1. Biomimetic nanoparticles loading with gamabutolin-indomethacin for chemo/photothermal therapy of cervical cancer and anti-inflammation.
- Author
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Xiao, Chang, Tong, Chunyi, Fan, Jialong, Wang, Zhou, Xie, Qian, Long, Ying, You, Peidong, Wang, Wei, and Liu, Bin
- Subjects
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CERVICAL cancer , *CANCER treatment , *TUMOR microenvironment , *TUMOR growth , *INDOMETHACIN , *NANOMEDICINE - Abstract
A pro-nanodrug combinational strategy for efficient cervical cancer therapy with intrinsic tumor microenvironment (TME)-responsive elements and low side effects is highly desired. Here, a pro-nanodrug complexes with GSH and NIR responsive manner is reported to boost gamabufotalin induced chemo-photothermal therapy with the assistance of reprogrammed TME by indomethacin. In addition, hybrid cell membrane was used to endow nanocomplexes with the prolonging circulation time and high accumulation of drug at tumor tissue. Indomethacin activated by the high level GSH can attenuate tumor inflammation microenvironment triggered by PTT and sensitize tumor cells to gamabufotalin through inhibiting PGE2 secretion. The released low-dose gamabufotalin with low side effects can efficiently kill tumor cells by ROS production and COX-2 low expression. In vitro and in vivo assays demonstrated that strong anti-tumor activity of nanocomplexes in tumor-bearing mice through chemo-photothermal therapy, which was reflected by the eradication of cervical tumor and significant extension of survival time of mice. We prepared the NIR and GSH sensitive nanocomplexes containing biomimetic membrane for synergistic tumor suppression by improving tumor microenvironment. CS-6 and IND were loaded on the inner and outer layers of PB by physical loading and chemical modification, respectively. The dual-drug combination therapy alleviated the inflammation triggered by PTT and enhanced the chemotherapeutic sensitivity of cancer cells by COX-2/PGE2 pathway inhibition. Finally, an RBC-Hela hybrid membrane endowed nanocomplexes with high targeting ability and biocompatibility. [Display omitted] • A GSH/NIR responsive biomimetic nanocomplexes containing gamabutolin and indomethacin was successfully constructed. • The synergy between the two drugs achieved effective tumor growth ablation and PTT-triggered inflammation suppression. • IND enhanced CS-6-induced chemotherapeutic sensitization by inhibiting PGE2 secretion. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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