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.

Docetaxel (TXT) is acknowledged as one of the most important chemotherapy agents for gastric cancer (GC). PI3K/AKT signaling is frequently activated in GC, and its inhibitor LY294002 exerts potent antitumor effects. However, the hydrophobicity of TXT and the poor solubility and low bioavailability of LY294002 limit their clinical application. To overcome these shortcomings, we developed poly(lactic acid/glycolic) (PLGA) nanoparticles loaded with TXT and LY294002. PLGA facilitated the accumulation of TXT and LY294002 at the tumor sites. The in vitro functional results showed that PLGA(TXT+LY294002) exhibited controlled-release and resulted in a markedly reduced proliferative capacity and an elevated apoptosis rate. An in vivo orthotopic GC mouse model and xenograft mouse model confirmed the anticancer superiority and tumor-targeting feature of PLGA(TXT+LY294002). Histological analysis indicated that PLGA(TXT+LY294002) was biocompatible and had no toxicity to major organs. Characterized by the combined slow release of TXT and LY294002, this novel PLGA-based TXT/LY294002 drug delivery system provides controlled release and tumor targeting and is safe, shedding light on the future of targeted therapy against GC.

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