Neuropilin-1-Targeted Nanomedicine for Spatiotemporal Tumor Suppression through Photodynamic Vascular Damage and Antiangiogenesis

• Published in: ACS applied materials & interfaces 2024-05, Vol.16 (17), p.21709-21721
• Main Authors: Li, Xin-Yu, Yan, Ni, Wu, Ye-Yang, Kong, Ren-Jiang, Qiu, Zi-Wen, Liu, Shu-Peng, Wu, De-Hua, Cheng, Hong
• Format: Article
• Language: English
• Subjects: angiogenesis; Angiogenesis Inhibitors - chemistry; Angiogenesis Inhibitors - pharmacology; Animals; apoptosis; Apoptosis - drug effects; Axitinib - chemistry; Axitinib - pharmacology; Axitinib - therapeutic use; Biological and Medical Applications of Materials and Interfaces; breast neoplasms; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Tumor; drugs; Female; Human Umbilical Vein Endothelial Cells; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Nanomedicine; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - pathology; Neuropilin-1 - metabolism; peptides; Photochemotherapy; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Photosensitizing Agents - therapeutic use; reactive oxygen species; Reactive Oxygen Species - metabolism; relapse; vascular endothelial growth factor receptors
• ISSN: 1944-8244; 1944-8252; 1944-8252
• DOI: 10.1021/acsami.4c03886

Antiangiogenic therapy is an effective way to disrupt nutrient supply and starve tumors, but it is restricted by poor efficacy and negative feedback-induced tumor relapse. In this study, a neuropilin-1 (NRP-1)-targeted nanomedicine (designated as FPPT@Axi) is reported for spatiotemporal tumor suppression by combining photodynamic therapy (PDT) with antiangiogenesis. In brief, FPPT@Axi is prepared by utilizing an NRP-1-targeting chimeric peptide (Fmoc-K­(PpIX)-PEG8-TKPRR) to encapsulate the antiangiogenic drug Axitinib (Axi). Importantly, the NRP-1-mediated targeting property enables FPPT@Axi to selectively concentrate at vascular endothelial and breast cancer cells, facilitating the production of reactive oxygen species (ROS) in situ for specific vascular disruption and enhanced cell apoptosis under light stimulation. Moreover, the codelivered Axi can further inhibit vascular endothelial growth factor receptor (VEGFR) to impair the negative feedback of PDT-induced tumor neovascularization. Consequently, FPPT@Axi spatiotemporally restrains the tumor growth through blocking angiogenesis, destroying tumor vessels, and inducing tumor apoptosis. Such an NRP-1-mediated targeting codelivery system sheds light on constructing an appealing candidate with translational potential by using clinically approved PDT and chemotherapy.