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Tumor-selective lipopolyplex encapsulated small active RNA hampers colorectal cancer growth in vitro and in orthotopic murine.

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.
AuthorsLu-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
JournalBiomaterials (Biomaterials) Vol. 141 Pg. 13-28 (Oct 2017) ISSN: 1878-5905 [Electronic] Netherlands
PMID28666099 (Publication Type: Journal Article)
CopyrightCopyright © 2017 Elsevier Ltd. All rights reserved.
Chemical References
  • Cyclin-Dependent Kinase Inhibitor p21
  • Hyaluronan Receptors
  • Lipids
  • RNA
  • Hyaluronic Acid
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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