文献类型：期刊文献

英文题名：Safe, simple and multifunctional hydroxyapatite nanoparticles for efficient overcoming of tumor multidrug resistance

作者：Shen, Tao[1];Wang, Hao[1];Zhang, Shuiquan[2,3];Dong, Xiulin[1];Zhang, Wen[1];Liu, Changsheng[4];Qian, Jiangchao[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Key Lab Ultrafine Mat Minist Educ, Engn Res Ctr Biomed Mat Minist Educ, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Sch Mat Sci & Engn, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Key Lab Ultrafine Mat, Minist Educ, Shanghai 200237, Peoples R China

年份：2024

卷号：40

外文期刊名：APPLIED MATERIALS TODAY

收录：;EI(收录号：20243416927200);WOS:【SCI-EXPANDED(收录号:WOS:001302216200001)】；

基金：This work was financially supported by the National Key Research and Development Program of China (2020YFA0908900) , the National Natural Science Foundation of China (31871011) , and the Innovative Research Group Project of the National Natural Science Foundation of China (51621002) .

语种：英文

外文关键词：Hydroxyapatite nanoparticles; Chemotherapeutic drugs; Multidrug resistance reversal; Synergistic effects; Multiple drug-resistant cells

摘要：Multidrug resistance (MDR) of cancer is the most common obstacle to chemotherapy. Many complex multifunctional nanoparticles have been developed for combination of two or more therapeutics to overcome MDR. Unlike these sophisticated nanoparticles, hydroxyapatite nanoparticles (HAPNs) were found to be able to inhibit cell proliferation of various human cancer cells. Herein, with different MDR cells and chemotherapeutic drugs, we tested whether HAPNs can be widely applied in fighting cancer drug resistance. Rod-shaped HAPNs were synthesized by the aqueous precipitation and then successfully loaded with paclitaxel (PTX) and doxorubicin (DOX) by physical adsorption to obtain pH-responsive drug-loaded nanoparticles, PHAPNs and DHAPNs, respectively. Plain HAPNs exhibited selective cytotoxicity to drug-resistant breast cancer cells MCF-7/ADR, lung cancer cells H69AR and A549/PTX, while spared normal human liver cells L-02. HAPN treatment led to an increase in the apoptosis ratio, a decrease in cell viability and a sustained increase in intracellular calcium ion level in MDR cells. Furthermore, HAPNs facilitated the delivery and accumulation of both drugs, thereby improving the DOX-induced DNA damage in H69AR cells, as well as the acetylation of alpha-tubulin and cell cycle arrest led by PTX in MCF-7/ADR and A549/PTX cells. Drug-loaded HAPNs greatly enhanced mitochondrial damage, inhibited ATP synthesis and efflux pump activity, and triggered both the intrinsic and extrinsic apoptosis induced by HAPNs or drugs alone. HAPNs acted synergistically with DOX and PTX, resulting in a >6fold reduction in the IC50 compared with free drugs for these MDR cells. Notably, PHAPNs successfully suppressed the tumor growth in A549/PTX xenograft mice and exhibited excellent biocompatibility in vivo. These findings demonstrated that HAPNs may be widely utilized to reverse the resistance of various drug-resistant cells, providing a simple but practical approach to overcome MDR of cancer.