Abstract |
Small active RNA (saRNA)-induced gene activation (RNAa) is a novel strategy to treat cancer. Our previous work proved that the p21-saRNA-322 successfully hindered colorectal cancer growth by activating p21 gene. However, the barrier for successful saRNA therapy is lack of efficient drug delivery. In the present study, a rectal delivery system entitled p21-saRNA-322 encapsulated tumor-selective lipopolyplex (TSLPP-p21-saRNA-322) which consist of PEI/p21-saRNA-322 polyplex core and hyaluronan (HA) modulated lipid shell was developed to treat colorectal cancer. Our results showed that this system maintained at the rectum for more than 6 h and preferentially accumulated at tumor site. CD44 knock down experiment instructed that the superb cellular uptake of TSLPP-p21-saRNA-322 attributed to HA-CD44 recognition. An orthotopic model of bio-luminescence human colorectal cancer in mice was developed using microsurgery and TSLPP-p21-saRNA-322 demonstrated a superior antitumor efficacy in vitro and in vivo. Our results provide preclinical proof-of-concept for a novel method to treat colorectal cancer by rectal administration of TSLPP formulated p21-saRNA-322.
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Authors | Lu-Lu Wang, Chen-Lin Feng, Wen-Sheng Zheng, Shuai Huang, Wen-Xuan Zhang, Hong-Na Wu, Yun Zhan, Yan-Xing Han, Song Wu, Jian-Dong Jiang |
Journal | Biomaterials
(Biomaterials)
Vol. 141
Pg. 13-28
(Oct 2017)
ISSN: 1878-5905 [Electronic] Netherlands |
PMID | 28666099
(Publication Type: Journal Article)
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Copyright | Copyright © 2017 Elsevier Ltd. All rights reserved. |
Chemical References |
- Cyclin-Dependent Kinase Inhibitor p21
- Hyaluronan Receptors
- Lipids
- RNA
- Hyaluronic Acid
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Topics |
- Animals
- Cell Cycle
- Colon
(metabolism, pathology)
- Colorectal Neoplasms
(genetics, pathology, therapy)
- Cyclin-Dependent Kinase Inhibitor p21
(genetics)
- Drug Delivery Systems
(methods)
- Gene Transfer Techniques
- Genetic Therapy
(methods)
- HT29 Cells
- Humans
- Hyaluronan Receptors
(genetics)
- Hyaluronic Acid
(analogs & derivatives)
- Lipids
(chemistry)
- Male
- Mice
- Mice, Inbred NOD
- Mice, SCID
- RNA
(administration & dosage, genetics, therapeutic use)
- Rectum
(metabolism, pathology)
- Transcriptional Activation
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