Reversal of drug resistance in breast cancer cells by photodynamic action mediated by curcumin/Ko143/PLGA nanoparticles

Abstract

Objective: The objective of this study is to prepare Cur/Ko143/PLGA that encapsulate the photosensitizer curcumin (Cur) and the multidrug transporter-specific inhibitor Ko143 to investigate its application in reversing drug resistance in breast cancer and evaluate its properties and therapeutic efficacy. Results: After successful preparation of nanoparticles, the encapsulation rate of Cur/Ko143/PLGA was 73.8% ± 1.8%, and the drug loading rate was 2.8% ± 0.1%. The Cur/Ko143/PLGA were spherical and regular in morphology under transmission electron microscopy. The nanoparticles were morphologically intact, were uniform in size, and did not show significant aggregation under scanning electron microscopy. The average particle size of Cur/Ko143/PLGA was 232.32 ± 10.60 nm, the polymer dispersion index was 0.01, and the zeta potential was −17.25 ± 0.65 mV, as determined by laser particle sizing. In vitro ultrasound observation showed that Cur/Ko143/PLGA were enhanced in both the B-mode and contrast modes. Intracellular Cur fluorescence detection, biocompatibility testing, cell scratch experiment, flow detection of apoptosis, live–dead staining, and actin polymerization test all prove that new nanomaterials have better photodynamic efficacy. Conclusion: Drug-carrying Cur/Ko143/PLGA nanoparticles can increase the concentration of the intracellular photosensitizer Cur and increase the photodynamic efficacy by inhibiting an efflux pump, which is expected to become a new therapeutic strategy.