Well-defined single polymer nanoparticles for the antibody-targeted delivery of chemotherapeutic agents.
Well-defined single polymer nanoparticles for the antibody-targeted delivery of chemotherapeutic agents.
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DOI：
10.1039/c4py01250j
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发表时间：
2015-02-28
影响因子：
4.6
通讯作者：
Convertine AJ
中科院分区：
文献类型：
--
作者：
Lane DD;Chiu DY;Su FY;Srinivasan S;Kern HB;Press OW;Stayton PS;Convertine AJ
采用水相可逆加成-断裂链转移（RAFT）聚合法制备了一系列N，N-二甲基丙烯酰胺（DMA）和2-羟乙基丙烯酰胺（HEAm）的线性共聚物，其分子量范围为3个数量级（103 ~ 106 Da），分子量范围为103 ~ 106 Da。使用DMAP催化的碳二亚胺化学将基于三硫代碳酸酯的RAFT链转移剂（CTA）接枝到这些支架上。所得的接枝链转移剂（gCTA）随后被用来合成聚合物刷与一些重要的乙烯基单体类，包括丙烯酰胺，甲基丙烯酰胺，和甲基丙烯酸酯。评价了来自10臂gCTA的DMA的水性RAFT聚合的刷聚合动力学。将含有羟基官能团的聚合物刷进一步官能化以制备第二代gCTA，其随后用于制备具有分子量超过106 Da的刷状结构的聚合物。这些所得的单颗粒纳米颗粒（SNP）通过DMA与受保护的肼基甲酸酯单体（bocSMA）的共聚用作蒽环类药物阿霉素的药物递送载体。还通过与生物素功能性单体（bioHEMA）共聚引入了细胞特异性靶向功能性。在SKOV 3卵巢癌细胞中评价了作为pH和血清的函数的腙连接的多柔比星的药物释放，并评价了化疗活性。
Aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization was employed to prepare a series of linear copolymers of N,N-dimethylacrylamide (DMA) and 2-hydroxyethylacrylamide (HEAm) with narrow Đ values over a molecular weight range spanning three orders of magnitude (103 to 106 Da). Trithiocarbonate-based RAFT chain transfer agents (CTAs) were grafted onto these scaffolds using carbodiimide chemistry catalyzed with DMAP. The resultant graft chain transfer agent (gCTA) was subsequently employed to synthesize polymeric brushes with a number of important vinyl monomer classes including acrylamido, methacrylamido, and methacrylate. Brush polymerization kinetics were evaluated for the aqueous RAFT polymerization of DMA from a 10 arm gCTA. Polymeric brushes containing hydroxyl functionality were further functionalized in order to prepare 2nd generation gCTAs which were subsequently employed to prepare polymers with a brushed-brush architecture with molecular weights in excess of 106 Da. These resultant single particle nanoparticles (SNPs) were employed as drug delivery vehicles for the anthracycline-based drug doxorubicin via copolymerization of DMA with a protected carbazate monomer (bocSMA). Cell-specific targeting functionality was also introduced via copolymerization with a biotin-functional monomer (bioHEMA). Drug release of the hydrazone linked doxorubicin was evaluated as function of pH and serum and chemotherapeutic activity was evaluated in SKOV3 ovarian cancer cells.