肿瘤特异靶向的长循环多功能纳米胶束用于肝癌的光声成像及光热/光动力协同治疗研究

本课题针对肿瘤微酸环境与肝癌表面的特异分子标志物，设计一种具有肝癌特异靶向能力的长循环、多功能纳米胶束，用以实现对肝癌的光声成像和光热/光动力协同治疗。在生理条件下，胶束表面的两性离子使纳米胶束呈电中性，可使其避免被网状内皮系统清除，延长血液循环时间，有利于通过高通透与滞留效应（EPR）提高药物在肿瘤部位的富集度。在肿瘤间质微酸环境中，胶束表面的两性电荷翻转为正电荷，易于被癌细胞摄取；同时，胶束表面的特异性靶向配体可进一步增加肝癌细胞对纳米胶束的选择性摄取。胶束内部包裹二氢卟吩e6（Ce6）和半导体聚合物量子点（Pdots）。半导体聚合物量子点具备光声造影和光热转换的功能，因此该纳米胶束可用于肝癌的光声成像和光热治疗；同时，半导体聚合物量子点产生的过高热，能够使纳米胶束达到玻璃化温度而产生相变熔化，进而释放出Ce6分子并激活Ce6分子的光敏化活性，实现对肝癌的光热/光动力协同治疗。

Here, we intend to design a long circulation, multifunctional hepatocellular carcinoma (HCC) targeting nanomicelles, which are based on the slightly acidic environment of the tumor tissues and the specific surface biomarkers, for the targeting photoacoustic imaging and photothermal/photodynamic synergistic therapy of HCC. Under physiological conditions, the nanomicelle’s surface which possesses approximately equal positive and negative charges can protect them from being eliminated by the reticuloendothelial system, then prolong the blood circulation and further improve the tumor tissue targeting by passive accumulation via the enhanced permeability and retention (EPR) effect. Due to the slightly acidic feature of the tumor extracellular environment, the zwitterionic charges on the nanomicelle’s surface can switch to positive which can significantly enhance the cellular uptake due to the strengthened nanomicelle-cellular membrane interaction; furthermore, the specific targeting ligand on the micelle’s surface would further increase the specific uptake by hepatocellular carcinoma cancer cells via the ligand-receptor interactions. The photo sensitizer Ce6 and semiconducting polymer nanoparticles (Pdots) were packed inside the nanomicelles; since the Pdots have excellent photoacoustic contrast ability and photo-thermal conversion ability, the nanomicelles could be applied for the targeting photoacoustic imaging and photothermal therapy of HCC. Meanwhile, the encapsulated photo sensitizer Ce6 could be released and activated by destroying the nanomicelles via the high temperature that produced by the Pdots under infra-red laser irradiation, then it would further facilitate the photothermal/photodynamic synergistic therapy of HCC. This project would provide further valuable information for design novel HCC targeting theranostic agents.