Preparation of pH-sensitive CaP nanoparticles coated with a phosphate-based block copolymer for efficient gene delivery

Sangmok Jang; Seonju Lee; Heejin Kim; Jiyeon Ham; Ji Hun Seo; Yeongbong Mok; Minwoo Noh; Yan Lee

doi:10.1016/j.polymer.2012.08.043

Preparation of pH-sensitive CaP nanoparticles coated with a phosphate-based block copolymer for efficient gene delivery

Sangmok Jang, Seonju Lee, Heejin Kim, Jiyeon Ham, Ji Hun Seo, Yeongbong Mok, Minwoo Noh, Yan Lee

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

Abstract

We have synthesized a phosphate-based block copolymer, PEG-b-PMOEP (poly(ethylene glycol)-b-poly(2-methacryloyloxyethyl phosphate)), with a narrow molecular weight distribution (PD = 1.06) by atomic transfer radical polymerization (ATRP), and have constructed calcium phosphate nanoparticles (CaPNs) coated with the block copolymer as an efficient and safe intracellular gene delivery carrier. The phosphate-mimic PMOEP block could be incorporated into the calcium phosphate (CaP) core to entrap pDNA, with the PEG block forming a shell to prevent uncontrolled growth of CaP precipitates and aggregates in physiological fluids. The CaPNs showed high colloidal stability at pH 7.4, but released entrapped pDNA at an endosomal pH of 5.0 through a pH-dependent protonation of phosphate moieties for efficient endosomal escape. The PEG-b-PMOEP/CaP/pDNA nanoparticles, which were formed simply by mixing, exhibited great potential as gene delivery carriers for future gene therapy applications due to their high transfection efficiency, low toxicity, and good stability under physiological conditions.

Original language	English
Pages (from-to)	4678-4685
Number of pages	8
Journal	Polymer
Volume	53
Issue number	21
DOIs	https://doi.org/10.1016/j.polymer.2012.08.043
Publication status	Published - 2012 Sept 28
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by the Basic Science Research Program ( 2011-0002301 ) through the National Research Foundation (NRF) funded by the Ministry of Education, Science, and Technology of Korea and Seoul R&BD program ( ST110017M0209721 ).

Keywords

Block copolymer
Calcium phosphate
pH-sensitivity

ASJC Scopus subject areas

Organic Chemistry
Polymers and Plastics
Materials Chemistry

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10.1016/j.polymer.2012.08.043

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title = "Preparation of pH-sensitive CaP nanoparticles coated with a phosphate-based block copolymer for efficient gene delivery",

abstract = "We have synthesized a phosphate-based block copolymer, PEG-b-PMOEP (poly(ethylene glycol)-b-poly(2-methacryloyloxyethyl phosphate)), with a narrow molecular weight distribution (PD = 1.06) by atomic transfer radical polymerization (ATRP), and have constructed calcium phosphate nanoparticles (CaPNs) coated with the block copolymer as an efficient and safe intracellular gene delivery carrier. The phosphate-mimic PMOEP block could be incorporated into the calcium phosphate (CaP) core to entrap pDNA, with the PEG block forming a shell to prevent uncontrolled growth of CaP precipitates and aggregates in physiological fluids. The CaPNs showed high colloidal stability at pH 7.4, but released entrapped pDNA at an endosomal pH of 5.0 through a pH-dependent protonation of phosphate moieties for efficient endosomal escape. The PEG-b-PMOEP/CaP/pDNA nanoparticles, which were formed simply by mixing, exhibited great potential as gene delivery carriers for future gene therapy applications due to their high transfection efficiency, low toxicity, and good stability under physiological conditions.",

keywords = "Block copolymer, Calcium phosphate, pH-sensitivity",

author = "Sangmok Jang and Seonju Lee and Heejin Kim and Jiyeon Ham and Seo, {Ji Hun} and Yeongbong Mok and Minwoo Noh and Yan Lee",

note = "Funding Information: This work was supported by the Basic Science Research Program ( 2011-0002301 ) through the National Research Foundation (NRF) funded by the Ministry of Education, Science, and Technology of Korea and Seoul R&BD program ( ST110017M0209721 ). ",

year = "2012",

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doi = "10.1016/j.polymer.2012.08.043",

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T1 - Preparation of pH-sensitive CaP nanoparticles coated with a phosphate-based block copolymer for efficient gene delivery

AU - Jang, Sangmok

AU - Lee, Seonju

AU - Kim, Heejin

AU - Ham, Jiyeon

AU - Seo, Ji Hun

AU - Mok, Yeongbong

AU - Noh, Minwoo

AU - Lee, Yan

N1 - Funding Information: This work was supported by the Basic Science Research Program ( 2011-0002301 ) through the National Research Foundation (NRF) funded by the Ministry of Education, Science, and Technology of Korea and Seoul R&BD program ( ST110017M0209721 ).

PY - 2012/9/28

Y1 - 2012/9/28

N2 - We have synthesized a phosphate-based block copolymer, PEG-b-PMOEP (poly(ethylene glycol)-b-poly(2-methacryloyloxyethyl phosphate)), with a narrow molecular weight distribution (PD = 1.06) by atomic transfer radical polymerization (ATRP), and have constructed calcium phosphate nanoparticles (CaPNs) coated with the block copolymer as an efficient and safe intracellular gene delivery carrier. The phosphate-mimic PMOEP block could be incorporated into the calcium phosphate (CaP) core to entrap pDNA, with the PEG block forming a shell to prevent uncontrolled growth of CaP precipitates and aggregates in physiological fluids. The CaPNs showed high colloidal stability at pH 7.4, but released entrapped pDNA at an endosomal pH of 5.0 through a pH-dependent protonation of phosphate moieties for efficient endosomal escape. The PEG-b-PMOEP/CaP/pDNA nanoparticles, which were formed simply by mixing, exhibited great potential as gene delivery carriers for future gene therapy applications due to their high transfection efficiency, low toxicity, and good stability under physiological conditions.

AB - We have synthesized a phosphate-based block copolymer, PEG-b-PMOEP (poly(ethylene glycol)-b-poly(2-methacryloyloxyethyl phosphate)), with a narrow molecular weight distribution (PD = 1.06) by atomic transfer radical polymerization (ATRP), and have constructed calcium phosphate nanoparticles (CaPNs) coated with the block copolymer as an efficient and safe intracellular gene delivery carrier. The phosphate-mimic PMOEP block could be incorporated into the calcium phosphate (CaP) core to entrap pDNA, with the PEG block forming a shell to prevent uncontrolled growth of CaP precipitates and aggregates in physiological fluids. The CaPNs showed high colloidal stability at pH 7.4, but released entrapped pDNA at an endosomal pH of 5.0 through a pH-dependent protonation of phosphate moieties for efficient endosomal escape. The PEG-b-PMOEP/CaP/pDNA nanoparticles, which were formed simply by mixing, exhibited great potential as gene delivery carriers for future gene therapy applications due to their high transfection efficiency, low toxicity, and good stability under physiological conditions.

KW - Block copolymer

KW - Calcium phosphate

KW - pH-sensitivity

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DO - 10.1016/j.polymer.2012.08.043

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Preparation of pH-sensitive CaP nanoparticles coated with a phosphate-based block copolymer for efficient gene delivery

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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