Xiaoli Sun

Shandong University, Jinan, Shandong Sheng, China

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Publications (5)17.35 Total impact

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    ABSTRACT: Low cytotoxicity and high transfection efficiency are critical issues in designing current non-viral gene delivery vectors. In the present study, a novel biomimetic lipid-polycation copolymer, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-graft-poly(l-lysine)-block-poly(ethylene glycol) (DOPE-g-PLL-b-PEG) was first synthesized and the potential of this novel hybrid lipid-polycation as efficient gene vector was further evaluated. DOPE-g-PLL-b-PEG and DNA could self-assemble into lipid modified polyion complex micelles (LPCM) through electrostatic interactions. Compared with PEG-b-PLL/DNA polyion complex micelles (PIC), LPCM could protect DNA from plasma, nuclease degradation in vitro and showed lower cytotoxicity to HepG2 and HeLa cells (P<0.05). The results of transfection study in vitro indicated that LPCM exhibited higher gene expression than PIC. Especially, the corresponding LPCM displayed the highest transfection efficiency in HeLa cells (P<0.05) when DOPE grafting ratio reached up to 30%. These results suggested that LPCM could facilitate gene transfer in cultured cells and might alleviate the drawbacks of the conventional cationic vector/DNA complexes. As a novel hybrid lipid-polycation, DOPE-g-PLL-b-PEG was valuable to be evaluated for its further application as gene carrier in vivo.
    International Journal of Pharmaceutics 04/2012; 425(1-2):62-72. · 3.99 Impact Factor
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    ABSTRACT: The success of gene therapy asks for the development of multifunctional vectors that could overcome various gene delivery barriers, such as the cell membrane, endosomal membrane, and nuclear membrane. Layer-by-layer technique is an efficient method with easy operation which can be used for the assembly of multifunctional gene carriers. This work describes a pH-sensitive multifunctional gene vector that offered long circulation property but avoided the inhibition of tumor cellular uptake of gene carriers associated with the use of polyethylene glycol. Deoxyribonucleic acid (DNA) was firstly condensed with protamine into a cationic core which was used as assembly template. Then, additional layers of anionic DNA, cationic liposomes, and o-carboxymethyl-chitosan (CMCS) were alternately adsorbed onto the template via layer-by-layer technique and finally the multifunctional vector called CMCS-cationic liposome-coated DNA/protamine/DNA complexes (CLDPD) was constructed. For in vitro test, the cytotoxicity and transfection investigation was carried out on HepG2 cell line. For in vivo evaluation, CMCS-CLDPD was intratumorally injected into tumor-bearing mice and the tumor cells were isolated for fluorescence determination of transfection efficiency. CMCS-CLDPD had ellipsoidal shapes and showed "core-shell" structure which showed stabilization property in serum and effective protection of DNA from nuclease degradation. In vitro and in vivo transfection results demonstrated that CMCS-CLDPD had pH-sensitivity and the outermost layer of CMCS fell off in the tumor tissue, which could not only protect CMCS- CLDPD from serum interaction but also enhance gene transfection efficiency. These results demonstrated that multifunctional CMCS-CLDPD had pH- sensitivity, which may provide a new approach for the antitumor gene delivery.
    International Journal of Nanomedicine 01/2012; 7:925-39. · 4.20 Impact Factor
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    ABSTRACT: The clinical success of gene therapy for lung cancer is not only dependent on efficient gene carriers but also on a suitable delivery route. A pulmonary delivery route can directly deliver gene vectors to the lung which is more efficient than a systemic delivery route. For gene carriers, cationic liposomes have recently emerged as leading non-viral vectors in worldwide gene therapy clinical trials. However, cytotoxic effects or apoptosis are often observed which is mostly dependent on the cationic lipid used. Therefore, an efficient and safe cationic lipid, 6-lauroxyhexyl lysinate (LHLN), previously synthesized by our group was first used to prepare cationic liposomes. Physicochemical and biological properties of LHLN-liposomes were investigated. LHLN-liposome/DNA complexes showed positive surface charge, spherical morphology, a relatively narrow particle size distribution and strong DNA binding capability. Compared with Lipofectamine2000, the new cationic liposome formulation using LHLN exhibited not only lower cytotoxicity (P < 0.05) but also similar transfection efficiency in A549 and HepG2 lung cancer cells for in vitro tests. When administered by intratracheal instillation into rat lungs for in vivo evaluation, LHLN-liposome/DNA complexes exhibited higher pulmonary gene transfection efficiency than Lipofectamine2000/DNA complexes (P < 0.05). These results suggested that LHLN-liposomes may have great potential for efficient pulmonary gene delivery.
    Nanotechnology 06/2011; 22(24):245104. · 3.84 Impact Factor
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    ABSTRACT: Low cytotoxicity and high gene transfection efficiency are critical issues in designing current non-viral gene delivery vectors. The purpose of the present work was to synthesize the novel biodegradable poly (lactic acid)-poly(ethylene glycol)-poly(l-lysine) (PLA-PEG-PLL) copolymer, and explore its applicability and feasibility as a non-viral vector for gene transport. PLA-PEG-PLL was obtained by the ring-opening polymerization of Lys(Z)-NCA onto amine-terminated NH(2)-PEG-PLA, then acidolysis to remove benzyloxycarbonyl. The tri-block copolymer PLA-PEG-PLL combined the characters of cationic polymer PLL, PLA and PEG: the self-assembled nanoparticles (NPs) possessed a PEG loop structure to increase the stability, hydrophobic PLA segments as the core, and the primary ɛ-amine groups of lysine in PLL to electrostatically interact with negatively charged phosphate groups of DNA to deposit with the PLA core. The physicochemical properties (morphology, particle size and surface charge) and the biological properties (protection from nuclease degradation, plasma stability, in vitro cytotoxicity, and in vitro transfection ability in HeLa and HepG2 cells) of the gene-loaded PLA-PEG-PLL nanoparticles (PLA-PEG-PLL NPs) were evaluated, respectively. Agarose gel electrophoresis assay confirmed that the PLA-PEG-PLL NPs could condense DNA thoroughly and protect DNA from nuclease degradation. Initial experiments showed that PLA-PEG-PLL NPs/DNA complexes exhibited almost no toxicity and higher gene expression (up to 21.64% in HepG2 cells and 31.63% in HeLa cells) than PEI/DNA complexes (14.01% and 24.22%). These results revealed that the biodegradable tri-block copolymer PLA-PEG-PLL might be a very attractive candidate as a non-viral vector and might alleviate the drawbacks of the conventional cationic vectors/DNA complexes for gene delivery in vivo.
    International Journal of Molecular Sciences 01/2011; 12(2):1371-88. · 2.46 Impact Factor
  • Xiaoli Sun, Na Zhang
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    ABSTRACT: The polyplexes which are formed between cationic polymers and DNA through electrostatic interactions and thus known as polycation/DNA complexes, are by far the most widely used non-viral gene delivery vectors. Many factors such as molecular weight, surface charge, charge density, hydrophilicity and the structure of cationic polymers affect gene transfection efficiency of cationic polymers. Therefore, optimization of cationic polymers is necessary to improve the gene transfection efficiency. Currently several important cationic polymers were used as cationic vectors for gene delivery which included PEI, PLL, Chitosan and PAMAM. Their most advantages and the rational design are introduced in this article. However, these systems are much less efficient in gene transfer experiments compared with viral systems. Some strategies such as PEGylation, combination and multifunctional modification were developed in the cationic polymeric vectors for gene delivery. Hereby, this article will review various kinds of copolymers with higher stability but biodegradable, bioresponsive and easy refined molecular weight which could be easily modification. Especially, the multifunctional modified polyplexes and polymersomes will be further discussion due to their ability to conjugate biologically active ligands, which can be used as potential nanostructured biomaterials for future in vivo gene delivery.
    Mini Reviews in Medicinal Chemistry 02/2010; 10(2):108-25. · 2.87 Impact Factor