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本文探索以生物素为导向分子介导纳米载体靶向胰腺癌并开展光动力治疗的可行性。以聚乙二醇-磷脂酰乙醇胺[poly(ethylene glycol)-distearoyl phosphatidyl ethanolamine,m PEG2000-DSPE]为载体材料,生物素-聚乙二醇-磷脂酰乙醇胺[biotin-poly(ethylene glycol)-distearoyl phosphatidyl ethanolamine,Biotin-PEG3400-DSPE]为功能材料,通过薄膜水化法制备生物素修饰的聚合物胶束。通过体外细胞摄取实验和体内荧光活体成像实验考察其靶向性并对导向分子的比例进行优选。在此基础上,以新型光动力药物竹红菌乙素为光敏剂,制备载药胶束制剂并对其体内外药效进行系统评价。结果表明,5%(mol/mol)比例的生物素修饰具有相对较好的体内外靶向性,其载药制剂粒径较小[(36.74±2.16)nm]且分布较均一,药物的包封率较高,达到(80.06±0.19)%。药效评价显示,经生物素介导能提高光敏剂对Bx PC-3细胞的光毒性,在体内则表现为显著抑制裸鼠皮下瘤生长。本研究成功地将生物素介导主动靶向的“抑瘤谱”扩大至胰腺癌,所得载光敏剂胶束的制剂学性质较好,为胰腺癌尤其是部分难渗透、放化疗不敏感的胰腺癌治疗研究提供了有益的思路。
This article explored the biotin-oriented molecular-mediated nanocarriers targeting pancreatic cancer and the feasibility of photodynamic therapy. Poly (ethylene glycol) -distearoyl phosphatidyl ethanolamine (m PEG2000-DSPE) was used as a carrier material, biotin-poly (ethylene glycol) -distearoyl phosphatidyl ethanolamine, Biotin-PEG3400-DSPE] as functional materials, biotin-modified polymer micelles were prepared by membrane hydration method. Through the in vitro cell uptake experiments and in vivo fluorescence in vivo imaging experiments to investigate its targeting and targeting the proportion of molecules preferred. On this basis, a new photodynamic drug, hypocrellin B, was used as a photosensitizer to prepare drug-loaded micellar formulations and evaluate their in vivo and in vitro pharmacodynamics. The results showed that the 5% (mol / mol) biotinylated biotin had relatively good targeting in vitro and in vivo, and its particle size was smaller ([36.74 ± 2.16] nm] Sealing rate is higher, reaching (80.06 ± 0.19)%. Efficacy evaluation showed that the biotin-mediated photosensitizer can improve the phototoxicity of Bx PC-3 cells in vivo showed significant inhibition of nude mice growth of subcutaneous tumor. In this study, we successfully expanded the biotin-mediated active targeting anti-tumor spectrum to pancreatic cancer. The obtained photosensitizer micelles showed good preparation properties, especially for pancreatic cancer, especially partially refractory to radiotherapy and chemotherapy Sensitive pancreatic cancer treatment research provides a useful idea.