文献类型：期刊文献

英文题名：Bioactive Core-Shell Hydroxyapatite Nanoplatform for Overcoming Multidrug Resistance in Cancer Therapy via Tumor-Specific Synergistic Calcium Overload

作者：Zhang, Shuiquan[1]; Shen, Tao[2]; Zhang, Wen[2]; Gong, Xue[2]; Yuan, Yuan[1]; Liu, Changsheng[1]; Qian, Jiangchao[2]

机构：[1] Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Center for Biomedical Materials of the Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, China; [2] The State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China

年份：2025

外文期刊名：SSRN

收录：EI(收录号：20250550793)

语种：英文

外文关键词：Bioactivity - Biocompatibility - Biomineralization - Calcification (biochemistry) - Calcium - Cell death - Chemical activation - Chemotherapy - Diseases - Microfluidics - Oncology - Platinum compounds - Targeted drug delivery - Tumors

摘要：Cancer remains the second leading cause of death worldwide, with over 90% of cancer-related mortality attributed to multidrug resistance (MDR). While calcium overload-based therapies have shown promise, their clinical translation is hindered by poor tumor selectivity. Hydroxyapatite nanoparticles (HAPNs), excellent biocompatible biomaterials, possess intrinsic bioactivity to induce tumor-specific calcium overload and apoptosis in various cancer cells including MDR tumor cells. Herein, a tumor-specific calcium overload strategy based on the synergistic action of HAPNs and chemotherapy drugs is developed to overcome MDR. For the first time, uniform core-shell hydroxyapatite nanoparticles (CSHNs) with selective cytotoxicity to cancer cells are synthesized via microfluidic-assisted mineralization using PEGBC-DGSE-PEGBC (PDP) nanomicelles as soft templates. Further hyaluronic acid (HA) modification yields a monodisperse bioactive nanoplatform CSHN@HA with enhanced tumor targeting and nuclear delivery efficiency. To further amplify calcium overload, artemisinin (Art), an antimalarial drug and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase inhibitor, is selected and encapsulated into CSHN@HA to construct Art@CSHN@HA. CSHN@HA alone induces calcium overload and exhibits intrinsic antitumor activity. When combined with Art, they synergistically enhance calcium overload, mitochondrial damage, ATP depletion, activation of both extrinsic and intrinsic apoptotic pathways in cancer cells, thereby effectively reversing MDR. In vivo, Art@CSHN@HA completely inhibits A549/PTX tumor growth while selectively inducing tumor calcification. This work demonstrates a clinically translatable bioactive nanoplatform that integrates precise tumor targeting, synergistic calcium overload amplification, and MDR reversal, offering a safe and effective strategy for cancer therapy. ? 2025, The Authors. All rights reserved.