Bioengineered protein nanocage by small heat shock proteins delivering mTERT siRNA for enhanced colorectal cancer suppression

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Wang, Hao and Liu, Ning and Yang, Fuxu and Hu, Nannan and Wang, Mingyue and Cui, Meiying and Bruns, Nico and Guan, Xingang (2022) Bioengineered protein nanocage by small heat shock proteins delivering mTERT siRNA for enhanced colorectal cancer suppression. ACS Applied Bio Materials, 5 (3). pp. 1330-1340. ISSN 2576-6422 (https://doi.org/10.1021/acsabm.1c01221)

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Abstract

The efficient delivery of small interfering RNA (siRNA) for target gene silencing holds great promise for cancer therapy. Protein nanocages have attracted considerable attention as ideal drug delivery systems because of their material-derived advantages and unique structural properties. However, most studies about siRNA delivery have not indicated the real role of protein nanocages in inhibiting tumor growth in vivo. Herein, we fabricated an efficient siRNA delivery system using a small heat shock protein (Hsp) nanocage decorated with Arg-Gly-Asp (RGD) and the transactivator of transcription (Tat) peptide. Hsp-Tat-RGD NC showed good cellular uptake and lysosomal escape in colorectal cancer cells. In addition, the nanocage could efficiently transfect siRNA into the cytoplasmic area of CT26 cells. Hsp-Tat-RGD NC delivering telomerase reverse transcriptase (TERT)-targeting siRNA could significantly downregulate TERT protein expression and trigger tumor cell apoptosis in vitro. More importantly, Hsp-Tat-RGD/siTERT complexes nearly completely inhibited the tumor growth after five times of treatment in mice bearing CT26 xenograft. Our results demonstrate the great potential of the Tat/RGD-decorated Hsp nanocage as a promising siRNA delivery platform for cancer therapy.

ORCID iDs

Wang, Hao, Liu, Ning, Yang, Fuxu, Hu, Nannan, Wang, Mingyue, Cui, Meiying, Bruns, Nico ORCID logoORCID: https://orcid.org/0000-0001-6199-9995 and Guan, Xingang;
  • Item type:Article
    ID code:79886
    Dates:
    Date
    Event
    21 March 2022
    Published
    2 March 2022
    Published Online
    20 February 2022
    Accepted
    Subjects:Science > Chemistry
    Department:Faculty of Science > Pure and Applied Chemistry
    Depositing user: Pure Administrator
    Date deposited:15 Mar 2022 13:17
    Last modified:27 Nov 2024 01:20
    URI:https://strathprints.strath.ac.uk/id/eprint/79886
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