Polycation-functionalized nanoporous silicon particles for gene silencing on breast cancer cells

Mingzhen Zhang; Rong Xu; Xiaojun Xia; Yong Yang; Jianhua Gu; Guoting Qin; Xuewu Liu; Mauro Ferrari; Haifa Shen

doi:10.1016/j.biomaterials.2013.09.033

Polycation-functionalized nanoporous silicon particles for gene silencing on breast cancer cells

Mingzhen Zhang, Rong Xu, Xiaojun Xia, Yong Yang, Jianhua Gu, Guoting Qin, Xuewu Liu, Mauro Ferrari, Haifa Shen

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

44 Scopus citations

Abstract

Nanoporous silicon particles (pSi), with a pore size in the range of 20-60nm, were modified with polyethyleneimine (PEI) to yield pSi-PEI particles, which were subsequently complexed with siRNA. Thus, pSi-PEI/siRNA particles were fabricated, with the PEI/siRNA nanocomplexes mainly anchored inside the nanopore of the pSi particles. These hybrid particles were used as carriers to deliver siRNA to human breast cancer cells. Due to the gradual degradation of the pSi matrix under physiological conditions, the PEI/siRNA nanocomplexes were released from the pore interior in a sustained manner. Physicochemical characterization revealed that the released PEI/siRNA nanocomplexes exhibited well-defined spherical shape and narrow particle size distribution between 15 and 30nm. Gene knockdown against the ataxia telangiectasia mutated (ATM) cancer gene showed dramatic gene silencing efficacy. Moreover, comprehensive biocompatibility studies were performed for the pSi-PEI/siRNA particles both invitro and invivo and demonstrated that the pSi-PEI particles exhibited significantly enhanced biocompatibility. As a consequence, PEI-modified porous silicon particles may have substantial potential as safe and effective siRNA delivery systems.

Original language	English (US)
Pages (from-to)	423-431
Number of pages	9
Journal	Biomaterials
Volume	35
Issue number	1
DOIs	https://doi.org/10.1016/j.biomaterials.2013.09.033
State	Published - 2014

Keywords

Breast cancer
Non-viral gene delivery
Polyplex
Porous silicon particles
SiRNA

ASJC Scopus subject areas

Biomaterials
Bioengineering
Ceramics and Composites
Mechanics of Materials
Biophysics

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10.1016/j.biomaterials.2013.09.033

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@article{234fc46aba2c42b0baf9a0c1c03b1511,

title = "Polycation-functionalized nanoporous silicon particles for gene silencing on breast cancer cells",

abstract = "Nanoporous silicon particles (pSi), with a pore size in the range of 20-60nm, were modified with polyethyleneimine (PEI) to yield pSi-PEI particles, which were subsequently complexed with siRNA. Thus, pSi-PEI/siRNA particles were fabricated, with the PEI/siRNA nanocomplexes mainly anchored inside the nanopore of the pSi particles. These hybrid particles were used as carriers to deliver siRNA to human breast cancer cells. Due to the gradual degradation of the pSi matrix under physiological conditions, the PEI/siRNA nanocomplexes were released from the pore interior in a sustained manner. Physicochemical characterization revealed that the released PEI/siRNA nanocomplexes exhibited well-defined spherical shape and narrow particle size distribution between 15 and 30nm. Gene knockdown against the ataxia telangiectasia mutated (ATM) cancer gene showed dramatic gene silencing efficacy. Moreover, comprehensive biocompatibility studies were performed for the pSi-PEI/siRNA particles both invitro and invivo and demonstrated that the pSi-PEI particles exhibited significantly enhanced biocompatibility. As a consequence, PEI-modified porous silicon particles may have substantial potential as safe and effective siRNA delivery systems.",

keywords = "Breast cancer, Non-viral gene delivery, Polyplex, Porous silicon particles, SiRNA",

author = "Mingzhen Zhang and Rong Xu and Xiaojun Xia and Yong Yang and Jianhua Gu and Guoting Qin and Xuewu Liu and Mauro Ferrari and Haifa Shen",

note = "Funding Information: The authors acknowledge Asad Moten, a visiting doctoral student at the Department of Primary Care Health Sciences and Nuffield Department of Clinical Medicine at the University of Oxford (UK) for his help in editing the manuscript. This work was supported by Department of Defense grants W81XWH-09-1-0212 and W81XWH-12-1-0414 , National Institute of Health grants U54CA143837 and U54CA151668 , the State of Texas CPRIT grant RP121071 , and the Ernest Cockrell Jr. Distinguished Endowed Chair . Financial support from the NSFC (grant number: 51173035 ) is also acknowledged (M.Z.). The authors do not disclose any potential conflicts of interest.",

year = "2014",

doi = "10.1016/j.biomaterials.2013.09.033",

language = "English (US)",

volume = "35",

pages = "423--431",

journal = "Biomaterials",

issn = "0142-9612",

publisher = "Elsevier BV",

number = "1",

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TY - JOUR

T1 - Polycation-functionalized nanoporous silicon particles for gene silencing on breast cancer cells

AU - Zhang, Mingzhen

AU - Xu, Rong

AU - Xia, Xiaojun

AU - Yang, Yong

AU - Gu, Jianhua

AU - Qin, Guoting

AU - Liu, Xuewu

AU - Ferrari, Mauro

AU - Shen, Haifa

N1 - Funding Information: The authors acknowledge Asad Moten, a visiting doctoral student at the Department of Primary Care Health Sciences and Nuffield Department of Clinical Medicine at the University of Oxford (UK) for his help in editing the manuscript. This work was supported by Department of Defense grants W81XWH-09-1-0212 and W81XWH-12-1-0414 , National Institute of Health grants U54CA143837 and U54CA151668 , the State of Texas CPRIT grant RP121071 , and the Ernest Cockrell Jr. Distinguished Endowed Chair . Financial support from the NSFC (grant number: 51173035 ) is also acknowledged (M.Z.). The authors do not disclose any potential conflicts of interest.

PY - 2014

Y1 - 2014

N2 - Nanoporous silicon particles (pSi), with a pore size in the range of 20-60nm, were modified with polyethyleneimine (PEI) to yield pSi-PEI particles, which were subsequently complexed with siRNA. Thus, pSi-PEI/siRNA particles were fabricated, with the PEI/siRNA nanocomplexes mainly anchored inside the nanopore of the pSi particles. These hybrid particles were used as carriers to deliver siRNA to human breast cancer cells. Due to the gradual degradation of the pSi matrix under physiological conditions, the PEI/siRNA nanocomplexes were released from the pore interior in a sustained manner. Physicochemical characterization revealed that the released PEI/siRNA nanocomplexes exhibited well-defined spherical shape and narrow particle size distribution between 15 and 30nm. Gene knockdown against the ataxia telangiectasia mutated (ATM) cancer gene showed dramatic gene silencing efficacy. Moreover, comprehensive biocompatibility studies were performed for the pSi-PEI/siRNA particles both invitro and invivo and demonstrated that the pSi-PEI particles exhibited significantly enhanced biocompatibility. As a consequence, PEI-modified porous silicon particles may have substantial potential as safe and effective siRNA delivery systems.

AB - Nanoporous silicon particles (pSi), with a pore size in the range of 20-60nm, were modified with polyethyleneimine (PEI) to yield pSi-PEI particles, which were subsequently complexed with siRNA. Thus, pSi-PEI/siRNA particles were fabricated, with the PEI/siRNA nanocomplexes mainly anchored inside the nanopore of the pSi particles. These hybrid particles were used as carriers to deliver siRNA to human breast cancer cells. Due to the gradual degradation of the pSi matrix under physiological conditions, the PEI/siRNA nanocomplexes were released from the pore interior in a sustained manner. Physicochemical characterization revealed that the released PEI/siRNA nanocomplexes exhibited well-defined spherical shape and narrow particle size distribution between 15 and 30nm. Gene knockdown against the ataxia telangiectasia mutated (ATM) cancer gene showed dramatic gene silencing efficacy. Moreover, comprehensive biocompatibility studies were performed for the pSi-PEI/siRNA particles both invitro and invivo and demonstrated that the pSi-PEI particles exhibited significantly enhanced biocompatibility. As a consequence, PEI-modified porous silicon particles may have substantial potential as safe and effective siRNA delivery systems.

KW - Breast cancer

KW - Non-viral gene delivery

KW - Polyplex

KW - Porous silicon particles

KW - SiRNA

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VL - 35

SP - 423

EP - 431

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 1

ER -

Polycation-functionalized nanoporous silicon particles for gene silencing on breast cancer cells

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