Potential of Platelet-Based Drug Delivery System for Treating Peritoneal Metastasis of Gastric Cancer

Abstract

Peritoneal metastasis is a lethal manifestation of gastric cancer, with poor prognosis and limited treatment options. A targeted drug delivery system minimizing systemic toxicity is urgently needed. Given that platelets form stable aggregates with gastric cancer cells, we explored their feasibility as a drug carrier. We engineered paclitaxel-loaded platelets and assessed their antitumor efficacy using human gastric cancer cell lines. To evaluate therapeutic performance in vivo, a murine model of peritoneal metastasis was established with BALB/c-Slc-nu/nu mice. Paclitaxel was administered intraperitoneally at 25 mg/kg per week in both the free paclitaxel and paclitaxel-loaded platelets groups, via injection every 7 days for a total of 8 times. Paclitaxel-loaded platelets exhibited strong adhesion to gastric cancer cells, efficiently delivering paclitaxel intracellularly. Functional assays confirmed platelet activation capacity was preserved post drug loading. In vitro, paclitaxel-loaded platelets significantly inhibited tumor cell viability (p < 0.001). In vivo, they markedly reduced systemic drug exposure (p < 0.047) and significantly improved antitumor efficacy and survival versus free paclitaxel (p < 0.001). Our findings highlight platelets as a novel drug delivery system for peritoneal metastasis in gastric cancer. Leveraging their tumor-homing properties and biocompatibility, this approach enables targeted intraperitoneal chemotherapy, representing a promising strategy for this treatment-refractory disease.