Abstract | BACKGROUND: Drugs that work based on the mechanism of RNA interference have shown strong potential in cancer gene therapy. Although significant progress has been made in small interfering RNA ( siRNA) design and manufacturing, ideal delivery system remains a limitation for the development of siRNA-based drugs. Particularly, it is necessary to focus on parameters including delivery efficiency, stability, and safety when developing siRNA formulations for cancer therapy. METHODS: RESULTS: The synthesized rrPPC was dispersed as nanoparticles in water with an average size of 195 nm and 41.9 mV in potential. rrPPC nanoparticles could efficiently deliver siRNA into C26 clone cancer cells and trigger caveolae-mediated pathway during transmembrane transportation. By loading the signal transducer and activator of transcription 3 (STAT3) targeting siRNA, rrPPC/STAT3 siRNA (rrPPC/siSTAT3) complex demonstrated strong anti- cancer effects in multiple colon cancer models following local delivery. In addition, intravenous (IV) injection of rrPPC/siSTAT3 complex efficiently suppressed lung metastasis tumor progression with ideal in vivo safety. CONCLUSION: Our results provide evidence that rrPPC nanoparticles constitute a potential candidate vector for siRNA-based colon cancer gene therapy.
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Authors | Hongjia Zhang, Ke Men, Congbin Pan, Yan Gao, Jingmei Li, Sibei Lei, Guonian Zhu, Rui Li, Yuquan Wei, Xingmei Duan |
Journal | International journal of nanomedicine
(Int J Nanomedicine)
Vol. 15
Pg. 9875-9890
( 2020)
ISSN: 1178-2013 [Electronic] New Zealand |
PMID | 33324056
(Publication Type: Journal Article)
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Copyright | © 2020 Zhang et al. |
Chemical References |
- Drug Carriers
- Peptides, Cyclic
- RNA, Small Interfering
- STAT3 Transcription Factor
- STAT3 protein, human
- cyclic arginine-glycine-aspartic acid peptide
- poly(ethylene glycol)-co-poly(ethyleneimine)
- Polyethylene Glycols
- Polyethyleneimine
- Cholesterol
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Topics |
- Cell Line, Tumor
- Cholesterol
(chemistry)
- Colonic Neoplasms
(genetics, therapy)
- Drug Carriers
(chemistry)
- Humans
- Nanoparticles
(chemistry)
- Peptides, Cyclic
(chemistry)
- Polyethylene Glycols
(chemistry)
- Polyethyleneimine
(analogs & derivatives, chemistry)
- RNA Interference
- RNA, Small Interfering
(chemistry, genetics)
- STAT3 Transcription Factor
(deficiency, genetics)
- Transfection
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