pH-responsive morphology shifting peptides coloaded with paclitaxel and sorafenib inhibit angiogenesis and tumor growth

Chemotherapeutic drugs have low aggregation rates and short retention times in tumors, severely limiting their clinical application. Additionally, the development and spread of solid tumors is highly dependent on neovascularization. An RGD-modified acid-responsive peptide was designed to encapsulate the chemotherapeutic drug paclitaxel (PTX) and the antiangiogenic drug sorafenib (SF), enabling them to self-assemble into nanoparticles (NPs) in a physiological environment. In an acidic environment, the release of PTX and SF was achieved when the drug-loaded experimental peptide PS/Pep1 transformed from spherical NPs into aggregates containing nanofibers, which effectively prolonged the retention of the encapsulated drug and increased drug accumulation. Furthermore, in vivo experiments provided compelling evidence of the strong inhibitory effects of PS/Pep1 on tumor growth and metastasis, as well as its effective suppression of angiogenesis. This targeted NP system that undergoes a morphological shift in the tumor microenvironment holds promise for enhancing the efficacy of the combined administration of chemotherapeutic and antiangiogenic drugs to inhibit tumor growth and metastasis.