Therapy for Gastric Cancer with Peritoneal Metastasis Using Injectable Albumin Hydrogel Hybridized with Paclitaxel-Loaded Red Blood Cell Membrane Nanoparticles

The local delivery of therapeutics in a long-term sustained manner at tumor sites is attractive for the therapy of gastric cancer with peritoneal metastasis. In this manuscript, an injectable hydrogel-encapsulating paclitaxel-loaded red blood cell membrane nanoparticles (PRNP-gel) is designed on the basis of temperature-induced phase transition of polyethylene-glycol-modified bovine serum albumin (PEG-BSA). Dynamic light scattering, ζ potential, and electron microscopy were utilized to characterize the nanoparticle–hydrogel hybrid system. It was found that the PRNP had a spherical morphology with a diameter of about 133 nm and negative surface potential. The drug loading efficiency and loading content are 85% and 22%, respectively. In situ gelation occurred within 12 min when the gel precursor was incubated at 37 °C or injected subcutaneously. The in-situ-forming hydrogel showed a sustained release profile, and the cumulative release of PTX was ～30% after 6 days. The PRNP-gel exhibited high cytocompatibility and biodegradability in vitro and in vivo. This nanoparticle–hydrogel hybrid system is applied as a drug carrier for local chemotherapy to enhance therapeutic levels at tumor site and reduce the systemic toxicity. In vivo antitumor evaluation within a subcutaneous xenograft and peritoneal dissemination model showed that the hydrogel possesses good tumor growth suppression properties after a single injection. Hence, the as-prepared injectable hydrogel system could be a promising candidate for the local delivery of chemotherapeutic drugs