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A drug reservoir strategy for long-acting cancer therapy using morphologically transformed amphiphilic polymeric nanoparticles

Sun, Jiao, Wang, Yiqing, Zhang, Jiaxing, Wang, Jianhao, Wang, Cheng·2025·Acta Biomaterialia
DOI 10.1016/j.actbio.2025.07.006
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Abstract

The effective accumulation of drugs within tumor tissues is impeded by extracellular barriers, necessitating repeated dosing in cancer therapy. However, repeated dosing can trigger the accelerated blood clearance (ABC) effect, resulting in limited therapeutic efficacy. Herein, in this study, a drug reservoir strategy was proposed to solve this dilemma, using an amphiphilic polymer (LPHF) with tunable hydrophilicity and morphology transformation capabilities. At pH 7.4, LPHF with balanced hydrophilicity can self-assemble into nanoparticles and be loaded with Dox (LPHF@Dox). At pH 6.5, LPHF@Dox with reduced hydrophilicity undergoes an immediate transition from a dispersed state to a deposited state, which can serve as a tumor-specific drug reservoir. Under the weakly acidic tumor microenvironment, the amide with adjacent carboxylic acid groups in LPHF exhibits pH-dependent hydrolysis, leading to a reversion of LPHF to a hydrophilic state and reconstitution into nanoparticles (LPHF@Dox RC ). The resulting LPHF@Dox RC undergoes charge reversal to a positive state, which coordinated with conjugated folic acid, to synergistically improves both the cellular internalization and tumor penetration of LPHF@Dox RC . This intelligent amphiphilic polymer, functioning as a tumor-specific drug reservoir, may provide a new approach for effective cancer treatment. STATEMENT OF SIGNIFICANCE: This study introduces a pH-responsive polymeric nanoparticle (LPHF) that transforms into a tumor-specifi…

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Metadata

Authors
Sun, J., Wang, Y., Zhang, J., Wang, J., & Wang, C.
Venue
Acta Biomaterialia
Publisher
Elsevier BV
Published
2025-08
Volume
202
Pages
435-449
ISSN
1742-7061
DOI
10.1016/j.actbio.2025.07.006
Cited by
7
References
0
Language
en
Licence
Funders
  • Graduate Research and Innovation Projects of Jiangsu Province (KYCX23_3033)
  • Soochow University (KJS2104)
  • Jiangsu Provincial Department of Education (21KJD350003)

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