Molecular Self-Assembly of a Homopolymer: An Alternative To Fabricate Drug-Delivery Platforms for Cancer Therapy
Molecular Self-Assembly of a Homopolymer: An Alternative To Fabricate Drug-Delivery Platforms for Cancer Therapy
复制标题
均聚物的分子自组装：制造癌症治疗药物输送平台的替代方案
DOI：
10.1002/anie.201102280
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发表时间：
2011-01-01
影响因子：
16.6
通讯作者：
Yan, Deyue
中科院分区：
文献类型：
--
作者：
Liu, Jinyao;Huang, Wei;Yan, Deyue
合成聚合物在选择性溶剂中或通过层层组装的方法进行分子自组装引起了人们极大的兴趣。[1，2]大多数报道的用于在选择性溶剂中自组装的前体是两亲性线性/树枝状嵌段共聚物。[3，4]最近，共价嵌段前体已扩展到超分子前体。[5]然而，很少有人关注的分子自组装的均聚物衍生自一种类型的单体。有没有一种均聚物可以在非共价相互作用的驱动下自发地聚集成高度有序的结构？为了回答这个问题，我们合成了一种新型的两亲性均聚物，并实现了其水溶液自组装，形成了具有非常窄的粒径分布的球形胶束。所得胶束表现出智能氧化还原响应特性，可用于快速将疏水性药物递送到肿瘤细胞核中并增强对细胞增殖的抑制。所用单体为2-[（2-羟乙基）-二硫烷基]乙氧基-2-氧代-1，3，2-二氧磷杂环戊烷，由疏水和亲水部分组成，可以通过自缩合开环聚合（SCROP）聚合成超支化聚磷酸盐（HPHDP）。[6]HPHDP是一种两亲性均聚物，沿着高度支化的结构具有交替的疏水性二硫化物和亲水性多磷酸盐链段沿着（方案1）。合成了三种不同分子量的HPHDP样品。不同前体样品和相应胶束的表征数据总结于表1中。[7]通常，超支化聚合物的分子量分布非常宽。然而，通过透析除去产物中的低分子量物质，因此最终样品的Mw/Mn值等于或小于1.72。通过NMR光谱法测量的支化度（DB）接近0.5。图1a显示了HPHDP胶束的典型透射电子显微镜（TEM）图像，图1b是仅一个胶束的放大TEM图像。有趣的是，胶束是相当均匀的。基于每个HPHDP样品的100个胶束的统计分析（图1c）
Molecular self-assembly of synthetic polymers in a selective solvent or through layer-by-layer approaches has attracted great interest.[1, 2] Most reported precursors for the self-assembly in selective solvents are amphiphilic linear/dendritic block copolymers.[3, 4] Recently, the covalent block precursors have been extended to supramolecular ones.[5] However, little attention has been paid to the molecular selfassembly of a homopolymer derived from only one type monomer. Is there any homopolymer that can spontaneously aggregate into highly ordered structures driven by noncovalent interactions? To answer this question, we synthesized a novel amphiphilic homopolymer and realized its aqueous self-assembly to form spherical micelles with a remarkably narrow size distribution. The resulting micelles exhibit smart redox-responsive properties, which can be exploited to rapidly deliver hydrophobic drugs into the nuclei of tumor cells and enhance the inhibition of cell proliferation. The monomer used is 2-[(2-hydroxyethyl)-disulfanyl] ethoxy-2-oxo-1, 3, 2-dioxaphospholane, which consists of both hydrophobic and hydrophilic moieties and can polymerize into a hyperbranched polyphosphate(HPHDP) through self-condensing ring-opening polymerization (SCROP).[6] HPHDP is an amphiphilic homopolymer with alternative hydrophobic disulfide and hydrophilic polyphosphate segments along the highly branched structure (Scheme 1). Three HPHDP samples with different molecular weights were synthesized. Characterization data of the different precursor samples and corresponding micelles are summarized in Table 1.[7] In general, the molecular-weight distribution of a hyperbranched polymer is very broad. However, the low-molecular-weight species in the products were removed by dialysis, so the Mw/Mn value of the final samples is equal to or less than 1.72. The degrees of branching (DBs) measured by NMR spectroscopy approach 0.5. Figure1a shows a typical transmission electron microscopy (TEM) image of HPHDP micelles, and Figure1b is the enlarged TEM image of only one micelle. It is interesting that the micelles are fairly homogeneous. Statistical analyses based on 100 micelles for each HPHDP sample (Figure 1c)