Authors
Ruoyu Cheng, Zehua Liu, Gang Zhao, Han Gao, Wei Huang, Baoding Zhang, Zheng Wang, Jiachen Li, Junyuan Xiao, Yuting Fan, Fuhua Zhang, Jouni Hirvonen, Xianming Deng, Hélder A Santos, Wenguo Cui
Published in
Materials today. Bio. Volume 40. Pages 103545. Epub Aug 10, 2026.
Abstract
Phosphoinositide kinase containing FYVE-type zinc finger (PIKfyve) inhibitors show potential immunomodulatory activity but suffer from poor tumor targeting and formulation challenges. Herein, we screened a series of PIKfyve inhibitors and engineered selected PIKfyve inhibitor into amorphous metal-drug frameworks (aMDFs) through coordination chemistry between pyridine/imidazole moieties and tailored metal nodes verified by theoretical simulations and nuclear magnetic resonance spectroscopy. The resulting aMDFs showed enhanced stability and processability, enabling efficient encapsulation into solid lipid NPs (HF@SLN). In both orthotopic and subcutaneous murine pancreatic cancer models, HF@SLN demonstrated superior tumor growth inhibition over free PIKfyve inhibitors. HF@SLN treatment was associated with increased transcription factor EB (TFEB) expression, accompanied by enhanced cytotoxic T cell infiltration and improved antitumor immune responses in both murine and human pancreatic tumor samples. This study demonstrates the feasibility of employing carrier-free aMDFs for the formulation and delivery of pyridine- and imidazole-containing therapeutics.
PMID:
42633183
Bibliographic data and abstract were imported from PubMed on 23 Aug 2026.
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