納米藥物用于惡性腫瘤治療時最棘手的問題之一是腫瘤靶向效率較低，釋放的藥物難以特異性殺死腫瘤細胞,。腫瘤靶向效率已成為納米藥物研發(fā)和臨床應(yīng)用的瓶頸問題,。
針對納米材料腫瘤靶向性差這一問題，中科院理化技術(shù)研究所納米材料可控制備與應(yīng)用研究室在唐芳瓊研究員的帶領(lǐng)下,，近年來一直致力于發(fā)展新型納米載體及其生物醫(yī)學(xué)應(yīng)用,。2009年他們發(fā)表了合成具有中空介孔結(jié)構(gòu)的夾心二氧化硅的新方法（Adv. Mater. 2009, 21, 3804-3807）,，之后在夾心二氧化硅的生物醫(yī)學(xué)應(yīng)用方面做了一系列工作，相關(guān)文章發(fā)表在Angew Chem. Int. Ed.,、ACS Nano,、Biomaterials上。
近日,，他們聯(lián)合首都醫(yī)科大學(xué)宣武醫(yī)院,、深圳市孫逸仙心血管醫(yī)院、軍事醫(yī)學(xué)科學(xué)院,、北京華美精創(chuàng)納米相材料科技有限責(zé)任公司等多家單位,，設(shè)計了一種全新高效的腫瘤靶向策略：將載藥夾心二氧化硅納米顆粒結(jié)合到間充質(zhì)干細胞上，間充質(zhì)干細胞受到腫瘤細胞分泌的細胞因子的吸引可以主動追蹤到腫瘤細胞,，將載藥納米顆粒輸送到腫瘤組織的各個部位,，釋放藥物導(dǎo)致腫瘤細胞凋亡。這一全新的靶向方法采用具有趨化作用的間充質(zhì)干細胞作為“靶向運輸車”,，像“特洛伊木馬”一樣,，里應(yīng)外合徹底殺死腫瘤細胞，相比傳統(tǒng)的靶向方法具有更強的主動性,、目標(biāo)性和靶向性,。
該研究成果為納米藥物的腫瘤靶向方法開拓了新的思路，并為改善納米藥物臨床應(yīng)用帶來了新的希望,。審稿人認為,，“他們采用了創(chuàng)新和有趣的納米材料，和間充質(zhì)干細胞結(jié)合,，使載藥納米顆粒像子彈一樣高效靶向,、殺死腫瘤細胞”。
研究成果近期在《ACS納米》（ACS Nano）上在線發(fā)表,。該研究獲得國家科技部“863”項目和國家自然科學(xué)基金項目的大力支持,。(生物谷 Bioon.com)
doi:10.1021/nn202399w
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Silica Nanorattle–Doxorubicin-Anchored Mesenchymal Stem Cells for Tumor-Tropic Therapy
Linlin Li,Yunqian Guan,Huiyu Liu,Nanjing Hao,Tianlong Liu,Xianwei Meng,Changhui Fu,Yanzhen Li,Qiulian Qu,Yingge Zhang,Shangyi Ji,Ling Chen,Dong Chen,Fangqiong Tang,
Low targeting efficiency is one of the biggest limitations for nanoparticulate drug delivery system-based cancer therapy. In this study, an efficient approach for tumor-targeted drug delivery was developed with mesenchymal stem cells as the targeting vehicle and a silica nanorattle as the drug carrier. A silica nanorattle–doxorubicin drug delivery system was efficiently anchored to mesenchymal stem cells (MSCs) by specific antibody–antigen recognitions at the cytomembrane interface without any cell preconditioning. Up to 1500 nanoparticles were uploaded to each MSC cell with high cell viability and tumor-tropic ability. The intracellular retention time of the silica nanorattle was no less than 48 h, which is sufficient for cell-directed tumor-tropic delivery. In vivo experiments proved that the burdened MSCs can track down the U251 glioma tumor cells more efficiently and deliver doxorubicin with wider distribution and longer retention lifetime in tumor tissues compared with free DOX and silica nanorattle-encapsulated DOX. The increased and prolonged DOX intratumoral distribution further contributed to significantly enhanced tumor-cell apoptosis. This strategy has potential to be developed as a robust and generalizable method for targeted tumor therapy with high efficiency and low systematic toxicity
