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用于抗癌药物递送的纳米级聚(4-羟基丁酸酯)-甲氧基聚乙二醇载体

Nanoscale poly(4-hydroxybutyrate)-mPEG carriers for anticancer drugs delivery.

作者信息

Shah Mohsin, Ullah Najeeb, Choi Mun Hwan, Yoon Sung Chul

出版信息

J Nanosci Nanotechnol. 2014 Nov;14(11):8416-21. doi: 10.1166/jnn.2014.9924.

DOI:10.1166/jnn.2014.9924
PMID:25958538
Abstract

Despite several advancements in chemotherapy, cancer is still the second most frequent cause of mortality worldwide. Drug delivery to solid tumors is one of the most challenging aspects in cancer therapy. In pharmaceutical industries biodegradable polymeric nanoparticles as drug carriers have attracted great research interest because of their biocompatibility, biodegradability and sustained release of drugs. In our study we prepared poly(4-hydroxybutyrate)-mPEG (P(4HB)-mPEG) nanocarriers for the delivery of cisplatin as anticancer drug to mouse hippocampal HT22 cells. P(4HB) is more suitable candidate to be utilized in pharmaceutical industries due to its wide medical applications. P(4HB) is a homopolymer of 4-hydroxybutyrate (4HB), and belongs to a diverse class of materials called polyhydroxyalkanoates (PHA) produced by microorganisms inside the cells as energy storage materials. P(4HB) has certain unique properties such as biocompatibility and rapid in vivo degradation, which differentiate it from others PHA based polymers. Novel amorphous amphiphilic block copolymer P(4HB)-mPEG nanocarriers were prepared and characterized. Flow cytometry, and confocal microscopy revealed a suppression effect by the cisplatin loaded nanocarriers on HT22 cell growth, and enhancement of apoptotic process of the cells compared to free drug treated cells. The amorphous polymeric nanocarriers could be effective vehicles for the sustained delivery of toxic anticancer drugs for the therapy of cancer.

摘要

尽管化疗取得了多项进展,但癌症仍是全球第二大常见死因。将药物输送到实体瘤是癌症治疗中最具挑战性的方面之一。在制药行业,可生物降解的聚合物纳米颗粒作为药物载体因其生物相容性、生物可降解性和药物缓释性而引起了极大的研究兴趣。在我们的研究中,我们制备了聚(4-羟基丁酸酯)-甲氧基聚乙二醇(P(4HB)-mPEG)纳米载体,用于将顺铂作为抗癌药物输送到小鼠海马体HT22细胞。由于其广泛的医学应用,P(4HB)是更适合在制药行业中使用的候选材料。P(4HB)是4-羟基丁酸酯(4HB)的均聚物,属于一类由细胞内微生物产生的称为聚羟基脂肪酸酯(PHA)的多种材料,作为能量储存材料。P(4HB)具有某些独特的性质,如生物相容性和在体内的快速降解,这使其与其他基于PHA的聚合物有所不同。制备并表征了新型无定形两亲性嵌段共聚物P(4HB)-mPEG纳米载体。流式细胞术和共聚焦显微镜显示,与游离药物处理的细胞相比,负载顺铂的纳米载体对HT22细胞生长有抑制作用,并增强了细胞的凋亡过程。无定形聚合物纳米载体可能是用于持续递送有毒抗癌药物以治疗癌症的有效载体。

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