纳米粒通过EPR效应可携带化疗药物，靶向肿瘤组织，在肿瘤靶向治疗中显示出极大优势。然而EPR效应受肿瘤血管化程度及血管孔径影响大，因此，仅依靠EPR效应难以实现对肿瘤的特异性靶向。采用肿瘤细胞特异性识别分子修饰纳米粒，可提高纳米粒的肿瘤靶向性。项目前期证实Bombesin不仅高亲和、高选择结合肿瘤细胞，还能携带杀伤分子选择性杀伤肿瘤细胞。后续研究发现Bombesin的修饰提高了肿瘤细胞对纳米粒的摄取，提示Bombesin可增强纳米粒的肿瘤靶向能力。本项目拟进一步采用Bombesin修饰纳米粒，确定其对肿瘤靶向性的增强作用及包载化疗药物的体内外抗肿瘤效果，评价将其开发为新型靶向递药纳米粒的可能性。项目选择的天然肿瘤导向肽Bombesin具有分子小、亲和力强等优点，采用Bombesin修饰纳米粒，可望推出系列自主产权、高选择性、无/低毒、水溶性的靶向递药纳米粒，为肿瘤靶向治疗提供新选择。

Nanoparticles can be used as carriers to take chemotherapy drugs targeting to tumors via the enhanced permeability and retention (EPR) effect, which displays great advantages in tumor-targeted therapy. However, the EPR effect largely depends on the degree of tumor vascularization and porosity of tumor vessels. Therefore, it is still difficult to achieve specific tumor targeting if only relying on EPR effect. Attachment of tumor targeting moieties to the nanoparticles could enhance their targeting ability. We have demonstrated that Bombesin can bind to tumor cells with high affinity and specificity. Besides, conjugation of Bombesin to toxin molecules can significantly enhance their cytotoxicity to tumor cells. Subsequently, we found that Bombesin could increase the celluar uptake of nanoparticles in tumor cells, which indicates that attachment of Bombesin to nanoparticles may enhance their targeting ability. In this project, we will test the hypothesis in detail that nanoparticles grafted with Bombesin could target the tumors and could further enhance the antitumor efficacy of chemotherapy drugs. Hence, this work will evaluate the possibly of targeted delivery of anticancer drugs by Bombesin-grafted nanoparticles. This natural tumor-homing peptide Bombesin has the advantage of small size and high affinity. By attachment of Bombesin to nanoparticles, it is expected to develop the highly specific, no/low toxic and water-soluble targeting carriers with independent intellectual property rights for efficient delivery of anticancer drugs to tumor cells.