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Chitosan-Based Hybrid Nanocomplex for siRNA Delivery and Its Application for Cancer Therapy

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Abstract

Purpose

Chitosan, a natural and biocompatible cationic polymer, is an attractive carrier for small interfering RNA (siRNA) delivery. The purpose of this study was to develop a chitosan-based hybrid nanocomplex that exhibits enhanced physical stability in the bloodstream compared with conventional chitosan complexes. Hybrid nanocomplexes composed of chitosan, protamine, lecithin, and thiamine pyrophosphate were prepared for systemic delivery of survivin (SVN) siRNA.

Methods

Physicochemical properties of the nanoparticles including mean diameters and zeta potentials were characterized, and target gene silencing and cellular uptake efficiencies of the siRNA nanocomplexes in prostate cancer cells (PC-3 cells) were measured. In vivo tumor targetability and anti-tumor efficacy by systemic administration were assessed in a PC-3 tumor xenograft mouse model by near-infrared fluorescence (NIRF) imaging and tumor growth monitoring, respectively.

Results

Mean diameters of the SVN siRNA-loaded hybrid nanocomplex (GP-L-CT) were less than 200 nm with a positive zeta potential value in water and were maintained without aggregation in culture media and 50% fetal bovine serum. SVN expression in PC-3 cells was reduced to 21.9% after treating with GP-L-CT. The tumor targetability and growth inhibitory efficacies of GP-L-CT supported the use of this novel hybrid nanocomplex as a cancer therapeutic and as a theranostic system for systemic administration.

Conclusions

A chitosan-based hybrid nanocomplex was successfully developed for the systemic delivery of SVN siRNA, which could serve as an alternative to cationic polymeric nanoparticles that are unstable in serum.

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Abbreviations

Cryo-TEM:

Cryo-transmission electron microscopy

EPR:

Enhanced permeability and retention

NIRF:

Near-infrared fluorescence

RNAi:

RNA interference

SCID:

Severe combined immunodeficiency

siRNA:

Small interfering ribonucleic acid

TPP:

Thiamine pyrophosphate

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported by the Ministry of Knowledge Economy of Korea (10030044, SM. Noh).

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Authors and Affiliations

  1. Chong Kun Dang Research Institute, Chong Kun Dang Pharm., Yongin, 446-916, Republic of Korea

    Min-Hyo Ki, Young-Nam Lee, Sang Myoung Noh & Sung-Won An

  2. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, Republic of Korea

    Min-Hyo Ki, Ji-Eon Kim & Dae-Duk Kim

  3. College of Pharmacy, Kangwon National University, Chuncheon, 200-701, Republic of Korea

    Hyun-Jong Cho

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  1. Min-Hyo Ki
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Correspondence to Dae-Duk Kim.

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Ki, MH., Kim, JE., Lee, YN. et al. Chitosan-Based Hybrid Nanocomplex for siRNA Delivery and Its Application for Cancer Therapy. Pharm Res 31, 3323–3334 (2014). https://doi.org/10.1007/s11095-014-1422-3

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  • DOI: https://doi.org/10.1007/s11095-014-1422-3

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