Chemo-immunotherapy of colon cancer with focused ultrasound and Salmonella-laden temperature sensitive liposomes (thermobots).

Chemo-immunotherapy of colon cancer with focused ultrasound and Salmonella-laden temperature sensitive liposomes (thermobots).
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DOI:
10.1038/s41598-018-30106-4
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发表时间:
2018-08-30
期刊:
影响因子:
4.6
通讯作者:
Ranjan A
Ranjan A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ektate K;Munteanu MC;Ashar H;Malayer J;Ranjan A

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利用在实体肿瘤中有效聚集的减毒沙门氏菌,我们开发了一种热机器人,可以在结肠癌细胞内主动运输膜附着的低温敏感脂质体(LTSL),触发阿霉素释放,并在高强度聚焦超声(HIFU)加热(40-42°C)的情况下同时极化巨噬细胞到M1表型。生物相容性研究表明,合成的热机器人在不影响LTSL生存能力的情况下具有很高的负载效率。在体外实验中,热机器人在结肠癌细胞中表现出高效的细胞内运输,高阿霉素核定位,并诱导促炎细胞因子的表达。与对照组相比,热机器人联合HIFU加热(~ 30min)可显著增强小鼠结肠肿瘤巨噬细胞对M1表型的极化和体内治疗效果。我们的数据表明,热机器人和聚焦超声治疗有可能改善结肠癌的治疗。
Using attenuated Salmonella that efficiently homes in solid tumors, here we developed thermobots that actively transported membrane attached low-temperature sensitive liposome (LTSL) inside colon cancer cells for triggered doxorubicin release and simultaneous polarized macrophages to M1 phenotype with high intensity focused ultrasound (HIFU) heating (40–42 °C). Biocompatibility studies showed that the synthesized thermobots were highly efficient in LTSL loading without impacting its viability. Thermobots demonstrated efficient intracellular trafficking, high nuclear localization of doxorubicin, and induced pro-inflammatory cytokine expression in colon cancer cells in vitro. Combination of thermobots and HIFU heating (~30 min) in murine colon tumors significantly enhanced polarization of macrophages to M1 phenotype and therapeutic efficacy in vivo compared to control. Our data suggest that the thermobots and focused ultrasound treatments have the potential to improve colon cancer therapy.
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