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间充质干细胞的肿瘤归巢特性及其肿瘤靶向治疗应用研究进展
引用本文:李艾,张添源,高建青. 间充质干细胞的肿瘤归巢特性及其肿瘤靶向治疗应用研究进展[J]. 浙江大学学报(医学版), 2020, 49(1): 20-34. DOI: 10.3785/j.issn.1008-9292.2020.02.22
作者姓名:李艾  张添源  高建青
作者单位:1. 浙江大学药学院药物制剂研究所, 浙江 杭州 3100582. 浙江大学药学院浙江省抗肿瘤药物临床前研究重点实验室, 浙江 杭州 310058
基金项目:国家自然科学基金(81620108028, 81703423)
摘    要:间充质干细胞(MSC)具有受肿瘤组织或肿瘤微环境释放的多种趋化因子吸引而向肿瘤组织靶向归巢的天然属性,因此有望成为一种新型的活细胞传递载体用于抗肿瘤药物/基因的靶向递送。外源性MSC静脉注射后会首先在肺部被大量截留,经肺清除后向肿瘤组织归巢,可以通过增强趋化因子与MSC上受体的相互作用或改变注射方式减少MSC截留等方法改善MSC的肿瘤归巢效率。基于MSC的传递系统可用于靶向递送阿霉素、紫杉醇和吉西他滨等化疗药物,帮助解决化疗药物半衰期较短、肿瘤靶向性较差等问题。其次,MSC可以通过基因重组的方式有效保护和靶向递送肿瘤细胞杀伤基因、免疫系统调节基因等治疗基因,通过在肿瘤部位特异性表达治疗基因实现肿瘤抑制或杀伤作用。此外,MSC还可以作为细胞传递载体靶向递送诊疗药物,发挥肿瘤诊疗一体化的治疗作用。总之,基于MSC的细胞载体递送系统可实现化疗药物、治疗基因和诊疗药物的靶向递送并在多种类型的肿瘤靶向治疗中取得良好的疗效。相信随着这一细胞载体递送策略的不断改良和优化,基于MSC的靶向传递系统将为肿瘤靶向治疗提供一种新的传递策略和治疗选择。

关 键 词:药物递送系统  药物载体  基因靶向  肿瘤  间充质干细胞  综述  
收稿时间:2019-11-20

Progress on utilizing mesenchymal stem cells as cellular delivery system for targeting delivery of as drug/gene for anti-tumor therapy
LI Ai,ZHANG Tianyuan,GAO Jianqing. Progress on utilizing mesenchymal stem cells as cellular delivery system for targeting delivery of as drug/gene for anti-tumor therapy[J]. Journal of Zhejiang University. Medical sciences, 2020, 49(1): 20-34. DOI: 10.3785/j.issn.1008-9292.2020.02.22
Authors:LI Ai  ZHANG Tianyuan  GAO Jianqing
Affiliation:1. Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China2. Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
Abstract:Mesenchymal stem cells (MSCs) have the inherent tumor-homing ability with the attraction of multiple chemokines released by tumor tissues or tumor microenvironments, which can be utilized as promising cellular carriers for targeted delivery of anti-tumor drugs and genes. In most circumstances, large amount of systemicly administrated MSCs will be firstly trapped by lungs, following with re-distribution and homing to tumor tissues after lung clearance. Several approaches like enhanced interactions between chemokines and receptors on MSCs or reducing the retention of MSCs by changes of administration methods are firstly reviewed for improving the homing of MSCs towards tumor tissues. Additionally, the potentials and gains of utilizing MSCs to carry several chemotherapeutics, such as doxorubicin, paclitaxel and gemcitabine are summarized, showing the advantages of overcoming the short half-life and poor tumor targeting of these chemotherapeutics. Moreover, the applications of MSCs to protect and deliver therapeutic genes to tumor sites for selectively tumor cells eliminating or promoting immune system are highlighted. In addition, the potentials of using MSCs for tumor-targeting delivery of diagnostic and therapeutic agents are addressed. We believed that the continuous improvement and optimization of this stem cells-based cellular delivery system will provide a novel delivery strategy and option for tumor treatment.
Keywords:Drug delivery systems  Drug carriers  Gene targeting  Neoplasms  Mesenchymal stem cells  Review  
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