微创介入法实现圆筒支架状紫杉醇植入剂靶向食道肿瘤长期缓释药物及其高效低毒抗肿瘤的研究

定位定向肿瘤长时间缓释化疗药物，可提高肿瘤组织的药物分布和蓄积，但其相应的抗肿瘤功效及机制尚未得到充分验证和阐明。腔道（如食道）肿瘤具有特殊的生理解剖特点，将载药支架状植入物植入到相应的腔道(食管)内可实现向腔道肿瘤长时间定位定向给药。本项目首先考察各种剂量紫杉醇长时间作用于兔VX2鳞癌细胞、人食管鳞癌或腺癌细胞，对其增殖、凋亡、细胞周期、耐药性、侵袭和转移性的影响；构建VX2食管癌恶性食管狭窄兔模型，研究圆筒支架状紫杉醇植入剂向肿瘤长时间大剂量缓释药物的抗肿瘤效应和安全性及其机制。揭示植入剂的剂量、释药行为、药物体内分布与动力学，尤其是药物在肿瘤内及其邻近组织的分布，与肿瘤生长、侵袭和迁移、肿瘤免疫微环境之间的关联性。阐明植入剂高效低毒抗肿瘤的机制和原因，为肿瘤（尤其是腔道肿瘤）化疗提供高效低毒的新治疗模式和科学依据。

Tumor specific and oriented extended release of chemotherapeutic agents ,which can effctively improve distribution and accumulation of chemotherapeutic agents in tummor, however, its antitumor effects and the underneath mechanism have not been fully verified and uncovered. Long-term esophagus tumor site-specific and oriented release of chemotherapeutic agents can be acquired by implanting one drug loaded stent like implant into the corresponding esophagus site due to physiological and anatomical characteristics of tract tumor (e.g. esophagus cancer). In this program, we firstly investigate that the effect of long-time co-cultivation of 3 kinds of tumor cells with paclitaxel on cell proliferation, apoptosis, multi-drug resistance, invasion and migration; then build VX2 tumor bearding rabbit with malignant esophagus stricture and study biosafety and efficacy of a cylindric stent implant containing paclitaxel which is closely adjacent to or contact tumor massively by virtue of transoral implanting it in the malignantly strictured part of esophagus of VX-2 tumor bearing rabbit. The research achievements will clarify the correlation among drug loadings, drug release profiles, and drug biodistribution and pharmacokinetics (especilally drug distribution of tumor and its adjacent tissue), as well as tumor growth, invasion, migration, metastasis and tumor immune microenvironment, uncovering the possible mechanism and reasons of the high-efficacy and low-toxicity antitumor effects. It will provide a scientific basis and a new high-efficacy and low-toxicity cancer treatment modality for tumor (especially tract tumor) chemotherapy.