Systemic siRNA delivery to a spontaneous pancreatic tumor model in transgenic mice by PEGylated calcium phosphate hybrid micelles

Efficient systems for delivery of small interfering RNA (siRNA) are required for clinical application of RNA interference (RNAi) in cancer therapy. Herein, we developed a safe and efficient nanocarrier comprising poly(ethylene glycol)-block-charge-conversional polymer (PEG-CCP)/calcium phosphate (Ca...

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Bibliographic Details
Published in:Journal of controlled release 2014-03, Vol.178, p.18-24
Main Authors: Pittella, Frederico, Cabral, Horacio, Maeda, Yoshinori, Mi, Peng, Watanabe, Sumiyo, Takemoto, Hiroyasu, Kim, Hyun Jin, Nishiyama, Nobuhiro, Miyata, Kanjiro, Kataoka, Kazunori
Format: Article
Language:English
Subjects:
Animals
Calcium phosphate
Calcium Phosphates - chemistry
Cell Line, Tumor
Charge-conversional polymer
Gene Silencing
Luciferases - genetics
Male
Mice
Mice, Transgenic
Micelles
Nanoparticles - administration & dosage
Nanoparticles - chemistry
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - metabolism
PEG
Polyethylene Glycols - chemistry
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - pharmacokinetics
siRNA delivery
Spontaneous pancreatic carcinoma
Tissue Distribution
Transgenic mice
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Summary:Efficient systems for delivery of small interfering RNA (siRNA) are required for clinical application of RNA interference (RNAi) in cancer therapy. Herein, we developed a safe and efficient nanocarrier comprising poly(ethylene glycol)-block-charge-conversional polymer (PEG-CCP)/calcium phosphate (CaP) hybrid micelles for systemic delivery of siRNA and studied their efficacy in spontaneous bioluminescent pancreatic tumors from transgenic mice. PEG-CCP was engineered to provide the siRNA-loaded hybrid micelles with enhanced colloidal stability and biocompatibility due to the PEG capsule and with endosome-disrupting functionality due to the acidic pH-responsive CCP segment where the polyanionic structure could be converted to polycationic structure at acidic pH through cis-aconitic amide cleavage. The resulting hybrid micelles were confirmed to have a diameter of
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2014.01.008