结直肠癌死亡率高，严重危害人类健康。本项目利用病毒样颗粒（VLPs）与天然病毒结构的相似性、良好的可塑性、独特的承载分子的能力，构建新型药物递送载体用于结直肠肿瘤的治疗。首先将具有结直肠肿瘤及肿瘤新生血管多重靶向功能的配体（TK肽）通过基因工程技术修饰到细小病毒（PPV）结构蛋白VP2形成的病毒样颗粒表面，构建出纳米载体TK-VLPs，从而实现精准递送TK-VLPs进入靶细胞的目的。其可能通过受体介导的内吞途径入胞，采用不同的抑制剂，考察TK-VLPs的胞吞机制。进一步评价了TK-VLPs作为药物载体在体内的安全性、稳定性及体内的药动学行为。然后以阿霉素为模型药物，考察TK-VLPs载阿霉素后的体内外抗肿瘤效果，探索TK-VLPs作为药物载体的可行性，以期构建出一种毒副作用更小、更安全的新型纳米载体；该工作将为开发新型的纳米载体提供可靠的科学依据。

Colorectal cancer has a high mortality, which is serious harm to human health.This study intends to construct new-type drug carriers to treat colorectal tumor depending on the inherent advantages of virus-like particles (VLPs), such as similar structure with nature virus, good plasticity of structure and special capacity of molecules. TK peptide targeting colorectal tumor cells and tumor angiogenesis was obtained in previous study. Then the sequence of the TK peptide was genetically inserted into the surface loops of the VP2 capsid protein of PPV virus and expressed in insect cells to produce the TK-VLPs that could be accurately delivered to target cell. We hypothesize that TK-VLPs could get into a cell by receptor-mediated endocytosis. Different inhibitors were used to investigate endocytosis mechanism of TK-VLPs. Then we investigate safety and stability of TK-VLPs in vitro and in vivo and its pharmacokinetics behavior in vivo. Meanwhile, in order to form a new-type nanocarrier which is less side-effect and more safe, doxorubicine will be used as a model drug to investigate pharmacodynamics of TK-VLPs in vitro and in vivo whether TK-VLPs as drug carrier is feasible. This study will provide reliable and scientific evidence to develop new-type nanocarrier.