessels until entering the tumor stroma by the EPR effect. When the FDPC-NPs passed through the blood vessel and entered the weakly acidic microenvironment of the tumor, the surface potential of the shield was reversed from negative to positive because of acid-sensitive 2,3-dimethylmaleic groups on the FPG. Therefore, FPG would separate from the DPC-NPs because of the mutual repulsion effect from the like charges. Then, DPC-NPs self-assembled into DPC-NFs, thereby staying in the tumor region for a long time. After that, the fibers degraded gradually and free drug penetrated into tumor cells, exerting sustained anti-tumor effect. This study is original and provides new ideas for the design of targeted and long-acting drug delivery systems for tumor therapy.

In this work, we reported doxorubicin-peptide conjugates (DPCs) with an extracellular tumor acid-responsive sphere-fiber transformation for enhanced residence in tumors. As illustrated in Scheme Scheme1,1, the chemotherapy drug doxorubicin (DOX) was coupled with a peptide (KIGLFRWR) to design a DPC molecule with assembly ability. First, the DPCs, driven by hydrophobic forces from the hydrophobic drug DOX and the IGL fragment, can form spherical DPC nanoparticles (DPC-NPs). Then, along with hydrogen bond between peptides, the aromatic amino acids F and W give the DPC-NPs the ability of self-assembly to DPC-nanofibers (DPC-NFs) due to π-π stacking. The step-by-step assembly process provides opportunities for morphological transformation control. To meet the particle size requirements for intravenous injection, the acid-responsive material 2,3-dimethylmaleic anhydride grafted polylysine, named the functional polylysine graft (FPG), was designed as a shielding layer for DPC-NPs and formed functional doxorubicin-peptide conjugate nanoparticles (FDPC-NPs) by an electrostatic interaction to avoid π-π stacking interactions and hydrogen bond between the DPC-NPs. Therefore, the FDPC-NPs could maintain an appropriate size in blood vessels until entering the tumor stroma by the EPR effect. When the FDPC-NPs passed through the blood vessel and entered the weakly acidic microenvironment of the tumor, the surface potential of the shield was reversed from negative to positive because of acid-sensitive 2,3-dimethylmaleic groups on the FPG. Therefore, FPG would separate from the DPC-NPs because of the mutual repulsion effect from the like charges. Then, DPC-NPs self-assembled into DPC-NFs, thereby staying in the tumor region for a long time. After that, the fibers degraded gradually and free drug penetrated into tumor cells, exerting sustained anti-tumor effect. This study is original and provides new ideas for the design of targeted and long-acting drug delivery systems for tumor therapy.

In this work, we reported doxorubicin-peptide conjugates (DPCs) with an extracellular tumor acid-responsive sphere-fiber transformation for enhanced residence in tumors. As illustrated in Scheme Scheme1,1, the chemotherapy drug doxorubicin (DOX) was coupled with a peptide (KIGLFRWR) to design a DPC molecule with assembly ability. First, the DPCs, driven by hydrophobic forces from the hydrophobic drug DOX and the IGL fragment, can form spherical DPC nanoparticles (DPC-NPs). Then, along with hydrogen bond between peptides, the aromatic amino acids F and W give the DPC-NPs the ability of self-assembly to DPC-nanofibers (DPC-NFs) due to π-π stacking. The step-by-step assembly process provides opportunities for morphological transformation control. To meet the particle size requirements for intravenous injection, the acid-responsive material 2,3-dimethylmaleic anhydride grafted polylysine, named the functional polylysine graft (FPG), was designed as a shielding layer for DPC-NPs and formed functional doxorubicin-peptide conjugate nanoparticles (FDPC-NPs) by an electrostatic interaction to avoid π-π stacking interactions and hydrogen bond between the DPC-NPs. Therefore, the FDPC-NPs could maintain an appropriate size in blood vessels until entering the tumor stroma by the EPR effect. When the FDPC-NPs passed through the blood vessel and entered the weakly acidic microenvironment of the tumor, the surface potential of the shield was reversed from negative to positive because of acid-sensitive 2,3-dimethylmaleic groups on the FPG. Therefore, FPG would separate from the DPC-NPs because of the mutual repulsion effect from the like charges. Then, DPC-NPs self-assembled into DPC-NFs, thereby staying in the tumor region for a long time. After that, the fibers degraded gradually and free drug penetrated into tumor cells, exerting sustained anti-tumor effect. This study is original and provides new ideas for the design of targeted and long-acting drug delivery systems for tumor therapy.

In this work, we reported doxorubicin-peptide conjugates (DPCs) with an extracellular tumor acid-responsive sphere-fiber transformation for enhanced residence in tumors. As illustrated in Scheme Scheme1,1, the chemotherapy drug doxorubicin (DOX) was coupled with a peptide (KIGLFRWR) to design a DPC molecule with assembly ability. First, the DPCs, driven by hydrophobic forces from the hydrophobic drug DOX and the IGL fragment, can form spherical DPC nanoparticles (DPC-NPs). Then, along with hydrogen bond between peptides, the aromatic amino acids F and W give the DPC-NPs the ability of self-assembly to DPC-nanofibers (DPC-NFs) due to π-π stacking. The step-by-step assembly process provides opportunities for morphological transformation control. To meet the particle size requirements for intravenous injection, the acid-responsive material 2,3-dimethylmaleic anhydride grafted polylysine, named the functional polylysine graft (FPG), was designed as a shielding layer for DPC-NPs and formed functional doxorubicin-peptide conjugate nanoparticles (FDPC-NPs) by an electrostatic interaction to avoid π-π stacking interactions and hydrogen bond between the DPC-NPs. Therefore, the FDPC-NPs could maintain an appropriate size in blood vessels until entering the tumor stroma by the EPR effect. When the FDPC-NPs passed through the blood vessel and entered the weakly acidic microenvironment of the tumor, the surface potential of the shield was reversed from negative to positive because of acid-sensitive 2,3-dimethylmaleic groups on the FPG. Therefore, FPG would separate from the DPC-NPs because of the mutual repulsion effect from the like charges. Then, DPC-NPs self-assembled into DPC-NFs, thereby staying in the tumor region for a long time. After that, the fibers degraded gradually and free drug penetrated into tumor cells, exerting sustained anti-tumor effect. This study is original and provides new ideas for the design of targeted and long-acting drug delivery systems for tumor therapy.

In this work, we reported doxorubicin-peptide conjugates (DPCs) with an extracellular tumor acid-responsive sphere-fiber transformation for enhanced residence in tumors. As illustrated in Scheme Scheme1,1, the chemotherapy drug doxorubicin (DOX) was coupled with a peptide (KIGLFRWR) to design a DPC molecule with assembly ability. First, the DPCs, driven by hydrophobic forces from the hydrophobic drug DOX and the IGL fragment, can form spherical DPC nanoparticles (DPC-NPs). Then, along with hydrogen bond between peptides, the aromatic amino acids F and W give the DPC-NPs the ability of self-assembly to DPC-nanofibers (DPC-NFs) due to π-π stacking. The step-by-step assembly process provides opportunities for morphological transformation control. To meet the particle size requirements for intravenous injection, the acid-responsive material 2,3-dimethylmaleic anhydride grafted polylysine, named the functional polylysine graft (FPG), was designed as a shielding layer for DPC-NPs and formed functional doxorubicin-peptide conjugate nanoparticles (FDPC-NPs) by an electrostatic interaction to avoid π-π stacking interactions and hydrogen bond between the DPC-NPs. Therefore, the FDPC-NPs could maintain an appropriate size in blood vessels until entering the tumor stroma by the EPR effect. When the FDPC-NPs passed through the blood vessel and entered the weakly acidic microenvironment of the tumor, the surface potential of the shield was reversed from negative to positive because of acid-sensitive 2,3-dimethylmaleic groups on the FPG. Therefore, FPG would separate from the DPC-NPs because of the mutual repulsion effect from the like charges. Then, DPC-NPs self-assembled into DPC-NFs, thereby staying in the tumor region for a long time. After that, the fibers degraded gradually and free drug penetrated into tumor cells, exerting sustained anti-tumor effect. This study is original and provides new ideas for the design of targeted and long-acting drug delivery systems for tumor therapy.

In this work, we reported doxorubicin-peptide conjugates (DPCs) with an extracellular tumor acid-responsive sphere-fiber transformation for enhanced residence in tumors. As illustrated in Scheme Scheme1,1, the chemotherapy drug doxorubicin (DOX) was coupled with a peptide (KIGLFRWR) to design a DPC molecule with assembly ability. First, the DPCs, driven by hydrophobic forces from the hydrophobic drug DOX and the IGL fragment, can form spherical DPC nanoparticles (DPC-NPs). Then, along with hydrogen bond between peptides, the aromatic amino acids F and W give the DPC-NPs the ability of self-assembly to DPC-nanofibers (DPC-NFs) due to π-π stacking. The step-by-step assembly process provides opportunities for morphological transformation control. To meet the particle size requirements for intravenous injection, the acid-responsive material 2,3-dimethylmaleic anhydride grafted polylysine, named the functional polylysine graft (FPG), was designed as a shielding layer for DPC-NPs and formed functional doxorubicin-peptide conjugate nanoparticles (FDPC-NPs) by an electrostatic interaction to avoid π-π stacking interactions and hydrogen bond between the DPC-NPs. Therefore, the FDPC-NPs could maintain an appropriate size in blood vessels until entering the tumor stroma by the EPR effect. When the FDPC-NPs passed through the blood vessel and entered the weakly acidic microenvironment of the tumor, the surface potential of the shield was reversed from negative to positive because of acid-sensitive 2,3-dimethylmaleic groups on the FPG. Therefore, FPG would separate from the DPC-NPs because of the mutual repulsion effect from the like charges. Then, DPC-NPs self-assembled into DPC-NFs, thereby staying in the tumor region for a long time. After that, the fibers degraded gradually and free drug penetrated into tumor cells, exerting sustained anti-tumor effect. This study is original and provides new ideas for the design of targeted and long-acting drug delivery systems for tumor therapy.