Overcoming chemoresistance via NO-mediated HSP inhibition using hybrid membrane-coated multifunctional nanoplatforms

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Chemotherapy resistance and imprecise drug delivery are significant hurdles in cancer treatment.
• Heat shock proteins (HSPs) are implicated in chemotherapy resistance, necessitating novel therapeutic strategies.
• Current treatments often lack specificity, leading to off-target toxicity.

Purpose of the Study:

• To develop a multifunctional nanoparticle system for enhanced cervical cancer treatment.
• To overcome chemotherapy resistance by targeting heat shock proteins (HSPs).
• To achieve precise drug delivery and controlled release using a biomimetic nanoplatform.

Main Methods:

• Development of a hybrid biomimetic nanoparticle (CuS-PTX-ICG-L-arg@HR) integrating photothermal therapy (PTT), chemotherapy, and gas therapy.
• Utilizing red blood cell and HeLa cell membranes for immune evasion, tumor targeting, and improved pharmacokinetics.
• Implementing a light-activated nitric oxide (NO) generation strategy using L-arginine (L-arg) to inhibit HSPs under near-infrared (NIR) irradiation.

Main Results:

• The nanoparticle system demonstrated enhanced accumulation and circulation time in tumors.
• The NO generation strategy successfully inhibited HSPs, reversing paclitaxel (PTX) resistance in tumors.
• Copper sulfide (CuS) nanoparticles facilitated light-triggered drug release and localized photothermal effects.

Conclusions:

• This study presents a novel approach to overcome chemotherapy resistance via NO-mediated HSP inhibition.
• The developed nanoplatform significantly improves the efficacy of paclitaxel in drug-resistant cervical cancer.
• This multifunctional system offers a promising strategy for advancing precision cancer therapy and drug delivery.