“化疗-光热协同治疗”纳米粒子在生物安全性及药物控释能力方面的不足一直限制其进一步提高乳腺癌治疗效果及进入临床应用的可能性。因此，本项目将利用肿瘤组织的弱酸性环境及光热治疗使肿瘤部位温度升高的特点，合成一种具有光热转化功能的UCST、pH双响应型纳米材料用于化疗-光热协同治疗，从而实现通过近红外激光及肿瘤微环境实时、精确控制药物释放。首先，合成聚（鸟氨酸-瓜氨酸）共聚物，并利用透明质酸、细菌叶绿素及组胺酸衍生物对其进行修饰，进而在具有良好生物安全性的前提下，不仅可通过瓜氨酸脲基形成的分子间氢键及组氨酸咪唑基团的酸敏感性而兼具UCST、pH双响应性，还可利用细菌叶绿素在近红外光谱区的光热转化能力而具有光热升温功能；同时，利用该聚合物制备的纳米载体包载可高效杀伤乳腺癌干细胞的化疗药物，通过化疗-光热协同治疗对乳腺癌细胞及乳腺癌干细胞进行杀伤，提高乳腺癌治疗效果，并为改善缓控释药技术提供新方法。

The problems of biosecurity and drug release still limit the chemo-photothermal nano-therapeutics to achieving a further enhanced therapeutic effect on breast cancer and applying in clinic. Based on the weakly acidic environment and the increased temperature in tumor after the photothermal therapy, the UCST - (upper critical solution temperature) and pH-sensitivity copolymer with the light-thermal conversion ability will be synthesized in this study, the controlled release of which can be driven by near-infrared light and tumor microenvironment. Firstly, the poly(ornithine-co-citrulline) copolymer will be synthesized, which will be subsequently modified with hyaluronic acid, bacteriochlorophyll and histidine derivative. On the premise of biosecurity, this copolymer not only possesses UCST- and pH-sensitivity due to the intermolecular hydrogen bond formed from the ureido of citrulline and the imidazole ring of histidine, but also has the light-thermal conversion ability because of the modification of the bacteriochlorophyll. Additionally, after the selective inhibition agent of breast cancer stem cell is encapsulated in the nanoparticles prepared by this copolymer, a novel chemo-photothermal nano-therapeutics will be established, which can simultaneously eliminate the breast cancer cells and the breast cancer stem cells via the chemo-photothermal therapy. Therefore, this study will provide a new strategy to enhance the therapeutic efficiency of the breast cancer and improve the capacity of the controlled drug release of the nano-drug delivery system.