Nanoparticle-Based Therapy for Multidrug-Resistant Cancer via Dual Modulation of P-Glycoprotein and the Tumor Microenvironment
발표자
최화경 (가톨릭대학교 성심교정)
연구책임자
김경섭 (가톨릭대학교 성심교정)
공동저자
김경섭 (가톨릭대학교 성심교정), 최화경 (가톨릭대학교 성심교정)
초록
내용
We present a liposomal nanoplatform, termed the multidrug-resistant nanoparticle (MDRP), designed to address cancer multidrug resistance (MDR). MDRP co-delivers pantoprazole (PZ) and paclitaxel (PTX), targeting the acidic tumor microenvironment while suppressing P-glycoprotein (P-gp) and vacuolar-type ATPase (V-ATPase). PZ rapidly releases within 12 hours, neutralizing pH to inhibit drug efflux, whereas PTX provides sustained cytotoxicity over 48 hours. In vitro, MDRP enhanced uptake and cytotoxicity in P-gp-expressing (MCF-7/mdr, UV-2237M) and non-expressing (MCF-7, MDA-MB-231) cells, reducing IC50 values by 10.5-fold. In vivo, a single systemic administration induced complete remission in 80% of fibrosarcoma-bearing mice without weight loss or organ toxicity. MDRP also elevated dendritic cell maturation and cytotoxic T cell levels, suggesting immune activation. These results highlight MDRP as a promising strategy for reversing MDR and achieving tumor remission.