【作者】 牟全兵； 马媛； 朱新远； 颜德岳；

【Author】 Quanbing Mou;Yuan Ma;Xinyuan Zhu;Deyue Yan;School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University;

【机构】 上海交通大学化学化工学院金属基复合材料国家重点实验室；

【摘要】 纳米技术是癌症治疗中药物输送的重要输送手段之一。但传统的纳米输送系统往往因其载体的使用,造成批次之间的差异性和毒副作用,极大限制了该输送系统的临床应用。^[1]为了解决这些问题,我们发展了一种新型的智能响应型纳米给药系统,该系统直接将亲水性的小分子靶向剂乳糖酸和疏水性的抗肿瘤药物阿霉素缀合。因缀合物的两亲性,缀合物可在水中自组装形成纳米粒子。由于肿瘤部位增强的渗透和滞留（EPR）效应以及小分子靶向剂的主动靶向作用,该体系具有双重靶向的特性。通过p H敏感的酰腙键缀合,赋予了该体系在肿瘤组织和肿瘤细胞中智能响应的特点。体外细胞实验和体内动物实验证明该纳米药物输送体系具有和原药相当的抗肿瘤活性,但缀合物纳米药的毒副作用更小。同时,该体系的阿霉素载药率高达61.7%,可实现抗肿瘤药物的高效负载。这种简单的纳米药物构筑方法会为抗肿瘤药物的输送提供新的思路,同时因缀合物具有明确的结构,该体系还具有潜在的临床应用价值。更多还原

【Abstract】 Targeted drug delivery is a broadly applicable approach for cancer therapy. However, the nanocarrier-based targeted delivery system suffers from batch-to-batch variation, quality concerns and carrier-related toxicity issues. Thus, to develop a carrier-free targeted delivery system with nanoscale characteristics is very attractive. Here, a novel targeting small molecule nanodrug self-delivery system consisting of targeting ligand and chemotherapy drug was constructed, which combined the advantages of small molecules and nano-assemblies together and showed excellent targeting ability and long blood circulation time with well-defined structure, high drug loading ratio and on-demand drug release behavior. As a proof-of-concept, lactose(Lac) and doxorubicin(DOX) were chosen as the targeting ligand and chemotherapy drug, respectively. Lac and DOX were conjugated through a pH-responsive hydrazone group. For its intrinsic amphiphilic property, Lac-DOX conjugate could self-assemble into nanoparticles in water. Both in vitro and in vivo assays indicated that Lac-DOX nanoparticles exhibited enhanced anticancer activity and weak side effects. This novel active targeting nanodrug delivery system shows great potential in cancer therapy.更多还原