Construction of a Novel Nanoparticulate Drug Co-Delivery System for Two Active Components of Traditional Chinese Medicine and Its In Vitro and In Vivo Quality Evaluation

Background: Co-delivery of two drugs with diverse physicochemical properties and a specific administration sequence holds great importance in cancer theranostics to overcome drug resistance and reduce side effects. Paclitaxel (PTX) and hydroxycamptothecin (HCPT) have long been used clinically as chemotherapeutic agents for Nasopharyn-geal carcinoma (NPC). However, their clinical application is severely restricted by low water solubility, poor stability, and systemic adverse reactions. Nanoparticle-based drug delivery systems provide a promising platform for combination cancer therapy. Methods: In this study, folic acid-modified and dual drug-loaded self-assembled HCPT/PTX@FA@p-PS-SPIONs were successfully fabricated via the emulsification–solvent evaporation method using amphiphilic phosphorylated polystyrene (p-PS). The characterization, cellular uptake, and in vivo pharmacokinetic profiles of the nanoparticles in NPC models were systematically investigated. Result: HCPT/PTX@FA@p-PS-SPIONs were successfully prepared with p-PS as the copolymer backbone. The nanoparticles exhibited a uniform particle size of 196.9 ± 5.5 nm and a zeta potential of −7.3 ± 0.7 mV. The encapsulation efficiency (EE) was 81.4 ± 2.5% for PTX and 67.6 ± 4.1% for HCPT. The drug loading (DL) efficiency was 18.4 ± 1.5% for PTX and 12.2 ± 1.0% for HCPT. HCPT/PTX@FA@p-PS-SPIONs showed favorable biocompatibility. Sustained and sequential release of the two drugs contributed to an enhanced therapeutic effect. Moreover, under magnetic field (MF) guidance, HCPT/PTX@FA@p-PS-SPIONs exhibited stronger inhibitory effects on NPC cells than single-drug, cocktail, or dual-drug groups, demonstrating the superiority of the combined therapy. Pharmacokinetic studies in rats revealed that the half-lives of PTX and HCPT were 3.9 ± 1.2 h and 4.7 ± 1.1 h, respectively, confirming that HCPT/PTX@FA@p-PS-SPIONs could resist rapid metabolism and clearance in vivo. Conclusions: The long-circulating, folic acid-targeted nanoparticles HCPT/PTX@FA@p-PS-SPIONs show great potential for the targeted therapy of nasopharyngeal carcinoma.