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Microenvironment-responsive size-adaptive nanoparticles: hyaluronidase/acid/NIR light activation for deep-penetration
Hao Wu1,2, Hongping Li1, Li Li1
1Engineering Research Center for Pharmaceuticals and Equipments of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, 610106, PR China.
None:
The dense tumor microenvironment (TME) hinders drug delivery. Herein, we report hyaluronidase (HAase)/acid/near-infrared (NIR) light-responsive, size-adaptive nanoparticles (NPs) co-loaded with doxorubicin (DOX) and IR780 (IDHNs). IDHNs integrate dual targeting with size-fissile capability: biocompatible human serum albumin (HSA) prolongs circulation; while hyaluronic acid (HA) enables CD44-mediated accumulation and HAase-triggered fission reduces particle size, facilitating deep stromal penetration. Acidic TME and NIR laser irradiation further accelerates drug release, achieving potent chemo-photothermal/photodynamic synergy. In vitro and in vivo studies confirm that IDHNs surpass monotherapies in precision, efficacy, and safety. This trimodal nanoplatform provides a versatile strategy to overcome physical TME barriers and advance tumor-targeted therapy.
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