Dual-drug nanomedicine with hydrophilic F127-Modified magnetic nanocarriers assembled in amphiphilic gelatin for enhanced penetration and drug delivery in deep tumor tissue

Introduction: Deep penetration of large-sized drug nanocarriers into tumors is important to improve the efficacy of tumor therapy. Methods: In this study, we developed a size-changeable “Trojan Horse” nanocarrier (THNC) composed of paclitaxel (PTX)-loaded Greek soldiers (GSs; ~20 nm) assembled in an amphiphilic gelatin matrix with hydrophilic losartan (LST) added. Results: With amphiphilic gelatin matrix cleavage by matrix metalloproteinase-2, LST showed fast release of up to 60% accumulated drug at 6 h, but a slow release kinetic (~20%) was detected in the PTX from the GSs, indicating that THNCs enable controllable release of LST and PTX drugs for penetration into the tumor tissue. The in vitro cell viability in a 3D tumor spheroid model indicated that the PTX-loaded GSs liberated from THNCs showed deeper penetration as well as higher cytotoxicity, reducing a tumor spheroid to half its original size and collapsing the structure of the tumor microenvironment. Conclusion: The results demonstrate that the THNCs with controlled drug release and deep penetration of magnetic GSs show great potential for cancer therapy.