激光生物学报, 2020, 29 (6): 550, 网络出版: 2021-02-05  

基于装载白藜芦醇的脂质体包裹介孔碳纳米管用于靶向及近红外激光触发的化疗 /光热协同肿瘤治疗

Liposome Coated Mesoporous Carbon Nanotube with Resveratrol Loading for Targeted and Near-infrared Laser-triggered Chemo/Photothermal Synergistic Cancer Therapy
作者单位
1 湖南省人民医院老年医学研究所,长沙 410016
2 中南大学肿瘤研究所,长沙 410078
摘要
为解决白藜芦醇(Res)因水溶性小、稳定性差、生物利用度低而在临床的应用受到限制的问题,将叶酸 -聚乙二醇 -脂质体(FA-PEG-Lip)、介孔碳纳米管(MCN)和 Res混合并超声处理,制备得到装载 Res的 FA-PEG-Lip包裹的 MCN(FA-PEG-Lip@MCN/Res)纳米体系。所获得的 FA-PEG-Lip@MCN/Res具有纳米级尺寸[宽:(80±10)nm;长:(600±100)nm]、负的表面电荷(-10.2 mV)、出色的载药量(131.59 mg/g MCN)、良好的溶液分散性和近红外(NIR)激光刺激 -响应释放能力等特点。由于叶酸受体介导的靶向运输, FA-PEG-Lip@MCN/Res纳米体系可以高特异性地将所运载的 Res转运到人乳腺癌细胞(MCF-7)。细胞增殖毒性试验表明,未装载药物的 FA-PEG-Lip@MCN其本身生物相容性良好,适于作为药物载体。一系列细胞水平及活体水平的肿瘤治疗试验证明,在 NIR激光照射下,该 FA-PEG-Lip@MCN/Res纳米体系表现出良好的化疗 /光热协同治疗作用,能够对肿瘤进行高效地杀伤。总而言之,该 FA-PEG-Lip@MCN/Res纳米体系能够同时实现提高 Res的水溶性、增强 Res的稳定性、延长 Res在小鼠体内的半衰期、叶酸受体靶向、 NIR激光刺激 -响应释放以及肿瘤协同治疗等诸多功能,有望进一步推动 Res在临床的应用。
Abstract
Resveratrol (Res) is a promising molecule for.ghting cancer. However, the potential of the drug is immensely hindered by several limiting factors, including poor water solubility, limited chemical stability, and low bioavailability. In or-der to solve the above problems, we report a facile synthesis of a Res-loaded folate-terminated PEG-liposome (FA-PEG-Lip) coated mesoporous carbon nanotube (MCN) nanosystem (FA-PEG-Lip@MCN/Res) by simply sonicating Res and MCN in FA-PEG-Lip suspensions. The as-obtained FA-PEG-Lip@MCN/Res exhibits a nanoscale size [width: (80±10) nm, length: (600±100) nm], a negative surface potential (-10.2 mV), an excellent drug loading (131.59 mg/g MCN), good monodisper-sity and near infrared (NIR) laser stimulation-response release. Owing to folate receptor-mediated targeted delivery, the FA-PEG-Lip@MCN/Res nanosystem can deliver loaded Res to human breast cancer MCF-7 cells with high speci.city. The cell toxicity viability shows that unloaded FA-PEG-Lip@MCN has no cytotoxicity, confirming its suitability as a drug vehicle. In addition, a systematic in vitro and in vivo experiments demonstrated that, under NIR laser irradiation, the FA-PEG-Lip@ MCN/Res nanosystem exhibits highly e.cient chemotherapy/photothermal synergistic therapy. All in all, the FA-PEG-Lip@ MCN/Res nanosystem can simultaneously improve Res water solubility, enhance Res stability, extend plasma half-life of Res in mice, folate receptor targeting, NIR laser stimulation-response release, and synergistic tumor therapy, which may greatly promote the application of Res in clinical practice.
参考文献

[1] MANZANO M, VALLET-REGí M. Mesoporous silica nanopar-ticles for drug delivery[J]. Advanced Functional Materials, 2020,30(2): 1902634.

[2] LU D, TAO R, WANG Z. Carbon-based materials for photody-namic therapy: a mini-review[J]. Frontiers of Chemical Science and Engineering, 2019, 13(2): 310-323.

[3] MENG Y, WANG S S, LI C Y, et al. Photothermal combined gene therapy achieved by polyethyleneimine-grafted oxidized mesopo-rous carbon nanospheres[J]. Biomaterials, 2016, 100: 134-142.

[4] CHEN L, ZHANG H, ZHENG J, et al. Thermo-sensitively and magnetically ordered mesoporous carbon nanospheres for targeted controlled drug release and hyperthermia application[J]. Materi-als Science & Engineering C, 2018, 84(1): 21-31.

[5] CAI X L, YAN H Y, LUOYN, et al. Mesoporous carbon nano-spheres with ZnO nanolids for multimodal therapy of lung cancer[J]. ACS Applied Materials & Interfaces, 2018, 1(4): 1165-1173.

[6] 庄煜,黄辉君,全媚媚,等.白藜芦醇的生物活性及作用机制[J].激光生物学报, 2019, 28(3): 212-218. ZHUANG Yu, HUANG Huijun, QUAN Meimei, et al. Biological properties and its mechanism of resveratrol[J]. Acta Laser Biol-ogy Sinica, 2019, 28(3): 212-218.

[7] KULASHEKAR M, STOM S M, PEULER J D. Resveratrol’potential in the adjunctive management of cardiovascular disease,sobesity, diabetes, Alzheimer disease, and cancer[J]. Journal of the American Osteopathic Association, 2018, 118(9): 596-605.

[8] JADHAV P, BOTHIRAJA C, PAWAR A. Resveratrol-piperine loaded mixed micelles: formulation, characterization, bioavail-ability, safety and in vitro anticancer activity[J]. RSC Advances, 2016, 6(114): 112795-112805.

[9] ATHAR M, BACK J H, TANG X W, et al. Resveratrol: a review of preclinical studies for human cancer prevention[J]. Toxicology and Applied Pharmacology, 2007, 224(3): 274-283.

[10] AMRI A, CHAUMEIL J C, SFAR S, et al. Administration of res-veratrol: what formulation solutions to bioavailability limitations[J]. Journal of Controlled Release, 2012, 158(2): 182-193.

[11] VARONA S, MARTíN á, COCERO M J. Liposomal incorporation of lavandin essential oil by a thin-film hydration method and by particles from gas-saturated solutions[J]. Industrial & Engineer-ing Chemistry Research, 2011, 50(4): 2088-2097.

[12] ZHAO Q F, LIN Y Z, HAN N, et al. Mesoporous carbon nano-materials in drug delivery and biomedical application[J]. Drug Delivery, 2017, 24(2): 94-107.

[13] MANTSO T, VASILEIADIS S, ANESTOPOULOS I, et al. Hyper-thermia induces therapeutic e.ectiveness and potentiates adjuvant therapy with non-targeted and targeted drugs in an in vitro model of human malignant melanoma[J]. Scienti.c Reports, 2018, 8(1): 10724.

[14] HAI L,HEDG,HEXX, et al. Facile fabrication of a resveratrol loaded phospholipid@reduced graphene oxide nanoassembly for targeted and near-infrared laser-triggered chemo/photothermal synergistic therapy of cancer in vivo[J]. Journal of Materials Chemistry B, 2017, 5(29): 5783-5792.

[15] 曹毛毛,陈万青.中国恶性肿瘤流行情况及防控现状[J].中国肿瘤临床, 2019, 46(3): 145-149. CAO Maomao, CHEN Wanqing. Epidemiology of cancer in China and the current status of prevention and control[J]. Chinese Jour-nal of Clinical Oncology, 2019, 46(3): 145-149.

[16] 郑荣寿,孙可欣,张思维,等. 2015年中国恶性肿瘤流行情况分析[J].中华肿瘤杂志, 2019, 41(1): 19-28. ZHENG Rongshou, SUN Kexin, ZHANG Siwei, et al. Report of cancer epidemiology in China, 2015[J]. Chinese Journal of On-cology, 2019, 41(1): 19-28.

[17] LIU H J, LI CW, QIANY, et al. Magnetic-induced graphene quantum dots for imaging-guided photothermal therapy in the sec-ond near-infrared window[J]. Biomaterials, 2020, 232: 119700.

[18] HUAX W, BAO YW, ZENG J, et al. Ultrasmall all-in-one nanodots formed via carbon dot-mediated and albumin-based syn-thesis: multimodal imaging-guided and mild laser-enhanced cancer therapy[J]. ACS Applied Materials & Interfaces, 2018, 10(49): 42077-42087.

[19] ZHANG B M, WANG Y, LIU J Y, et al. Recent developments of phototherapy based on graphene family nanomaterials[J]. Current Medicinal Chemistry, 2017, 24(3): 268-291.

[20] XU G J, LIU S J, NIU H, et al. Functionalized mesoporous carbon nanoparticles for targeted chemo-photothermal therapy of cancer cells under near-infrared irradiation[J]. RSC Advances, 2014,4(64): 33986-33997.

[21] ZHANG Y, CHANG Y Q, HAN L, et al. Aptamer-anchored di-polymer shell-capped mesoporous carbon as a drug carrier for bi-trigger targeted drug delivery[J]. Journal of Materials Chemistry B, 2017, 5(33): 6882-6889.

李璟, 伍旭, 彭倩, 王晨旭, 杨凡. 基于装载白藜芦醇的脂质体包裹介孔碳纳米管用于靶向及近红外激光触发的化疗 /光热协同肿瘤治疗[J]. 激光生物学报, 2020, 29(6): 550. LI Jing, WU Xu, PENG Qian, WANG Chenxu, YANG Fan. Liposome Coated Mesoporous Carbon Nanotube with Resveratrol Loading for Targeted and Near-infrared Laser-triggered Chemo/Photothermal Synergistic Cancer Therapy[J]. Acta Laser Biology Sinica, 2020, 29(6): 550.

关于本站 Cookie 的使用提示

中国光学期刊网使用基于 cookie 的技术来更好地为您提供各项服务,点击此处了解我们的隐私策略。 如您需继续使用本网站,请您授权我们使用本地 cookie 来保存部分信息。
全站搜索
您最值得信赖的光电行业旗舰网络服务平台!