Synthesis, characterization, and gene delivery of Poly-L-lySine octa(3-aminopropyl)silsesquioxane dendrimers: nanoglobular drug carriers with precisely defined molecular Architectures
Synthesis, characterization, and gene delivery of Poly-L-lySine octa(3-aminopropyl)silsesquioxane dendrimers: nanoglobular drug carriers with precisely defined molecular Architectures
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DOI：
10.1021/mp070036z
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发表时间：
2007-09-01
影响因子：
4.9
通讯作者：
Lu, Zheng-Rong
中科院分区：
文献类型：
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作者：
Kaneshiro, Todd L.;Wang, Xuli;Lu, Zheng-Rong
具有确定的纳米尺寸的大分子-纳米颗粒-被合成并表征为具有精确分子结构的新型药物载体。具有立方八面体的聚L-赖氨酸树枝状大分子（3-氨基丙基）倍半硅氧烷（OAS）核，（L-赖氨酸）（8）-OAS，（L-赖氨酸）16（L-赖氨酸）（8）-OAS，（L-赖氨酸）（32）-（L-赖氨酸）（16）-（L-赖氨酸）（8）-OAS，和（L-赖氨酸）（64）-（L-赖氨酸）（32）-（L-赖氨酸）（16）-（L-赖氨酸）（8）-OAS的液相肽化学合成，产率高，纯度好。基质辅助激光解吸飞行时间（MALDI-TOF）质谱显示在合成过程中低代树枝状聚合物的表面氨基完全取代，以及精确定义的分子结构。纳米粒子通过H-1-和C-13-NMR和2D-NMR（相关光谱（COSY）和脉冲场梯度异质多量子相关（gHMQC））光谱进一步表征纳米粒子的结构。1H-1-NMR光谱表明，纳米粒子具有相对刚性的分子结构。细胞毒性研究表明，这些纳米粒子表现出尺寸依赖性的毒性，但它远低于线性聚-L-赖氨酸。初步的体外核酸递送研究表明，这些球状树枝状聚合物可以有效地将质粒DNA递送至MDA-MB-231细胞。这些纳米粒子作为具有精确定义的分子结构的安全药物载体具有很大的希望。
Macromolecules with defined nanosizes-nanoglobules-were synthesized and characterized as novel drug carriers with precise molecular architectures. Poly-L-lysine dendrimers with a cubic octa(3-aminopropyl)silsesquioxane (OAS) core, (L-lysine)(8)-OAS, (L-lysine)16(L-lysine)(8)-OAS, (L-lysine)(32)-(L-lysine)(16)-(L-lysine)(8)-OAS, and (L-lysine)(64)-(L-lysine)(32)-(L-lysine)(16)(L-lysine)(8)-OAS, were divergently synthesized by solution phase peptide chemistry in good yield and purity. Matrix-assisted laser desorption time of flight (MALDI-TOF) mass spectrometry showed complete substitution of the surface amino groups of lower generation dendrimers during synthesis, as well as precisely defined molecular architectures of. the nanoglobules. The structures of the nanoglobules were further characterized by H-1- and C-13-NMR and 2D-NMR (correlation spectroscopy (COSY) and pulsed-field-gradient heteronuclear multiple quantum correlation (gHMQC)) spectroscopy. The H-1-NMR spectroscopy revealed that the nanoglobules had a relatively rigid molecular architecture. Cytotoxicity studies showed that these nanoglobules exhibited a size-dependent toxicity, but it was much lower than that of linear poly-L-lysine. Preliminary in vitro nucleic acid delivery studies have shown that these globular dendrimers; can efficiently deliver plasmid DNA to MDA-MB-231 cells. These nanoglobules hold much promise as safe drug carriers with precisely defined molecular architecture.