文献类型：期刊文献

英文题名：Synergistic Combination of Bioactive Hydroxyapatite Nanoparticles and the Chemotherapeutic Doxorubicin to Overcome Tumor Multidrug Resistance

作者：Dong, Xiulin[1];Sun, Yi[1];Li, Yuanyuan[1];Ma, Xiaoyu[2];Zhang, Shuiquan[2];Yuan, Yuan[2];Kohn, Joachim[3];Liu, Changsheng[2];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, Frontiers Sci Ctr Materiobiol & Dynam Chem, Shanghai 200237, Peoples R China;[3]Rutgers State Univ, New Jersey Ctr Biomat, Dept Chem & Chem Biol, Piscataway, NJ 08855 USA

年份：2021

卷号：17

期号：18

外文期刊名：SMALL

收录：;EI(收录号：20211310128060);WOS:【SCI-EXPANDED(收录号:WOS:000631826600001)】；

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 Ministry of Education of China (111 Project, B14018).

语种：英文

外文关键词：anti‐ tumor activity; bioactivity; hydroxyapatite nanoparticles; mitochondrial Ca; (2+) overload; multidrug resistance reversal

摘要：Multidrug resistance (MDR) is one of the biggest obstacles in cancer chemotherapy. Here, a remarkable reversal of MDR in breast cancer through the synergistic effects of bioactive hydroxyapatite nanoparticles (HAPNs) and doxorubicin (DOX) is shown. DOX loaded HAPNs (DHAPNs) exhibit a 150-fold reduction in IC50 compared with free DOX for human MDR breast cancer MCF-7/ADR cells, and lead to almost complete inhibition of tumor growth in vivo without obvious side effects of free DOX. This high efficacy and specificity could be attributed to multiple action mechanisms of HAPNs. In addition to acting as the conventional nanocarriers to facilitate the cellular uptake and retention of DOX in MCF-7/ADR cells, more importantly, drug-free HAPNs themselves are able to prevent drug being pumped out of MDR cells through targeting mitochondria to induce mitochondrial damage and inhibit ATP production and to trigger sustained mitochondrial calcium overload and apoptosis in MDR cancer cells while not affecting normal cells. The results demonstrate that this simple but versatile bioactive nanoparticle provides a practical approach to effectively overcome MDR.