Folate Receptor-Mediated Cancer Cell Specific Gene Delivery Using Folic Acid-Conjugated Oligochitosans

2006 ◽  
Vol 6 (9) ◽  
pp. 2860-2866 ◽  
Author(s):  
Dongwon Lee ◽  
Richard Lockey ◽  
Shyam Mohapatra
Keyword(s):  
Folic Acid ◽  
Gene Transfer ◽  
Gene Delivery ◽  
Cancer Cells ◽  
Transfection Efficiency ◽  
Folate Receptor ◽  
Weight Ratio ◽  
Specific Gene ◽  
Transfer Potential

Chitosan-mediated gene delivery has gained an increasing interest due to its ability to treat cancers and genetic diseases. However, low transfection efficiency and lack of target specificity limit its application for gene and drug delivery. In the present work, folic acid was covalently conjugated to chitosan as a targeting ligand in an attempt to specifically deliver DNA to folate receptor-overexpressing cancer cells. Folic acid-conjugated chitosan (FACN) was successfully synthesized and characterized by 1H-NMR and is biocompatible. In vitro gene transfer potential of FACN was evaluated in human epithelial ovarian cancer OV2008 cells and human breast cancer MCF-7 cells. FACN at a weight ratio of 10 : 1 exhibited significantly (< 0.01) enhanced gene transfer potential in folate receptor-overexpressing cancer cells as compared to unmodified chitosan. Transfection of FACN/pDNA nanocomplexes is competitively inhibited by free folic acid, suggesting the specific gene delivery of FACN/pDNA nanocomplexes is achieved through folate receptor-mediated endocytosis. Taken together, these results demonstrate that FACN provides a promising carrier for cancer gene therapy.

scholarly journals Optimisation of Folate-Mediated Liposomal Encapsulated Arsenic Trioxide for Treating HPV-Positive Cervical Cancer Cells In Vitro

2019 ◽  
Vol 20 (9) ◽  
pp. 2156 ◽  
Author(s):  
Akhtar ◽  
Ghali ◽  
Wang ◽  
Bell ◽  
Li ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Folic Acid ◽  
Cancer Cells ◽  
Arsenic Trioxide ◽  
Folate Receptor ◽  
Hpv Infection ◽  
Cytotoxicity Studies ◽  
Cervical Cancer Cells ◽  
Infected Cells

High-risk human papilloma virus (HPV) infection is directly associated with cervical cancer development. Arsenic trioxide (ATO), despite inducing apoptosis in HPV-infected cervical cancer cells in vitro, has been compromised by toxicity and poor pharmacokinetics in clinical trials. Therefore, to improve ATO’s therapeutic profile for HPV-related cancers, this study aims to explore the effects of length of ligand spacers of folate-targeted liposomes on the efficiency of ATO delivery to HPV-infected cells. Fluorescent ATO encapsulated liposomes with folic acid (FA) conjugated to two different PEG lengths (2000 Da and 5000 Da) were synthesised, and their cellular uptake was examined for HPV-positive HeLa and KB and HPV-negative HT-3 cells using confocal microscopy, flow cytometry, and spectrophotometer readings. Cellular arsenic quantification and anti-tumour efficacy was evaluated through inductively coupled plasma-mass spectrometry (ICP-MS) and cytotoxicity studies, respectively. Results showed that liposomes with a longer folic acid-polyethylene glycol (FA-PEG) spacer (5000 Da) displayed a higher efficiency in targeting folate receptor (FR) + HPV-infected cells without increasing any inherent cytotoxicity. Targeted liposomally delivered ATO also displayed superior selectivity and efficiency in inducing higher cell apoptosis in HPV-positive cells per unit of arsenic taken up than free ATO, in contrast to HT-3. These findings may hold promise in improving the management of HPV-associated cancers.

scholarly journals In Vitro Gene Delivery Mediated by Asialofetuin-Appended Cationic Liposomes Associated with γ-Cyclodextrin into Hepatocytes

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Keiichi Motoyama ◽  
Yoshihiro Nakashima ◽  
Yukihiko Aramaki ◽  
Fumitoshi Hirayama ◽  
Kaneto Uekama ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Gene Delivery ◽  
Plasmid Dna ◽  
Transfection Efficiency ◽  
Cationic Liposomes ◽  
Nonviral Vector ◽  
Liposomal Membrane ◽  
Transfer Activity ◽  
Potential Use

The purpose of this study is to evaluate in vitro gene delivery mediated by asialofetuin-appended cationic liposomes (AF-liposomes) associating cyclodextrins (CyD/AF-liposomes) as a hepatocyte-selective nonviral vector. Of various CyDs, AF-liposomes associated with plasmid DNA (pDNA) and γ-cyclodextrin (γ-CyD) (pDNA/γ-CyD/AF-liposomes) showed the highest gene transfer activity in HepG2 cells without any significant cytotoxicity. In addition, γ-CyD enhanced the encapsulation ratio of pDNA with AF-liposomes, and also increased gene transfer activity as the entrapment ratio of pDNA into AF-liposomes was increased. γ-CyD stabilized the liposomal membrane of AF-liposomes and inhibited the release of calcein from AF-liposomes. The stabilizing effect of γ-CyD may be, at least in part, involved in the enhancing gene transfer activity of pDNA/γ-CyD/AF-liposomes. Therefore, these results suggest the potential use of γ-CyD for an enhancer of transfection efficiency of AF-liposomes.

Functional Amphiphiles for Gene Delivery

MRS Bulletin ◽  
2005 ◽  
Vol 30 (9) ◽  
pp. 647-653 ◽  
Author(s):  
Philippe Barthélémy ◽  
Michel Camplo
Keyword(s):  
Gene Transfer ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Research Activity ◽  
Safety Issues ◽  
Significant Research

AbstractThe design of safe and efficient gene transfer vectors remains one of the key challenges in gene therapy. Despite their remarkable transfection efficiency, viral vectors suffer from known safety issues. Consequently, significant research activity has been undertaken to develop nonviral approaches to gene transfer during the last decade. Numerous academic and industrial research groups are investigating synthetic cationic vectors, such as cationic amphiphiles, with the objective of increasing the gene transfection activity. Within this area, the development of functional synthetic vectors that respond to local environmental effects have met with success. These synthetic vectors are based on mechanistic principles and represent a significant departure from earlier systems. Many of these systems for gene delivery in vitro and in vivo are discussed in this article.

The Effect of Spermidine and Spermine on Chitosan-Mediated Gene Delivery

2020 ◽  
Vol 859 ◽  
pp. 113-119
Author(s):  
Auayporn Apirakaramwong ◽  
Songporn Sunthornphan ◽  
Nutcha Pasuthawong ◽  
Tanawin Intaravicha ◽  
Nattapon Ruangthai ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Viral Vector ◽  
Transfection Efficiency ◽  
Weight Ratio ◽  
Green Fluorescence Protein ◽  
Ternary Complexes ◽  
Average Cell ◽  
Living Organisms ◽  
Almost All

Chitosan (CS) is a biodegradable and highly positive charged polymer that can be utilized as a non-viral vector for gene delivery. However, its transfection efficiency is low. Spermidine (SPD) and spermine (SPM) are ordinary polyamines found in almost all living organisms. Their structures contain tri- and tetra-amine, respectively. The present study aims to elucidate the effect of SPD or SPM on transfection efficiency and cytotoxicity of CS/DNA complexes in human cervical carcinoma (HeLa) cells. The ternary complexes (CS, DNA and SPD or SPM) at different weight ratios and mixing orders were formulated and tested on transfection efficiency. Their particle sizes and charges were also estimated. CS that has a molecular weight of 45,000 Daltons and degree of deacetylation of 85 was able to form complete complex with plasmid DNA expressing enhanced green fluorescence protein (pEGFP-C2) at weight ratio of 4. The SPM/CS/DNA (1:4:1) and SPD/ CS/DNA (512:4:1) complexes illustrated the greatest transfection efficiency. Moreover, the transfection efficiency was affected by the mixing order between CS, DNA and SPD or SPM. For cell toxicity experiments, more than 85% the average cell survival of the complexes were detected by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) cell growth assay. These findings suggest that addition of either SPD or SPM to CS before forming ternary complexes with DNA may significantly improve gene delivery potential in vitro.

scholarly journals Histidine-Tagged Folate-Targeted Gold Nanoparticles for Enhanced Transgene Expression in Breast Cancer Cells In Vitro

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 53
Author(s):  
Calrin Joseph ◽  
Aliscia Daniels ◽  
Sooboo Singh ◽  
Moganavelli Singh
Keyword(s):  
Breast Cancer ◽  
Gold Nanoparticles ◽  
Gene Delivery ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Folate Receptor ◽  
Endosomal Escape ◽  
Delivery Vehicles ◽  
Gene Delivery Vehicles

Nanotechnology has emerged as a promising treatment strategy in gene therapy, especially against diseases such as cancer. Gold nanoparticles (AuNPs) are regarded as favorable gene delivery vehicles due to their low toxicity, ease of synthesis and ability to be functionalized. This study aimed to prepare functionalized AuNPs (FAuNPs) and evaluate their folate-targeted and nontargeted pCMV-Luc-DNA delivery in breast cancer cells in vitro. CS was added to induce stability and positive charges to the AuNPs (Au-CS), histidine (Au-CS-His) to enhance endosomal escape and folic acid for folate-receptor targeting (Au-CS-FA-His). The FAuNP:pDNA nanocomplexes possessed favorable sizes (<135 nm) and zeta potentials (<−20 mV), strong compaction efficiency and were capable of pDNA protection against nuclease degradation. These nanocomplexes showed minimal cytotoxicity (>73% cell viability) and enhanced transgene activity. The influence of His was notable in the HER2 overexpressing SKBR3 cells, which produced higher gene expression. Furthermore, the FA-targeted nanocomplexes enhanced receptor-mediated endocytosis, especially in MCF-7 cells, as confirmed by the receptor competition assay. While the role of His may need further optimization, the results achieved suggest that these FAuNPs may be suitable gene delivery vehicles for breast cancer therapeutics.

Hepatocyte-Specific Gene Delivery with Galactose-Bearing Cationic Polymers with Different Molecular Structures

2012 ◽  
Vol 86 ◽  
pp. 86-91 ◽  
Author(s):  
Maria Chiara Munisso ◽  
Atsushi Mahara ◽  
Yoichi Tachibana ◽  
Jeong Hun Kang ◽  
Satoshi Obika ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Viral Vector ◽  
Transfection Efficiency ◽  
Molecular Structures ◽  
Specific Gene ◽  
Cationic Polymers ◽  
Gene Therapies ◽  
Polymeric Carriers ◽  
Significant Efficacy

Since the promising virus -based gene therapies are often limited by problems such as the immunity of virus itself, the development of an efficient non-viral vector is of prime importance. For this reason, several synthetic nonviral polymeric carriers including cationic sequences have been molecularly designed. It is well known that the polymeric carriers with some cationic groups buffer the endosomal pH resulting in the enhanced transfection efficiency, but also in a relatively high toxicity. In the last decades, the polymers bearing pendant carbohydrates (glycopolymers) was proved to have relatively less toxic. Since the glycopolymers may not only decrease the toxicity of the cationic chain but also serve as targeting agent, we have rationally designed new glycopolymer-based gene delivery carriers. The interaction of carrier/gene polyplexes with hepatocytes and their intracellular trafficking were investigated in vitro. Our results show the significant efficacy of the galactose moieties on the uptake by hepatocytes, in a ligand specific manner.

scholarly journals Light-induced adenovirus gene transfer, an efficient and specific gene delivery technology for cancer gene therapy

2002 ◽  
Vol 9 (4) ◽  
pp. 365-371 ◽  
Author(s):  
Anders Høgset ◽  
Birgit Øvstebø Engesæter ◽  
Lina Prasmickaite ◽  
Kristian Berg ◽  
Øystein Fodstad ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Gene Delivery ◽  
Cancer Gene Therapy ◽  
Specific Gene ◽  
Cancer Gene ◽  
Delivery Technology

Folic acid-conjugated green luminescent carbon dots as a nanoprobe for identifying folate receptor-positive cancer cells

Talanta ◽  
2018 ◽  
Vol 183 ◽  
pp. 39-47 ◽  
Author(s):  
Junli Zhang ◽  
Xuewei Zhao ◽  
Ming Xian ◽  
Chuan Dong ◽  
Shaomin Shuang
Keyword(s):  
Folic Acid ◽  
Cancer Cells ◽  
Carbon Dots ◽  
Folate Receptor
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