Thiolated Chitosan/DNA Nanocomplexes Exhibit Enhanced and Sustained Gene Delivery

Lee, Dongwon; Zhang, Weidong; Shirley, Shawna A.; Kong, Xiaoyuan; Hellermann, Gary; Lockey, Richard F.; Mohapatra, Shyam S.

doi:10.1007/s11095-006-9136-9

Cited by 155 publications

(61 citation statements)

References 44 publications

(48 reference statements)

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“…Thiolated chitosan under optimum conditions physically condenses nucleic acids. 30 This contributes to the formation of nanoparticles (200 ± 30 nm), with an acceptable level of cellular uptake demonstrated by downregulation of EGFR expression in T47D cells.…”

Section: Resultsmentioning

confidence: 99%

“…The size range of these particles is comparable to the particle sizes obtained by other groups. 26 Cell toxicity assay conducted according to MTS where active substances and formulated nanoparticles were used demonstrated that DOX in any form (free/nanoparticle) applied to cells was toxic and significantly decreased cell survival in comparison with both controls (RPMI + 10% FBS and FBS-free RPMI) and other treatments (Figure 4). Thus the cells were not resistant to this compound.…”

Section: Preparation Of Nanoparticles and Nanoparticle Characterizationmentioning

confidence: 99%

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Thiolated chitosan nanoparticles as a delivery system for antisense therapy: evaluation against EGFR in T47D breast cancer cells

Talaei

Azizi²,

Dinarvand³

et al. 2011

IJN

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Thiolated chitosan has high transfection and mucoadhesive properties. We investigated the potential of two recently synthesized polymers: NAC-C (N-acetyl cysteine-chitosan) and NAP-C (N-acetyl penicillamine-chitosan) in anticancer drug delivery targeting epidermal growth factor receptor (EGFR). Doxorubicin (DOX) and antisense oligonucleotide (ASOND)-loaded polymer nanoparticles were prepared in water by a gelation process. Particle characterization, drug loading, and drug release were evaluated. To verify drug delivery efficiency in vitro experiments on a breast cancer cell line (T47D) were performed. EGFR gene and protein expression was analyzed by real time quantitative polymerase chain reaction and Western blotting, respectively. A loading percentage of 63% ± 5% for ASOND and 70% ± 5% for DOX was achieved. Drug release data after 15 hours showed that ASOND and DOX were completely released from chitosan-based particles while a lower and more sustained release of only 22% ± 8% was measured for thiolated particles. In a cytosol simulated release medium/reducing environment, such as found intracellularly, polymer-based nanoparticles dissociated, liberating approximately 50% of both active substances within 7 hours. ASOND-loaded polymer nanoparticles had higher stability and high mucoadhesive properties. The ASOND-loaded thiolated particles significantly suppressed EGFR gene expression in T47D cells compared with ASOND-loaded chitosan particles and downregulated EGFR protein expression in cells. This study could facilitate future investigations into the functionality of NAP-C and NAC-C polymers as an efficient ASOND delivery system in vitro and in vivo.

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Section: Resultsmentioning

confidence: 99%

Section: Preparation Of Nanoparticles and Nanoparticle Characterizationmentioning

confidence: 99%

Thiolated chitosan nanoparticles as a delivery system for antisense therapy: evaluation against EGFR in T47D breast cancer cells

Talaei

Azizi²,

Dinarvand³

et al. 2011

IJN

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“…It is imperative that siRNA reach the cytoplasm of the target cell to become effective and induce silencing. A major limitation in the therapeutic use of siRNA is its rapid degradation in the plasma and cellular cytoplasm, resulting in a short half-life [36][37][38]. Furthermore, naked siRNA cannot passively diffuse through cellular membranes due to the strong anionic charge of the phosphate backbone and consequent electrostatic repulsion from the anionic cell membrane surface.…”

Section: Discussionmentioning

confidence: 99%

A nanoformulation of siRNA and its role in cancer therapy: In vitro and in vivo evaluation

Jagani

Rao

Palanimuthu³

et al. 2013

Cellular and Molecular Biology Letters

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Overexpression of anti-apoptotic Bcl-2 is often observed in a wide variety of human cancers. It prevents the induction of apoptosis in neoplastic cells and contributes to resistance to chemotherapy. RNA interference has emerged as an efficient and selective technique for gene silencing. The potential to use small interfering RNA (siRNA) as a therapeutic agent for the treatment of cancer has elicited a great deal of interest. However, insufficient cellular uptake and poor stability have limited its therapeutic applications. The purpose of this study was to prepare chitosan nanoparticles via ionic gelation of chitosan by tripolyphosphate for effective delivery of siRNA to silence the anti-apoptotic Bcl-2 gene in neoplastic cells. Chitosan nanoparticles loaded with siRNA were in the size range 190 to 340 nm with a polydispersive index ranging from 0.04 to 0.2. They were able to completely bind with siRNA, provide protection against nuclease degradation, and enhance the transfection. Cell culture studies revealed that nanoparticles with entrapped siRNA could efficiently silence the antiapoptotic Bcl-2 gene. Studies on Swiss albino mice showed that siRNA could be effectively delivered through nanoparticles. There was significant decrease in the tumor volume. Blocking the expression of anti-apoptotic Bcl-2 can enhance

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“…Chitosan is biodegradable, biocompatible, low immunogenicity and non-toxic at low molecular weights (10-50 kDa). It has been suggested that the toxicity of chitosan is perhaps due to impurities in the chitosan polymers [49][50][51][52][53][54][55][56][57][58][59][60].…”

Section: Chitosanmentioning

confidence: 99%

Biopolymer in Gene Delivery

Prabu¹,

Kandasamy²

2017

Advanced Technology for Delivering Therapeutics

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Nowadays, biopolymers, a class of biomaterials, represent frontier area in the drug delivery systems. Drug release from nano-and microparticles is a complex process, which involves several steps. Uptake of nanoparticle in the intracellular is affected by numerous factors. Recently, gene delivery has been considered one of the promising approaches for the treatment of various diseases acquired genetically in human being. The use of biopolymers as nanoparticles in gene delivery can potentially avoid many of the safety concerns in the gene delivery system. In gene delivery, the genetic materials such as DNA plasmids, RNA and siRNA are either encapsulated inside or conjugated to the nanoparticles, which protects the genetic materials until the drug reaches its target site. Treatment of the diseases is based on the effective delivery of the genetic materials into specific cells that are responsible for disease development. Various properties such as particle size, surface charge, morphology of the surface and release rate of the loaded molecules are the important parameters in the gene delivery system. In this chapter, various biopolymers (cationic polymers) and inorganic non-viral-delivery vectors used in gene delivery used as therapeutic agents are discussed.

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Thiolated Chitosan/DNA Nanocomplexes Exhibit Enhanced and Sustained Gene Delivery

Abstract: Thiolated chitosans condense pDNA to form nanocomplexes, which exhibit a significantly higher gene transfer potential and sustained gene expression upon crosslinking, indicating their great potential for gene therapy and tissue engineering.

Cited by 155 publications

References 44 publications

Thiolated chitosan nanoparticles as a delivery system for antisense therapy: evaluation against EGFR in T47D breast cancer cells

Thiolated chitosan nanoparticles as a delivery system for antisense therapy: evaluation against EGFR in T47D breast cancer cells

A nanoformulation of siRNA and its role in cancer therapy: In vitro and in vivo evaluation

Biopolymer in Gene Delivery

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