Zhang Jin, Tang Xiaoyue, Huang Chuanqing, Liu Zeyu, Ye Yong
Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China.
Pharmaceutics. 2020 Jul 20;12(7):680. doi: 10.3390/pharmaceutics12070680.
Oleic acid (OA) as main component of plant oil is an important solvent but seldom used in the nanocarrier of anticancer drugs because of strong hydrophobicity and little drug release. In order to develop a new type of OA nanomaterial with dual responses to pH and near infrared light (NIR) to achieve the intelligent delivery of anticancer drugs. The novel OA copolymer (mPEG-PEI-(NBS, OA)) was synthesized by grafting OA and -nitrobenzyl succinate (NBS) onto mPEGylated polyethyleneimine (mPEG-PEI) by amidation reaction. It was further conjugated with NaYF:Yb/Er nanoparticles, and encapsulated doxorubicin (DOX) through self-assembly to make upconversion nanomicelles with dual response to pH and NIR. Drug release behavior of DOX, physicochemical characteristics of the nanomicelles were evaluated, along with its cytotoxic profile, as well as the degree of cellular uptake in A549 cells. The encapsulation efficiency and drug loading capacity of DOX in the nanomicelles were 73.84% ± 0.58% and 4.62% ± 0.28%, respectively, and the encapsulated DOX was quickly released in an acidic environment exposed to irradiation at 980 nm. The blank nanomicelles exhibited low cytotoxicity and excellent biocompatibility by MTT assay against A549 cells. The DOX-loaded nanomicelles showed remarkable cytotoxicity to A549 cells under NIR, and promoted the cellular uptake of DOX into the cytoplasm and nucleus of cancer cells. OA copolymer can effectively deliver DOX to cancer cells and achieve tumor targeting through a dual response to pH and NIR.
油酸（OA）作为植物油的主要成分，是一种重要的溶剂，但由于其强疏水性和药物释放少，很少用于抗癌药物的纳米载体。为了开发一种对pH值和近红外光（NIR）具有双重响应的新型OA纳米材料，以实现抗癌药物的智能递送。通过酰胺化反应将OA和琥珀酸 - 硝基苄酯（NBS）接枝到聚乙二醇化聚乙烯亚胺（mPEG - PEI）上，合成了新型OA共聚物（mPEG - PEI - (NBS, OA)）。它进一步与NaYF:Yb/Er纳米颗粒共轭，并通过自组装包封阿霉素（DOX），制成对pH和NIR具有双重响应的上转换纳米胶束。评估了DOX的药物释放行为、纳米胶束的物理化学特性，以及其细胞毒性概况，以及在A549细胞中的细胞摄取程度。纳米胶束中DOX的包封率和载药量分别为73.84%±0.58%和4.62%±0.28%，并且在980nm照射下暴露于酸性环境中时，包封的DOX会快速释放。通过MTT法检测，空白纳米胶束对A549细胞表现出低细胞毒性和优异的生物相容性。负载DOX的纳米胶束在近红外光下对A549细胞表现出显著的细胞毒性，并促进DOX进入癌细胞的细胞质和细胞核的细胞摄取。OA共聚物可以通过对pH和近红外光的双重响应，有效地将DOX递送至癌细胞并实现肿瘤靶向。
