心肌梗死是由冠状动脉阻塞所引起的心肌缺氧坏死,其发病率和病死率居高不下。近年研究发现,利用组织工程手段仿生构建心肌微环境能有效改善心肌梗死区微环境,对心肌的再生能力有着重要的调控作用,能在一定程度上促进心肌再生,有望成为将来治疗心肌梗死的新方向。然而,由于对仿生心肌微环境和机体微环境交互作用、引发的生物学效应及作用机制不清楚,直接影响心肌损伤修复的过程和质量。因此,阐明仿生心肌微环境在心肌损伤修复过程中的交互作用过程及其介导的生物学效应迫在眉睫。该文系统性综述了仿生心肌微环境的构建策略及植入体内后介导的生物学效应,包括免疫调控效应、促血管再生效应以及再生协同效应等,为新型心肌补片的仿生设计和临床应用提供理论支持。
Myocardial infarction（MI）,arising from coronary artery obstruction resulting in hypoxic necrosis of myocardium,remains high morbidity and mortality．Recent studies have revealed that constructing myocardial microenvironment bionically through tissue engineering methods can effectively ameliorate the microenvironment in the infarcted area and exert a crucial regulatory role in myocardial regeneration,which promotes myocardial regeneration to a certain extent and holds promise for the treatment of MI．However,the interaction between biomimetic myocardial microenvironment and host microenvironment,as well as the triggered biological effects and mechanisms are not clear,which directly affects the process and quality of myocardial repair．Therefore,it is urgent to clarify the interaction process and biological effects mediated by the biomimetic myocardial microenvironment during myocardial repair．This review systematically summarizes the construction strategies of biomimetic myocardial microenvironment and their mediated biological effects after implantation,including immunomodulatory effects,pro-vascular regenerative effects,and regenerative synergistic effects,which provides theoretical support for the biomimetic design and clinical application of novel cardiac patches．
实体肿瘤物理和化学微环境异常阻碍了肿瘤与外界进行物质交换,降低了药物渗入肿瘤组织,是肿瘤对放化疗抵抗的重要原因。目前,已有多种针对肿瘤微环境各个组分的治疗方法,如使血管正常化、降低肿瘤间质液压、降解细胞外基质等,以达到增强药物等的渗出,从而增强肿瘤治疗效果。声学调控是改变肿瘤理化微环境的一种有效方法,本文对声学调控其中几个主要的机制和研究进展进行综述,以期为临床肿瘤治疗提供新思路。
与正常组织细胞微环境相比,肿瘤微环境具有一定的异质性,包括偏酸性、氧化还原状态失衡、存在高浓度活性氧以及酶过量表达等。根据以上肿瘤微环境特点,可设计出一系列通过各种特殊微环境响应型连接臂相连的小分子或聚合物前药纳米粒。其中,多柔比星阿霉素作为一类最常见的广谱抗肿瘤药物在治疗肿瘤的过程中发挥重要作用。文章探讨了在肿瘤微环境特异性的生理状态下针对不同微环境所设计的多柔比星前药及其释放特性等,归纳总结了肿瘤微环境响应型多柔比星前药的研究进展。
Compared with normal tissue cell microenvironment, there is some differences in tumor microenvironment, such as partial acidity, imbalance of redox state, high concentration of reactive oxygen species and cathepsin. According to the above characteristics of tumor microenvironment, a series of small molecule or polymer prodrug nanoparticles connected by various special microenvironment responsive structures can be designed. Doxorubicin, as one of the most common broad-spectrum antitumor drugs, plays an important role in the treatment of tumors. This review discusses the doxorubicin prodrug designed for different tumor microenvironments under the physiological state of tumor microenvironment specificity and their release characteristics, and summarizes the research progress of tumor microenvironment-responsive doxorubicin prodrug.
