Stable Porous Organic\nCage Nanocapsules for pH-Responsive\nAnticancer Drug Delivery for Precise Tumor Therapy

The search for drug\nnanocarriers with stimuli-responsive properties\nand high payloads for targeted drug delivery and precision medicine\nis currently a focal point of biomedical research, but this endeavor\nstill encounters various challenges. Herein, a porous organic cage\n(POC) is applied to paclitaxel (PTX) drug delivery for cancer therapy\nfor the first time. Specifically, water-soluble, stable, and biocompatible\nPOC-based nanocapsules (PTX@POC@RH40) with PTX encapsulation efficiency\nover 98% can be synthesized by simply grafting nonionic surfactant\n(Polyoxyl 40 hydrogenated castor oil, RH40) on the POC surface. These\nPTX@POC@RH40 nanocapsules demonstrate remarkable stability for more\nthan a week without aggregation and exhibit pH-responsive behavior\nunder acidic conditions (pH 5.5) and display sustained release behavior\nat both pH 7.4 and pH 5.5. Intravenous administration of PTX@POC@RH40\nled to a 3.5-fold increase in PTX bioavailability compared with the\nfree PTX group in rats. Moreover, in vivo mouse model experiments\ninvolving 4T1 subcutaneous breast cancer tumors revealed that PTX@POC@RH40\nexhibited enhanced anticancer efficacy with minimal toxicity compared\nwith free PTX. These findings underscore the potential of POCs as\npromising nanocarriers for stimuli-responsive drug delivery in therapeutic\napplications.