紫杉醇
乳腺癌
药物输送
癌症研究
药品
化疗
材料科学
免疫检查点
转移性乳腺癌
免疫疗法
癌症干细胞
药理学
免疫系统
转移
癌症
纳米技术
医学
癌细胞
内科学
免疫学
作者
Tianqun Lang,Yiran Liu,Zhong Zheng,Ran Wei,Yihui Zhai,Yaping Li,Pengcheng Zhang,Haijun Yu
标识
DOI:10.1002/adma.201806202
摘要
Abstract Metastatic breast cancer may be resistant to chemo‐immunotherapy due to the existence of cancer stem cells (CSC). Also, the control of particle size and drug release of a drug carrier for multidrug combination is a key issue influencing the therapy effect. Here, a cocktail strategy is reported, in which chemotherapy against both bulk tumor cells and CSC and immune checkpoint blockade therapy are intergraded into one drug delivery system. The chemotherapeutic agent paclitaxel (PTX), the anti‐CSC agent thioridazine (THZ), and the PD‐1/PD‐L1 inhibitor HY19991 (HY) are all incorporated into an enzyme/pH dual‐sensitive nanoparticle with a micelle–liposome double‐layer structure. The particle size shrinks when the nanoparticle transfers from circulation to tumor tissues, favoring both pharmacokinetics and cellular uptake, meanwhile achieving sequential drug release where needed. This nano device, named PM@THL, increases the intratumoral drug concentrations in mice and exhibits significant anticancer efficacy, with tumor inhibiting rate of 93.45% and lung metastasis suppression rate of 97.64%. It also reduces the proportion of CSC and enhances the T cells infiltration in tumor tissues, and thus prolongs the survival of mice. The cocktail therapy based on the spatio‐temporally controlled nano device will be a promising strategy for treating breast cancer.
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