PAMAM-Functionalized Cellulose Nanocrystals with Needle-Like Morphology for Effective Cancer Treatment

Gene therapy is used to correct or compensate for diseases caused by gene defects and abnormalities. Improving the transfection efficiency and reducing the toxicity of gene carriers are the keys to gene therapy. Similar to a typical cationic gene carrier—polyethylenimine (PEI, 25 kDa)—the polyamidoa...

Full description

Bibliographic Details
Main Authors: Yanzhen Sun, Xiaoli Ma, Xiaodong Jing, Hao Hu
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Nanomaterials
Subjects:
Online Access:https://www.mdpi.com/2079-4991/11/7/1640
_version_ 1797529183392366592
author Yanzhen Sun
Xiaoli Ma
Xiaodong Jing
Hao Hu
author_facet Yanzhen Sun
Xiaoli Ma
Xiaodong Jing
Hao Hu
author_sort Yanzhen Sun
collection DOAJ
description Gene therapy is used to correct or compensate for diseases caused by gene defects and abnormalities. Improving the transfection efficiency and reducing the toxicity of gene carriers are the keys to gene therapy. Similar to a typical cationic gene carrier—polyethylenimine (PEI, 25 kDa)—the polyamidoamine (PAMAM) dendrimer also has a large number of amino groups. These amino groups can be complexed with nucleic acids after protonation under physiological conditions. However, the concentrated positive charge can cause undesirable cytotoxicity. Cellulose nanocrystals (CNCs) have good biocompatibility and unique needle-like morphology, and have been proven to be efficiently taken up by cells. In this article, three-dimensional spherical PMAMA dendrimers are conjugated onto the surface of CNCs to obtain a kind of needle-like cationic carrier (CNC-PAMAM). PAMAM dendrimers act as anchors to bind the plasmid DNAs (pDNA) to the surface of the CNC. The prepared CNC-based carrier showed high transfection efficiency and low toxicity. The CNC-PAMAM can effectively deliver the suicide gene to the tumor site, enabling the suicide gene/prodrug system (cytosine deaminase/5-fluorocytosine (CD/5-FC)) to play an effective anti-tumor role in vivo. This research demonstrates that the functionalization of CNCs with PAMAM dendrimers is an effective method for developing novel gene delivery systems.
first_indexed 2024-03-10T10:10:07Z
format Article
id doaj.art-d4652e7730a24868943cc10068dbf688
institution Directory Open Access Journal
issn 2079-4991
language English
last_indexed 2024-03-10T10:10:07Z
publishDate 2021-06-01
publisher MDPI AG
record_format Article
series Nanomaterials
spelling doaj.art-d4652e7730a24868943cc10068dbf6882023-11-22T01:17:23ZengMDPI AGNanomaterials2079-49912021-06-01117164010.3390/nano11071640PAMAM-Functionalized Cellulose Nanocrystals with Needle-Like Morphology for Effective Cancer TreatmentYanzhen Sun0Xiaoli Ma1Xiaodong Jing2Hao Hu3Institute of Biomedical Materials and Engineering, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, ChinaQingdao Institute of Measurement Technology, Qingdao 266000, ChinaInstitute of Biomedical Materials and Engineering, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, ChinaInstitute of Biomedical Materials and Engineering, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, ChinaGene therapy is used to correct or compensate for diseases caused by gene defects and abnormalities. Improving the transfection efficiency and reducing the toxicity of gene carriers are the keys to gene therapy. Similar to a typical cationic gene carrier—polyethylenimine (PEI, 25 kDa)—the polyamidoamine (PAMAM) dendrimer also has a large number of amino groups. These amino groups can be complexed with nucleic acids after protonation under physiological conditions. However, the concentrated positive charge can cause undesirable cytotoxicity. Cellulose nanocrystals (CNCs) have good biocompatibility and unique needle-like morphology, and have been proven to be efficiently taken up by cells. In this article, three-dimensional spherical PMAMA dendrimers are conjugated onto the surface of CNCs to obtain a kind of needle-like cationic carrier (CNC-PAMAM). PAMAM dendrimers act as anchors to bind the plasmid DNAs (pDNA) to the surface of the CNC. The prepared CNC-based carrier showed high transfection efficiency and low toxicity. The CNC-PAMAM can effectively deliver the suicide gene to the tumor site, enabling the suicide gene/prodrug system (cytosine deaminase/5-fluorocytosine (CD/5-FC)) to play an effective anti-tumor role in vivo. This research demonstrates that the functionalization of CNCs with PAMAM dendrimers is an effective method for developing novel gene delivery systems.https://www.mdpi.com/2079-4991/11/7/1640cellulose nanocrystalsPAMAM dendrimercationic gene carriergene transfectiongene therapy
spellingShingle Yanzhen Sun
Xiaoli Ma
Xiaodong Jing
Hao Hu
PAMAM-Functionalized Cellulose Nanocrystals with Needle-Like Morphology for Effective Cancer Treatment
Nanomaterials
cellulose nanocrystals
PAMAM dendrimer
cationic gene carrier
gene transfection
gene therapy
title PAMAM-Functionalized Cellulose Nanocrystals with Needle-Like Morphology for Effective Cancer Treatment
title_full PAMAM-Functionalized Cellulose Nanocrystals with Needle-Like Morphology for Effective Cancer Treatment
title_fullStr PAMAM-Functionalized Cellulose Nanocrystals with Needle-Like Morphology for Effective Cancer Treatment
title_full_unstemmed PAMAM-Functionalized Cellulose Nanocrystals with Needle-Like Morphology for Effective Cancer Treatment
title_short PAMAM-Functionalized Cellulose Nanocrystals with Needle-Like Morphology for Effective Cancer Treatment
title_sort pamam functionalized cellulose nanocrystals with needle like morphology for effective cancer treatment
topic cellulose nanocrystals
PAMAM dendrimer
cationic gene carrier
gene transfection
gene therapy
url https://www.mdpi.com/2079-4991/11/7/1640
work_keys_str_mv AT yanzhensun pamamfunctionalizedcellulosenanocrystalswithneedlelikemorphologyforeffectivecancertreatment
AT xiaolima pamamfunctionalizedcellulosenanocrystalswithneedlelikemorphologyforeffectivecancertreatment
AT xiaodongjing pamamfunctionalizedcellulosenanocrystalswithneedlelikemorphologyforeffectivecancertreatment
AT haohu pamamfunctionalizedcellulosenanocrystalswithneedlelikemorphologyforeffectivecancertreatment