'Click' synthesis of dextran macrostructures for combinatorial-designed self-assembled nanoparticles encapsulating diverse anticancer therapeutics.
'Click' synthesis of dextran macrostructures for combinatorial-designed self-assembled nanoparticles encapsulating diverse anticancer therapeutics.
复制标题
“点击”合成葡聚糖宏观结构，用于组合设计的封装多种抗癌疗法的自组装纳米颗粒。
DOI：
10.1016/j.bmc.2011.09.024
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发表时间：
2011-11-01
影响因子：
3.5
通讯作者：
Amiji, Mansoor M.
中科院分区：
文献类型：
--
作者：
Abeylath, Sampath C.;Amiji, Mansoor M.
关键词：
由于抗癌药物在全身给药时对健康组织的非特异性毒性，能够增强对肿瘤块和细胞的选择性的制剂是非常理想的。基于药物有效载荷的多样性，我们研究了一种组合设计策略，其中纳米制剂是根据药物的物理化学性质和给药需求定制的。以O-戊炔基右旋糖苷和相关叠氮化合物为原料，通过“点击”化学方法合成了脂类、硫醇类和聚乙二醇类分别功能化的C2~C12类葡聚糖衍生物。这些功能化的葡聚糖与抗癌药物结合后，在具有聚乙二醇表面功能化和分子间二硫键的水介质中自组装形成纳米颗粒。使用logP值为0.5~3.0的抗癌药物，初步评价了优化的纳米粒处方对−人卵巢腺癌细胞的细胞递送和细胞毒作用。结果表明，通过适当选择脂质修饰的葡聚糖，可以有效地为预期的治疗负载量身定制自组装纳米制剂。
With the non-specific toxicity of anticancer drugs to healthy tissues upon systemic administration, formulations capable of enhanced selectivity in delivery to the tumor mass and cells are highly desirable. Based on the diversity of the drug payloads, we have investigated a combinatorial-designed strategy where the nano-sized formulations are tailored based on the physicochemical properties of the drug and the delivery needs. Individually functionalized C2 to C12 lipid-, thiol-, and poly(ethylene glycol) (PEG)-modified dextran derivatives were synthesized via “click” chemistry from O-pentynyl dextran and relevant azides. These functionalized dextrans in combination with anticancer drugs form nanoparticles by self-assembling in aqueous medium having PEG surface functionalization and intermolecular disulfide bonds. Using anticancer drugs with logP values ranging from −0.5 to 3.0, the optimized nanoparticles formulations were evaluated for preliminary cellular delivery and cytotoxic effects in SKOV3 human ovarian adenocarcinoma cells. The results show that with the appropriate selection of lipid-modified dextran, one can effectively tailor the self-assembled nano-formulation for intended therapeutic payload.
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