Novel Insights into Combating Cancer Chemotherapy Resistance Using a Plasmonic Nanocarrier: Enhancing Drug Sensitiveness and Accumulation Simultaneously with Localized Mild Photothermal Stimulus of Femtosecond Pulsed Laser

Chemotherapy resistance remains a large obstacle to successful clinical cancer therapy, mainly due to little accumulation and low sensitivity of drugs and the effective clinical strategy still lacks. Herein, a novel yet simple strategy to combat cancer drug resistance using the plasmonic feature‐based photothermal properties is reported. Rather than directly killing cancer cells using nanoparticle‐mediated hyperthermia, for the first time, localized plasmonic heating of gold nanorod at a mild laser power density can modulate the drug‐resistance related genes. This photothermal effect triggers higher expression of heat shock factor (HSF‐1) trimers and depresses the expression of P‐glycoprotein (Pgp) and mutant p53. In turn, both drug accumulation in the breast cancer resistant cells (MCF‐7/ADR) and their sensitiveness to drugs can be greatly enhanced. Considering the universality and feasibility of this strategy, it points out a new unique way to challenge drug resistance.