目前临床上还没有一种针对肺鳞癌的特效药。由于10%-20%的肺鳞癌患者存在FGFR1高表达, 故根据个体化治疗策略，本项目拟针对小分子抗肿瘤药物现有的临床缺陷和肺癌不同分子亚型之间的差异，设计构建一种具有多级肿瘤靶向的pH敏感聚合物-PEG-tbFGF纳米载体系统，同时装载紫杉醇和阿司匹林衍生物，将双药协同效应、长循环纳米粒的天然肿瘤靶向、pH敏感的物理化学靶向和tbFGF介导的主动靶向有机结合，实现对高表达FGFR的肺鳞癌组织的特异靶向作用和双药协同抗肿瘤作用。本项目旨在阐明该纳米载体主动靶向肿瘤和智能逐级释药的机制，以及两种化疗药物抗肿瘤信号通路间的对话机制，为提高药物对肺鳞癌的疗效，降低毒副作用提供新方法和新思路。本项目研究结果可为肺鳞癌治疗提供一种理想的靶向载体和联合用药方案，具有较高的研究价值。

Currently, there is no particularly effective drug for clinical treatment of lung squamous carcinoma. Because 10%-20% of patients of lung squamous cell carcinoma have high expression of FGFR1, according to individualized treatment strategies, based on the cognition of clinical dosage forms’ defects of existing small molecule anticancer drugs and gene expressing differences between different lung cancer classifications, this project is proposed to design and synthesize several functional polymer materials, and establish one type of intelligent tbFGF-mediated and pH responsive nano-sized drug delivery system, which encapsulates paclitaxel and aspirin derivative together and is able to exert specific targeting effect, as well as dual drug synergistic anti-tumor effect, to lung squamous carcinoma tissue with high FGFR expression level. We will study this drug delivery system’s physicochemical characteristics and anti-tumor effects from the perspectives of nano-sized carrier establishment, in vitro cellular evaluation, Zebrafish heart micro cavity transplant carcinoma model evaluation, and in vivo pharmacodynamics, pharmacokinetics and tissue distribution studies on tumor-burdened mice model. We also aim elucidate the molecular mechanisms of active targeting effects on tumor and intelligent stepwise drug release behavior, as well as the dialogue mechanism between the signaling pathways of two anti-tumor chemotherapy agents. The results of this project will provide new approaches and new ideas for improving the treatment efficacy of lung squamous cell carcinoma, and reduced the toxicity to patients. Therefore, this project is worthy of implementation.