The morphology of hydroxyapatite nanoparticles regulates clathrinmediated endocytosis in melanoma cells and resultant anti-tumor efficiency  

作　　者：Hongfeng Wu Yuchen Hua Jinjie Wu Qin Zeng Xiao Yang Xiangdong Zhu Xingdong Zhang 

机构地区：[1]National Engineering Research Center for Biomaterials,Sichuan University,Chengdu 610064,China [2]NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterials&Institute of Regulatory Science for Medical Devices&NMPA Research Base of Regulatory Science for Medical Devices,Sichuan University,Chengdu 610064,China [3]Research Center for Materials Genome Engineering,Sichuan University,Chengdu 610064,China

出　　处：《Nano Research》2022年第7期6256-6265,共10页纳米研究（英文版）

基　　金：supported by Sichuan Science and Technology Program(No.2020YFS0039);the National Natural Science Foundation of China(No.81901685);the Fundamental Research Funds for the Central Universities(No.YJ201915).

摘　　要：Clathrin-mediated endocytosis plays a critical role for hydroxyapatite nanoparticles(HANPs)to enter tumor cells,induce mitochondrial apoptosis,and inhibit tumor growth.This study was aimed to investigate how the morphology of HANPs impacts the endocytosis of the particles in melanoma cells,and their anti-tumor effect by using in vitro cell experiments and in vivo tumor animal model.Three shapes of HANPs,including granular HANPs(G-HANPs),rod-like HANPs(R-HANPs),and needle-like HANPs(N-HANPs),were successfully prepared by wet chemical method.All the three HANPs could be internalized into A375 melanoma cells as indicated by cellular transmission electron microscopy images.Among these HANPs,only G-HANPs induced morphological change of mitochondria and loss of mitochondrial membrane potential(Δψm),and exhibited the greatest intracellular internalization efficiency in the tumor cells.Furthermore,the results of immunofluorescence staining and western blotting indicated that the level of adaptin-2(AP2)protein was up-regulated by all the HANPs,and highest in G-HANPs treated A375 cells.Moreover,in the tumor-bearing mouse model,we found that tumor growth was delayed by all the three HANPs,of which,G-HANPs delayed tumor growth most efficiently and presented a highest expression level of AP2 protein in tumor tissues.Therefore,this study suggested that the morphology of HANPs regulated their endocytosis efficiency and their effect to inhibit tumor growth.This work facilitates to direct the rational design of nano-materials for tumor therapy.

关 键 词：hydroxyapatite nanoparticles adaptin-2 protein MORPHOLOGY ENDOCYTOSIS anti-tumor effect 

分 类 号：TB3[一般工业技术—材料科学与工程] R318.08[医药卫生—生物医学工程]