Poly(styrene-co-maleic acid)-based pH-sensitive liposomes mediate cytosolic delivery of drugs for enhanced cancer chemotherapy
Poly(styrene-co-maleic acid)-based pH-sensitive liposomes mediate cytosolic delivery of drugs for enhanced cancer chemotherapy
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DOI：
10.1016/j.ijpharm.2012.07.059
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发表时间：
2012-10-15
影响因子：
5.8
通讯作者：
Guha, Sujoy K.
中科院分区：
文献类型：
--
作者：
Banerjee, Shubhadeep;Sen, Kacoli;Guha, Sujoy K.
ph响应聚合物使脂质体具有ph敏感性，并通过在细胞内核内体内发现的轻度酸性条件下与血管内膜融合，促进被封装载荷的细胞内释放。本研究报告使用高分子量聚苯乙烯-共马来酸（SMA），其表现出从带电扩展结构到不带电球体的构象转变，低于其pK(1)值，赋予脂质体ph敏感特性。共聚物链构象的变化导致脂质体在轻度酸性pH下由于囊泡融合和/或膜双层内的通道形成而不稳定，并最终导致被封装货物的释放。与其他聚合物脂质体不同，这些囊泡在血清中保持了它们的pH敏感性和稳定性，并且在生理pH下没有溶血活性。在内体pH下，由于sma脂质体诱导的双分子层组织改变导致球型细胞形成，导致红细胞溶解，这表明这些囊泡具有通过内体不稳定介导生物活性分子的胞质输送的潜力。与纯脂质体相比，负载sma的脂质体表现出优异的细胞相容性，在结肠癌细胞HT-29中有效地递送化疗药物5-氟尿嘧啶（5-FU）。这增加了药物的细胞可利用性，导致细胞凋亡增加，并突出了基于sma的囊泡的临床潜力。(c) 2012 Elsevier B.V.版权所有
pH-responsive polymers render liposomes pH-sensitive and facilitate the intracellular release of encapsulated payload by fusing with endovascular membranes under mildly acidic conditions found inside cellular endosomes. The present study reports the use of high-molecular weight poly(styrene-co-maleic acid) (SMA), which exhibits conformational transition from a charged extended structure to an uncharged globule below its pK(1) value, to confer pH-sensitive property to liposomes. The changes in the co-polymer chain conformation resulted in destabilization of the liposomes at mildly acidic pH due to vesicle fusion and/or channel formation within the membrane bilayer, and ultimately led to the release of the encapsulated cargo. The vesicles preserved their pH-sensitivity and stability in serum unlike other polymer-based liposomes and exhibited no hemolytic activity at physiological pH. The lysis of RBCs at endosomal pH due to SMA-based liposome-induced alterations in the bilayer organization leading to spherocyte formation indicated the potential of these vesicles to mediate cytosolic delivery of bio-active molecules through endosome destabilization. The SMA-loaded liposomes exhibiting excellent cytocompatibility, efficiently delivered chemotherapeutic agent 5-Fluorouracil (5-FU) within colon cancer cells HT-29 in comparison to neat liposomes. This caused increased cellular-availability of the drug, which resulted in enhanced apoptosis and highlighted the clinical potential of SMA-based vesicles. (c) 2012 Elsevier B.V. All rights reserved.