药学学报, 2020, 55(1): 146-151
引用本文:
王谋, 胡英, 覃先燕, 龚涛, 张志荣, 符垚. 一种可用于黑色素瘤靶向递药的透明质酸纳米凝胶[J]. 药学学报, 2020, 55(1): 146-151.
WANG Mou, HU Ying, QIN Xian-yan, GONG Tao, ZHANG Zhi-rong, FU Yao. A hyaluronic acid nanogel for melanoma targeted drug delivery[J]. Acta Pharmaceutica Sinica, 2020, 55(1): 146-151.

一种可用于黑色素瘤靶向递药的透明质酸纳米凝胶
王谋, 胡英, 覃先燕, 龚涛, 张志荣, 符垚
四川大学华西药学院, 靶向药物与释药系统教育部重点实验室, 四川 成都 610041
摘要:
黑色素瘤恶性程度高,且发病率逐年上升。本研究制备了一种能特异性靶向黑色素瘤的透明质酸纳米凝胶,将巯基化的透明质酸修饰于表面功能化的普朗尼克F127-TPGS混合胶束制备共价交联的纳米凝胶。通过测定粒径考察其体外稳定性;细胞毒性实验考察该载体材料对细胞的毒性作用;细胞摄取实验定量和定性考察B16F10黑色素瘤细胞对该纳米凝胶的摄取情况。结果显示,本研究制备了一种30 nm左右的小粒径纳米凝胶,该纳米凝胶对小鼠3T3成纤维细胞与小鼠黑色素瘤B16F10细胞均无明显细胞毒性作用,与低表达CD44受体的3T3细胞相比,高表达CD44受体的B16F10细胞的摄取效率显著增加(P<0.05)。
关键词:    纳米凝胶      混合胶束      黑色素瘤      透明质酸      CD44     
A hyaluronic acid nanogel for melanoma targeted drug delivery
WANG Mou, HU Ying, QIN Xian-yan, GONG Tao, ZHANG Zhi-rong, FU Yao
Key Laboratory of Drug Targeting and Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Abstract:
Melanoma is a malignant tumor with a high degree of malignancy. The incidence of melanoma keeps increasing annually. In this study, a melanoma targeted hyaluronic acid (HA) nanogel was synthesized via crosslinking of thiolated HA with terminally functionalized F127-TPGS mixed micelles. Its stability in vitro was evaluated by the average particle size, and the cytotoxicity of the nanogel was investigated by in vitro cell based assays. Next, cell uptake studies were performed to quantitatively and qualitatively investigate the uptake of the nanogels in B16F10 cells. A small sized nanogel with a diameter of 30 nm was synthesized, which was proven to be minimally cytotoxic against both 3T3 or B16F10 cells. Compared with 3T3 cells with low levels of CD44, B16F10 cells with high levels of CD44 showed significantly higher cell uptake efficiency (P<0.05).
Key words:    nanogel    mixed micelle    melanoma    hyaluronic acid    CD44   
收稿日期: 2019-07-19
DOI: 10.16438/j.0513-4870.2019-0578
基金项目: 国家自然科学基金资助项目(81773654,81690261,81503018);四川大学优秀青年学者基金资助项目(2017SCU04A23);国家重点研究开发计划资助项目(2017YFC1104601);四川省青年科技创新研究团队基金资助项目(2016TD0001).
通讯作者: 符垚,Tel:86-28-85503798,E-mail:yfu4@scu.edu.cn
Email: yfu4@scu.edu.cn
相关功能
PDF(3729KB) Free
打印本文
0
作者相关文章
王谋  在本刊中的所有文章
胡英  在本刊中的所有文章
覃先燕  在本刊中的所有文章
龚涛  在本刊中的所有文章
张志荣  在本刊中的所有文章
符垚  在本刊中的所有文章

参考文献:
[1] Wang XY, He XF, Zhao FS, et al. Regulation gene expression of miR200c and ZEB1 positively enhances effect of tumor vaccine B16F10/GPI-IL-21 on inhibition of melanoma growth and metastasis[J]. J Transl Med, 2014, 12:68.
[2] Park SY, Song H, Sung MK, et al. Carnosic acid inhibits the epithelial-mesenchymal transition in B16F10 melanoma cells:a possible mechanism for the inhibition of cell migration[J]. Int J Mol Sci, 2014, 15:12698-12713.
[3] Zhao F, Zhang R, Wang J, et al. Effective tumor immunity to melanoma mediated by B16F10 cancer stem cell vaccine[J]. Int Immunopharmacol, 2017, 52:238-244.
[4] Schlesinger M, Roblek M, Ortmann K, et al. The role of VLA-4 binding for experimental melanoma metastasis and its inhibition by heparin[J]. Thromb Res, 2014, 133:855-862.
[5] Jing T, Li T, Ruan Z, et al. pHe-and glutathione-stepwise-responsive polypeptide nanogel for smart and efficient drug delivery[J]. J Mater Sci, 2018, 53:14933-14943.
[6] Liu L, Li T, Ruan Z, et al. Reduction-sensitive polypeptide nanogel conjugated BODIPY-Br for NIR imaging-guided chem/photodynamic therapy at low light and drug dose[J]. Mater Sci Eng C, 2018, 92:745-756.
[7] Gokila S, Gomathi T, Vijayalakshmi K, et al. Development of 3D scaffolds using nanochitosan/silk-fibroin/hyaluronic acid biomaterials for tissue engineering applications[J]. Int J Biol Macromol, 2018, 120:876-885.
[8] Luo P, Liu L, Xu W, et al. Preparation and characterization of aminated hyaluronic acid/oxidizedhydroxyethyl cellulose hydrogel[J]. Carbohyd Polym, 2018, 199:170-177.
[9] Hanoux V, Eguida J, Fleurot E, et al. Increase in hyaluronic acid degradation decreases the expression of estrogen receptor alpha in MCF7 breast cancer cell line[J]. Mol Cell Endocrinol, 2018, 476:185-197.
[10] Shi S, Zhou M, Li X, et al. Synergistic active targeting of dually integrin alphavbeta3/CD44-targeted nanoparticles to B16F10 tumors located at different sites of mouse bodies[J]. J Control Release, 2016, 235:1-13.
[11] Gu J, Chen X, Ren X, et al. CD44-targeted hyaluronic acid-coated redox-responsive hyperbranched poly(amido amine)/plasmid DNA ternary nanoassemblies for efficient gene delivery[J]. Bioconjug Chem, 2016, 27:1723-1736.
[12] Lima-Sousa R, de Melo-Diogo D, Alves CG, et al. Hyaluronic acid functionalized green reduced graphene oxide for targeted cancer photothermal therapy[J]. Carbohyd Polym, 2018, 200:93-99.
[13] Wang Y, Gong T, Zhang Z, et al. Matrix stiffness differentially regulates cellular uptake behavior of nanoparticles in two breast cancer cell lines[J]. ACS Appl Mater Interfaces, 2017, 9:25915-25928.
[14] Deng C, Zhang Q, Fu Y, et al. Coadministration of oligomeric hyaluronic acid-modified liposomes with tumor-penetrating peptide-iRGD enhances the antitumor efficacy of doxorubicin against melanoma[J]. ACS Appl Mater Interfaces, 2017, 9:1280-1292.
[15] Huang AW, Zhao JL, Liu ZH, et al. Preparation and evaluation of insulin thiolated hyaluronic acid nanoparticles in vitro[J]. Chin J Biochem Pharm (中国生化药物杂志), 2014, 7:78-80.
[16] Cao X, Zhou X, Wang Y, et al. Diblock-and triblock-copolymer based mixed micelles with high tumor penetration in vitro and in vivo[J]. J Mater Chem B, 2016, 4:3216-3224.
[17] Choi SK, Park S, Jang S, et al. Cascade regulation of PPARgamma(2) and C/EBPalpha signaling pathways by celastrol impairs adipocyte differentiation and stimulates lipolysis in 3T3-L1 adipocytes[J]. Metabolism, 2016, 65:646-654.
[18] Sapudom J, Ullm F, Martin S, et al. Molecular weight specific impact of soluble and immobilized hyaluronan on CD44 expressing melanoma cells in 3D collagen matrices[J]. Acta Biomater, 2017, 50:259-270.