酶响应性纳米粒子治疗肿瘤:纳米粒子积累和药物释放的优势

Enzyme-responsive nanoparticles in tumor therapy:superiority of nanoparticles in accumulation and drug release

背景:基于纳米药物递送系统在肿瘤中增强的渗漏与滞留效应,以设计对刺激产生响应的抗肿瘤药物递送载体是最近肿瘤治疗策略发展的一大方向。酶响应性纳米递送系统是其中重要的组成部分,以肿瘤特异性高表达的酶作为精准靶向目标,大幅提高靶向性能。目的:总结近年来肿瘤治疗研究中酶响应性纳米粒子的设计思路、靶向效率及抗肿瘤效果。方法:检索PubMed、Web of Science、CNKI数据库、万方数据库等收录的与肿瘤治疗相关的酶响应性纳米粒子文章,英文检索词为"nanoparticles;neoplasms;enzymes;drug carriers;responsive",中文检索词为"纳米粒子;肿瘤;酶;药物载体;响应"。根据纳入与排除标准对所有文章进行初筛后,保留相关性较高的文章进行综述。结果与结论:目前的酶响应性纳米粒子可分为释药型和功能型2个基本类型,每种类型又进一步分为若干小类,不同的设计类型可以针对不同的肿瘤及其微环境特点。其中,释药型酶响应性纳米粒子主要专注于利用酶响应实现药物在肿瘤内的特定位点控释,功能型酶响应性纳米粒子则注重提高纳米粒子对肿瘤的靶向效率及在肿瘤中的积累,两者均因特异性的酶响应而实现药物在肿瘤内的特异性释放,从而降低全身毒性,提高抗肿瘤效果。根据目前的研究趋势,未来酶响应性将作为多重响应性纳米粒子抗肿瘤药物设计的一部分逐渐发展,同时将会发现更多肿瘤特异性酶及响应机制,以应对复杂的肿瘤类型及其微环境。

BACKGROUND:Based on enhanced permeability and retention effect of nanoscale drug delivery systems in tumors,intelligent design of anti-tumor drug delivery vehicles has recently become a major direction in the development of tumor treatment strategies.Among them,the enzyme-responsive nanodelivery system has played a relatively important role,taking tumor-specific and highly expressed enzymes as precise targets so as to greatly improve targeting performance.OBJECTIVE:To summarize researches on the protocol,targeting efficiency and anti-tumor effects of enzyme-responsive nanoparticles in cancer treatment in recent years.METHODS:PubMed,Web of Science,CNKI and Wanfang databases were searched for the articles concerning the enzyme-responsive nanoparticles related to tumor treatment,with the search terms of"nanoparticles;neoplasms;enzymes;drug carriers;responsive"in English and Chinese,respectively.After initial screening of all articles according to inclusion and exclusion criteria,those with higher relevance were retained for the successive review.RESULTS AND CONCLUSION:Currently,enzyme-responsive nanoparticles are classified into two basic types in the article:drug-releasing type and functional type.Both are further divided into several sub-categories.Different designs target at corresponding tumors and their microenvironment characteristics.Among them,drug-releasing enzyme-responsive nanoparticles are designed to achieve controlled release of drugs at specific sites in tumors by enzyme response,while functional enzyme-responsive nanoparticles focus on improving the targeting efficiency and accumulation of nanoparticles in tumors.Both main types achieved specific release of drugs in tumors due to corresponding enzyme response,thereby reducing systemic toxicity and improving anti-tumor effects.According to current research trends,enzyme responsiveness is gradually turning into a part of the design of multiple responsive nanoparticle antitumor drugs in coming years.More tumor-specific enzymes and response mechanisms will be discovered to cope with complex tumor types and their microenvironment as well.