紫杉醇
癌症研究
癌症
肿瘤微环境
乳腺癌
免疫疗法
PLGA公司
癌细胞
药物输送
化学
癌症免疫疗法
药理学
医学
体外
内科学
生物化学
有机化学
作者
Kavya Sree Maravajjala,K. Laxmi Swetha,Aniruddha Roy
标识
DOI:10.1016/j.xphs.2022.05.008
摘要
Current research has demonstrated that tumor development and progression are dependent on a multi-cellular interactome, which forms the tumor microenvironment. Multiple components of this multi-cellular ecosystem need to be targeted simultaneously for successful cancer therapy. The objective of this study was to develop a multidimensional combined chemo-immunotherapeutic modality for effective breast cancer treatment. TLR 7/8 agonist resiquimod was identified as a potent macrophage stimulant in an initial screening. To deliver paclitaxel as a chemotherapeutic drug and resiquimod as an immune activator in a tumor-targeted fashion, two different pH-sensitive nanoparticles were synthesized using two different polymers, a linear PLGA and a multi-arm, star-shaped PLGA. The star-PLGA pH-responsive nanoparticles exhibited improved pH-dependent drug release and increased penetration in a complex breast cancer spheroid model (breast cancer cell + macrophage cell). Treatment with paclitaxel and resiquimod encapsulated in the pH-responsive nanoparticles resulted in increased cancer cell death and macrophage activation, as tested in an in-vitro breast cancer spheroid model. Altogether, the current study suggests that the paclitaxel and resiquimod combination has potent chemo-immunotherapeutic activity, and delivery using a pH-sensitive nanoparticle further improves its efficacy.
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