Synthesis of polyorganophosphazenes and preparation of their polymersomes for reductive/acidic dual-responsive anticancer drugs release
Synthesis of polyorganophosphazenes and preparation of their polymersomes for reductive/acidic dual-responsive anticancer drugs release
复制标题
DOI：
10.1007/s10853-020-04595-6
复制
发表时间：
2020-04-03
影响因子：
4.5
通讯作者：
Elsharaarani, Tarig
中科院分区：
文献类型：
--
作者：
Khan, Rizwan Ullah;Yu, Haojie;Elsharaarani, Tarig
与正常人体细胞相比，癌细胞具有还原和酸性环境。还原/酸性响应性多聚体的开发将在癌症治疗中发挥重要作用，以触发负载药物的释放。在我们的工作中，我们合成了三种不同的还原/酸性双响应聚合物，即不同侧基摩尔比的聚[(mpeg-SS-氨基)(N，N-二异丙基乙二氨基)磷腈](PPPP)。用H-1核磁共振、P-31核磁共振、FT-IR和凝胶渗透色谱(GPC)对其结构进行了表征。之后，PPPP可以自组装成载药量高、包封率高的亲水/疏水抗癌药物聚合体。使用亲水性抗癌药物盐酸阿霉素(DOX CENTER Dot HCl)和疏水性药物阿霉素。这些基于PPDPS的聚合体表现出还原/酸性刺激响应的抗癌药物释放。此外，这些聚合体还表现出合适的流体力学直径，这将有助于血液中的长期循环，因为它避免了肾脏清除，并由于增强了通透性和滞留效应而与血管切片中的肿瘤细胞密切接触。综上所述，这些发展起来的聚合体可能为抗癌药物的输送提供一个有效的平台。
Cancer cells have reductive and acidic environments as compared to the normal body cells. Development of reductive/acidic responsive polymersomes will play a major role in cancer therapy to trigger the release of the loaded drug. In our work, we synthesized three different reductive/acidic dual-responsive polymers, poly[(mPEG-SS-amino) (N,N-diisopropylethylenediamino)phosphazenes] (PPDPs) in different mole ratios of side groups. These PPDPs were characterized by H-1 NMR, P-31 NMR, FT-IR and GPC. After that, the PPDPs were allowed to self-assemble into drug-loaded polymersomes with high loading content and encapsulation efficiency of hydrophilic/hydrophobic anticancer drugs. The hydrophilic anticancer drug doxorubicin hydrochloride (DOX center dot HCl) and hydrophobic drug doxorubicin were used. These PPDPs-based polymersomes showed reductive/acidic stimuli-responsive release of anticancer drugs. Moreover, these polymersomes also exhibited suitable hydrodynamic diameters, which will facilitate the longtime circulation in bloodstream due to avoiding renal clearance and close contact to the tumor cells in vascular sections due to enhanced permeability and retention effect. Collectively, these developed polymersomes may provide an effective platform for anticancer drugs delivery.