Chitosan-Crosslinked Low Molecular Weight PEI-Conjugated Iron Oxide Nanoparticle for Safe and Effective DNA Delivery to Breast Cancer Cells

Breast cancer has attracted tremendous research interest in treatment development as one of the major threats to public health. The use of non-viral carriers for therapeutic DNA delivery has shown promise in treating various cancer types, including breast cancer, due to their high DNA loading capaci...

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Main Authors: Guanyou Lin, Jianxi Huang, Mengyuan Zhang, Shanshan Chen, Miqin Zhang
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Nanomaterials
Subjects:
Online Access:https://www.mdpi.com/2079-4991/12/4/584
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author Guanyou Lin
Jianxi Huang
Mengyuan Zhang
Shanshan Chen
Miqin Zhang
author_facet Guanyou Lin
Jianxi Huang
Mengyuan Zhang
Shanshan Chen
Miqin Zhang
author_sort Guanyou Lin
collection DOAJ
description Breast cancer has attracted tremendous research interest in treatment development as one of the major threats to public health. The use of non-viral carriers for therapeutic DNA delivery has shown promise in treating various cancer types, including breast cancer, due to their high DNA loading capacity, high cell transfection efficiency, and design versatility. However, cytotoxicity and large sizes of non-viral DNA carriers often raise safety concerns and hinder their applications in the clinic. Here we report the development of a novel nanoparticle formulation (termed NP-Chi-xPEI) that can safely and effectively deliver DNA into breast cancer cells for successful transfection. The nanoparticle is composed of an iron oxide core coated with low molecular weight (800 Da) polyethyleneimine crosslinked with chitosan via biodegradable disulfide bonds. The NP-Chi-xPEI can condense DNA into a small nanoparticle with the overall size of less than 100 nm and offer full DNA protection. Its biodegradable coating of small-molecular weight xPEI and mildly positive surface charge confer extra biocompatibility. NP-Chi-xPEI-mediated DNA delivery was shown to achieve high transfection efficiency across multiple breast cancer cell lines with significantly lower cytotoxicity as compared to the commercial transfection agent Lipofectamine 3000. With demonstrated favorable physicochemical properties and functionality, NP-Chi-xPEI may serve as a reliable vehicle to deliver DNA to breast cancer cells.
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spelling doaj.art-ebb26dac40ce40ed965657f6010671652023-11-23T21:24:56ZengMDPI AGNanomaterials2079-49912022-02-0112458410.3390/nano12040584Chitosan-Crosslinked Low Molecular Weight PEI-Conjugated Iron Oxide Nanoparticle for Safe and Effective DNA Delivery to Breast Cancer CellsGuanyou Lin0Jianxi Huang1Mengyuan Zhang2Shanshan Chen3Miqin Zhang4Department of Materials Science and Engineering, University of Washington, Seattle, WA 98195, USADepartment of Materials Science and Engineering, University of Washington, Seattle, WA 98195, USADepartment of Materials Science and Engineering, University of Washington, Seattle, WA 98195, USADepartment of Materials Science and Engineering, University of Washington, Seattle, WA 98195, USADepartment of Materials Science and Engineering, University of Washington, Seattle, WA 98195, USABreast cancer has attracted tremendous research interest in treatment development as one of the major threats to public health. The use of non-viral carriers for therapeutic DNA delivery has shown promise in treating various cancer types, including breast cancer, due to their high DNA loading capacity, high cell transfection efficiency, and design versatility. However, cytotoxicity and large sizes of non-viral DNA carriers often raise safety concerns and hinder their applications in the clinic. Here we report the development of a novel nanoparticle formulation (termed NP-Chi-xPEI) that can safely and effectively deliver DNA into breast cancer cells for successful transfection. The nanoparticle is composed of an iron oxide core coated with low molecular weight (800 Da) polyethyleneimine crosslinked with chitosan via biodegradable disulfide bonds. The NP-Chi-xPEI can condense DNA into a small nanoparticle with the overall size of less than 100 nm and offer full DNA protection. Its biodegradable coating of small-molecular weight xPEI and mildly positive surface charge confer extra biocompatibility. NP-Chi-xPEI-mediated DNA delivery was shown to achieve high transfection efficiency across multiple breast cancer cell lines with significantly lower cytotoxicity as compared to the commercial transfection agent Lipofectamine 3000. With demonstrated favorable physicochemical properties and functionality, NP-Chi-xPEI may serve as a reliable vehicle to deliver DNA to breast cancer cells.https://www.mdpi.com/2079-4991/12/4/584iron oxide nanoparticlesgene therapybreast cancer
spellingShingle Guanyou Lin
Jianxi Huang
Mengyuan Zhang
Shanshan Chen
Miqin Zhang
Chitosan-Crosslinked Low Molecular Weight PEI-Conjugated Iron Oxide Nanoparticle for Safe and Effective DNA Delivery to Breast Cancer Cells
Nanomaterials
iron oxide nanoparticles
gene therapy
breast cancer
title Chitosan-Crosslinked Low Molecular Weight PEI-Conjugated Iron Oxide Nanoparticle for Safe and Effective DNA Delivery to Breast Cancer Cells
title_full Chitosan-Crosslinked Low Molecular Weight PEI-Conjugated Iron Oxide Nanoparticle for Safe and Effective DNA Delivery to Breast Cancer Cells
title_fullStr Chitosan-Crosslinked Low Molecular Weight PEI-Conjugated Iron Oxide Nanoparticle for Safe and Effective DNA Delivery to Breast Cancer Cells
title_full_unstemmed Chitosan-Crosslinked Low Molecular Weight PEI-Conjugated Iron Oxide Nanoparticle for Safe and Effective DNA Delivery to Breast Cancer Cells
title_short Chitosan-Crosslinked Low Molecular Weight PEI-Conjugated Iron Oxide Nanoparticle for Safe and Effective DNA Delivery to Breast Cancer Cells
title_sort chitosan crosslinked low molecular weight pei conjugated iron oxide nanoparticle for safe and effective dna delivery to breast cancer cells
topic iron oxide nanoparticles
gene therapy
breast cancer
url https://www.mdpi.com/2079-4991/12/4/584
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