Multifunctional amino acid-based nanoparticles for sequential drug delivery to overcome multidrug resistant cancer.

Fiche publication

Date publication

avril 2026

Journal

Journal of controlled release : official journal of the Controlled Release Society

Auteurs

Membres identifiés du Cancéropôle Est :
Dr MENARD-MOYON Cécilia , Dr BIANCO Alberto

Tous les auteurs :
Wang T, Sang N, Ménard-Moyon C, Miyako E, Bianco A

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/42036031

Résumé

Multidrug resistance (MDR), often emerging after chemotherapy, has long restricted the therapeutic efficacy of cancer treatment in clinical practice. Among the various strategies developed to overcome MDR, the sequential delivery of P-glycoprotein inhibitors and anticancer drugs has shown great promise when compared with traditional co-delivery approaches. In this work, porous amino acid nanoparticles (NPs) are fabricated via a self-templating method and loaded with doxorubicin (Dox). NPs are coated with polydopamine (PDA), which is functionalized with quinidine, a P-glycoprotein inhibitor, via a pH-sensitive linker. The pH/glutathione (GSH) sensitivity of PDA allows a delayed release of Dox compared to quinidine, thereby enabling a sequential drug delivery. Specifically, the release profile of Dox enables to be precisely controlled through adjusting the number of the PDA layer. In addition, the incorporation of PDA imparts photothermal capabilities to NPs, allowing for their use in synergistic photothermal therapy (PTT) and chemotherapy. Finally, the antitumor effect of NPs is evaluated in vitro and in vivo. The viability of MDR EMT-6/AR1 cells is decreased to less than 5% after the treatment with NPs and a significant tumor regression is observed in MDR tumor-bearing mice after combining PTT and chemotherapy, providing a high antitumor efficacy.