Microenvironment-responsive size-adaptive nanoparticles: hyaluronidase/acid/NIR light activation for deep-penetration trimodal therapy
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. <i>In vitro</i> and <i>in vivo</i> 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.
Authors
- Shuai Luo (ORCID: https://orcid.org/0000-0003-1423-9779)
- Jing Tao (ORCID: https://orcid.org/0000-0002-9746-4391)
- Xue Shen (ORCID: https://orcid.org/0000-0002-7145-7601)
- Ling Mei (ORCID: https://orcid.org/0000-0002-2762-2235)
- Hao Wu (ORCID: https://orcid.org/0000-0003-1262-5932)
- Hongping Li (ORCID: https://orcid.org/0000-0002-4332-7543)
- Yung‐Chang Chen (ORCID: https://orcid.org/0000-0001-5777-5948)
- Wenhao Li (ORCID: https://orcid.org/0000-0003-2614-0768)
- Lin Ye (ORCID: https://orcid.org/0000-0003-0062-6436)
- Li Zhu (ORCID: https://orcid.org/0000-0001-5249-6536)
- Gang He (ORCID: https://orcid.org/0000-0002-8660-6091)
- Chengyong Shi (ORCID: https://orcid.org/0000-0002-8830-9357)
- Hongping Yang
- Li Li (ORCID: https://orcid.org/0000-0001-5324-2271)
Institutions
- Sichuan Cancer Hospital (CN)
- Chengdu University (CN)
- Chengdu University of Traditional Chinese Medicine (CN)
Publication Details
- Journal
- Materials Today Bio
- Published
- 2025-10-09
- DOI
- https://doi.org/10.1016/j.mtbio.2025.102384
- Primary Topic
- Nanoparticle-Based Drug Delivery
- Type
- article
- Field-Weighted Citation Impact
- 0.00