Proanthocyanidin-Conjugated NIR-ΙΙ Nano-Prodrugs for Reversing Drug Resistance in Photothermal Therapy.

Targeting and multidrug resistance are the significant problems of current antitumor drugs, and these problems become the key factors in the design of nanomedicine. Herein, Au NRs and OPC-Au NPs were prepared via the hydroquinone seedless growth method and proanthocyanidin (OPC) one-pot method, and then pH-GSH-near-infrared ΙΙ (NIR-ΙΙ)-responsive nano-prodrugs Au/DOX-ss LNRs and OPC-Au/DOX-ss LNPs were designed by the encapsulation of doxorubicin prodrug DOX-ss with Au-S affinity and thermal-sensitive liposomes. Interestingly, OPC endowed OPC-Au NPs with reducibility and excellent performance in terms of particle size, zeta potential, encapsulation rate, and drug loading rate. In particular, the photothermal efficiencies of OPC-Au/DOX-ss LNPs increased to 59.22% under the 1064 nm NIR-ΙΙ irradiation. Compared with free DOX-ss and Lipid DOX-ss, the IC50 of OPC-Au/DOX-ss LNPs was decreased by 91.68% and 97.60%, respectively. Furthermore, the expression of P-gp in MCF-7/ADR was significantly inhibited (decreased by 65%). The potential of proanthocyanidin remodels the pH-GSH-NIR-ΙΙ responsiveness and drug resistance of OPC-Au/DOX-ss LNPs for breast cancer treatment in NIR-ΙΙ photodynamic/photothermal therapy.