负载天然环肽RA-V激活型产氧纳米颗粒用于乏氧肿瘤高效治疗的研究

The efficacy of cancer chemotherapy is seriously limited due to hypoxia, which has become an urgent problem that need to be solved in the field of drug research and development. Recently, we have developed two kinds of oxygen and drug dual-released nanocarriers to improve the therapeutic effect in hypoxic tumor. However, the application of these nanocarriers was restricted to traditional chemotherapy agents. Natural cyclopeptide RA-V, which was isolated from Rubia yunnanensis, was a kind of potential anti-tumor lead compound. A lot of researches have showed that RA-V had a potential anti-tumor activity in vitro and in vivo, but there are still several limitations in solubility and toxicity for new drug research and development of RA-V. To address these problems, some preliminary works have been carried out and showed that RA-V could be efficiently loaded on nanocarriers and selectively delivered to cancer tissues in vivo. On the basis of these works, this project plans to develop oxygen-evolving, RA-V-loading and RA-V/Doxorubicin-loading theranostic nano-systems: We will prepare nanoparticles that have a selective respond to hypoxia or reactive oxygen species. The generation of oxygen and release of drug in the nanoparticles occur at the same time. In addition, aptamers will be loaded on the surface of nanoparticles to realize the tumor targeting on subcellular level, achieving intracellular drug release in a spatiotemporally controlled manner. This project aims to construct a novel theranostic system with the targeted delivery of active natural cyclopeptide RA-V, dynamic tracking, and hypoxic microenvironment regulating function, which will provide new method for more precise and effective chemotherapy in hypoxic tumor tissue achieved by smart RA-V nanocarriers.

乏氧严重制约癌症化疗效果，是药物研究亟待解决的问题。前期发展了两种氧气与药物双重可控释放纳米载药体系，显著提高对乏氧肿瘤疗效，但在药物选择方面仍局限于传统化疗药物。从茜草科植物中分离得到的天然环肽RA-V是一种极具潜力的抗肿瘤先导化合物，对乳腺癌等多种癌症有很好体内外活性，但其新药研发受水溶性和毒性限制。针对此问题前期已初步证实RA-V可高效负载到纳米载体，并被靶向输送到肿瘤细胞内。因此本项目拟发展负载RA-V激活型产氧纳米诊疗体系：合成乏氧或活性氧特异性响应纳米载体，将氧气产生与药物释放有机结合，利用核酸适体表面功能化赋予纳米颗粒肿瘤细胞器靶向识别功能，协同经典化疗药物阿霉素，实现药物在细胞中定点程序释放，建立一种集天然环肽RA-V靶向输送、动态示踪、调控肿瘤乏氧微环境等功能于一体的智能纳米诊疗体系，为乏氧肿瘤的高效、精准治疗提供新思路和新方法。

乏氧严重制约癌症化疗效果，是药物研究亟待解决的问题。前期发展了两种氧气与药物双重可控释放纳米载药体系，显著提高对乏氧肿瘤疗效，但在药物选择方面仍局限于传统化疗药物。从茜草科植物中分离得到的天然环肽RA-V是一类极具潜力的抗肿瘤先导化合物，研究表明RA-V对乳腺癌等多种癌症有很好体内外活性，但其新药研发受水溶性和毒性限制。针对此问题前期已初步证实RA-V可高效负载到纳米载体，并靶向输送到肿瘤细胞内。因此本项目拟发展负载RA-V激活型产氧纳米诊疗体系：合成乏氧或活性氧特异性响应纳米载体，将氧气产生与药物释放有机结合，利用核酸适体表面功能化赋予纳米颗粒肿瘤细胞器靶向识别功能，协同经典化疗药物阿霉素，实现药物在细胞中定点程序释放，建立一种集天然环肽RA-V靶向输送、动态示踪、调控肿瘤乏氧微环境等功能于一体新型纳米诊疗体系，为负载环肽RA-V的智能纳米载体用于乏氧肿瘤的高效、精准治疗奠定基础。