Complexes containing cationic and anionic pH-sensitive liposomes: comparative study of factors influencing plasmid DNA gene delivery to tumors

Abstract

pH-sensitive liposomes represent an effective gene vector in cancer therapy. However, their use is greatly hampered by their relatively low transfection efficiency. To improve the transfection efficiency of pH-sensitive liposomes, we prepared complexes containing 3β-[N-(N′,N′-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) and dioleoylphosphatidyl ethanolamine (DOPE) liposomes and pH-sensitive liposomes composed of cholesteryl hemisuccinate (CHEMS) and DOPE, and evaluated the influence of various factors on plasmid DNA (pDNA) transfection efficiency. All DC-Chol/DOPE liposome/pDNA and pH-sensitive liposome complexes showed similarly potent pH sensitivity. In the presence of serum-containing medium, two optimized complexes of DC-Chol/DOPE liposomes/pDNA and pH-sensitive PEGylated liposomes showed high transfection efficiency of 22.94% and 20.07%, respectively. Notably, DC-Chol/DOPE (2:3) liposomes/pH-sensitive PEGylated (1%) liposome complexes with a charge ratio of 1:1 (m/m [+/−]) showed enhanced accumulation in tumors in vivo. Our results show the influence of various factors on pDNA transfection efficiency in complexes of DC-Chol/DOPE liposomes and pH-sensitive PEGylated liposomes. Understanding of such mechanisms will lead to better design of complexes of DC-Chol/DOPE liposomes and pH-sensitive liposomes for gene therapy.

Using hyaluronic acid-functionalized pH stimuli-responsive mesoporous silica nanoparticles for targeted delivery to CD44-overexpressing cancer cells

“…[14][15][16][17] The pH-sensitive lipid membrane that target tumors are stable at physiological pH values, but are designed to become unstable under acidic conditions, resulting in the release of their drug cargo. 18 Some studies have shown that coated nanoparticles of pH-sensitive lipid membrane can protect the drug and increase the drug concentration, which is favored to decrease systemic toxicity and enhance antitumor activity. 14,15 Hyaluronic acid (HA) is a kind of functional material that acts as a drug carrier or targeting moiety, which is a natural ligand for cancer cells overexpressing CD44 and that could interact with a CD44 receptor excessively expressed in most tumor cells.…”

Gene Therapy for Pyoderma Gangrenosum: Optimal Transfection Conditions and Effect of Drugs on Gene Delivery in the HaCaT Cell Line Using Cationic Liposomes

“…Local pH alters the state of protonation in the transfection system and has an important bearing on transfection efficiency. The sensitivity of liposomes to pH may additionally be taken advantage of in certain situations, by designing pH-sensitive liposomes and other nanoparticles that are stable at physiological pH but become unstable at lower pH such as those found in diseased tissue, releasing the DNA or drug they are carrying [40,41]. This study has found the optimum pH for transfection of the HaCaT cell line, under the conditions used, to be pH 7.…”

Current State of the Art in DNA Vaccine Delivery and Molecular Adjuvants: Bcl-xL Anti-Apoptotic Protein as a Molecular Adjuvant

“…Neutral lipids (DOPE, DPPC, DOPC and Chol) are also often involved in the cationic liposome structure for more efficient transport systems, although sometimes only cationic lipids (DOTAP, DC-Chol, MMRIE, DODAP, DDTAP and DDA) are used [8,36,53]. The choice of ideal colipids is important during the formulation phase [54][55][56], since they significantly affect the overall performance of cationic liposomes.…”

“…Various studies have shown that cationic liposomes (DC-Chol/DOPE) formed at various ratios of 3β-[N-(N′,N′-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) and 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE) are effective pDNA carriers in the preclinical as well clinical trials for plasmid transfection [55,57,60]. In another study, it was reported that the vaccine adjuvants with high immunogenicity were obtained with cationic liposomes formed at 50:50 ratio (50 mol%) with DC-Chol/DPPC (3β-[N-(N′,N′-dimethylaminoethane) carbamoyl] cholesterol/1,2-dipalmitoyl-sn-glycero-3-phosphocholine) [53].…”