ABSTRACT
ABSTRACT Cationic polymers such as polyallylamine (PAA) having primary amino groups are poor transfection agents and possess a high cytotoxicity index when used without any chemical modification. In this study, PAA was modified with cholesterol in order to improve transfection efficiency and to reduce cytotoxicity. PAA polymers with molecular weights of 15 and 65 kDa were selected and grafted with cholesterol at percentages of 5, 10, 15, 30, and 50. After purification, the efficacy of the synthetic vectors was evaluated in terms of DNA condensation using the ethidium bromide test, buffering capacity, particle size, zeta potential, transfection efficiency, and cytotoxicity assay in Neuro2A cell lines. According to the ethidium bromide test, these vectors can condense DNA at moderate and high carrier to plasmid (C/P) ratios. The buffering capacity of the prepared vector in both molecular weights was less than unmodified PAA. Particle size measurements demonstrated that modified PAAs were able to form nanoparticles ranging in size from 125 to 530 nm. The vectors based on PAA 15 kDa demonstrated a better transfection efficiency than the vectors made of PAA 65 kDa. Cytotoxicity studies showed that toxicity of all vectors was less than PAA. Some cholesterol modified polymers composed of PAA (15 kDa) were suitable vectors for gene delivery with low cytotoxicity.
Subject(s)
Genetic Therapy , Cholesterol/therapeutic use , Polymers , Transfection/instrumentationABSTRACT
RNA interference (RNAi) is a method that allows double-stranded RNA (dsRNA) to induce the target gene mRNA to degrade in the body and lead to different levels of gene silencing. Small interfering RNA (siRNA) is the effector molecules of RNAi, and needs the delivery vehicle into the cells to play a therapeutic role. Nanoscale carrier can adjust the rate of drug release, increase permeability of biofilm, change distribution in the body, and improve bioavailability. In this manuscript, materials, structure and biological characteristics of existing non-viral nanometer vectors delivery for siRNA are summarized.
ABSTRACT
RNA interference(RNAi)is a method that allows double-stranded RNA(dsRNA)to induce the target gene mRNA to degrade in the body and lead to different levels of gene silencing. Small interfering RNA(siRNA)is the effector molecules of RNAi, and needs the delivery vehicle into the cells to play a therapeutic role. Nanoscale carrier can adjust the rate of drug release ,increase permeability of biofilm,change distribution in the body,and improve bioavailability. In this manuscript,materials,structure and bio?logical characteristics of existing non-viral nanometer vectors delivery for siRNA are summarized.
ABSTRACT
The current therapies for treating prostate cancer, in many cases, also cause damage to normal tissues and organs at the same time when killing cancer cells. The recent development of targeted therapy to some extent, may be a good solution to this problem. As vectors in targeted therapy, viral vectors have strong immunogenicity, toxicity and other disadvantages, and non-viral vectors for targeted therapy of prostate cancer may overcome these drawbacks. This review summarized the recent application of cationic polymers, liposomes and polymeric chitosan as non-viral vectors of gene drug for targeted therapy of prostate cancer.