Preparation and Antitumor Evaluation of Four Pentacyclic Triterpenoids and 10-Hydroxycamptothecin Self-Assembled Nanoparticles

<b>Background/Objectives</b>: A carrier-free self-assembled nanomedicine delivery system refers to a high drug-loading nanomedicine delivery system prepared by one or more active drug ingredients through supramolecular self-assembly, which has the advantages of high drug-loading and a simple preparation process, enabling multidrug synergistic therapy. 10-hydroxycamptothecin (HCPT) have active antitumor effects. Pentacyclic triterpenes are natural active components with a wide range of pharmacological activities. This study aimed to investigate the impact of structural types on the self-assembly of pentacyclic triterpenes and HCPT. <b>Methods</b>: Molecular docking studies were performed. Self-assembled nanoparticles were designed by co-assembling ursolic acid (UA), asiatic acid (AA), oleanic acid (OA), and betulinic acid (BA) with HCPT via anti-solvent precipitation combined with ultrasonication, followed by characterization. Cytotoxicity assays using the CCK-8 method revealed that the prepared self-assembled nanoparticles exhibited concentration-dependent inhibitory effects against A375, AGS, HCT-116, and HepG2 tumor cells. Confocal laser scanning microscopy (CLSM) indicated that UA/HCPT nanoparticles (UA/HCPT-NPs) were more efficiently internalized and accumulated in cells compared with the UA + HCPT physical mixture. <b>Results</b>: Both in vitro and in vivo results demonstrated that the self-assembled nanoparticles significantly enhanced antitumor efficacy while exerting minimal toxicity on major organs within the tested dose range. <b>Conclusions</b>: In summary, these findings highlight that pentacyclic triterpenoids components possess significant self-assembly potential, and that dual-drug co-delivery via self-assembled nanoparticles represents as a promising strategy for cancer therapy.