Dual-stimuli magnetic drug nanoparticles for chemoimmunotherapy: Magnetically driven, charge-reversal enhanced tumour penetration and pH-triggered drug release

Feng, Xue, Wang, Hongdi, Xue, Yuxiang, Ozgultekin, Nurbanu, Kitamura, Takanori, Li, Jin ORCID: https://orcid.org/0000-0002-4672-6806, Ouyang, Defang, Zhu, Guangyu, Mao, Guangzhao, Qian, Bin-Zhi and Chen, Xianfeng 2026. Dual-stimuli magnetic drug nanoparticles for chemoimmunotherapy: Magnetically driven, charge-reversal enhanced tumour penetration and pH-triggered drug release. Chemical Engineering Journal 532 , 174177. 10.1016/j.cej.2026.174177

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Abstract

Poor intratumoral penetration remains a major obstacle to effective chemotherapy, caused by dense extracellular matrices, high interstitial pressure, and abnormal vasculature. Magnetic nanoparticle (NP)-mediated drug delivery provides spatial control, but existing systems suffer from low drug loading, weak responsiveness to tumour microenvironments, and limited penetration. Here, we report for the first time a self-assembled nanoplatform in which ultrasmall Fe₃O₄ NPs are evenly distributed within a carrier-free doxorubicin (DOX) core and surface-modified with glycol chitosan (Fe₃O₄-DOX@GC NPs). This unique architecture simultaneously achieves ultra-high drug loading (69%) and markedly enhances responsiveness to external magnetic fields, addressing two long-standing challenges in magnetic nanomedicine. In addition, tumour acidity triggers a surface charge reversal from negative to positive, promoting efficient cellular uptake. In 3D tumour spheroids, dual static and alternating magnetic fields increased DOX retention by 2.02-fold compared with static fields alone. In vivo, magnetic guidance produced a 6.3-fold increase in tumour accumulation and a 58% tumour volume reduction relative to free DOX. Importantly, the nanoplatform also activated antitumour immunity, significantly expanding cytotoxic T cells and antitumoral macrophages. This first-in-class dual chemotherapeutic–immunotherapeutic nanoplatform establishes a powerful strategy to overcome tumour penetration barriers while reshaping the immune microenvironment for improved cancer therapy.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Engineering
Publisher:	Elsevier BV
ISSN:	1385-8947
Date of First Compliant Deposit:	2 March 2026
Date of Acceptance:	13 February 2026
Last Modified:	02 Mar 2026 13:00
URI:	https://orca.cardiff.ac.uk/id/eprint/185374

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