Qin Yanzhe, Peng Xinwen
State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou 510641, China.
The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, School of Environment and Energy, Guangzhou Higher Education Mega Centre, South China University of Technology, Guangzhou 510006, China.
ACS Biomater Sci Eng. 2020 Mar 9;6(3):1582-1589. doi: 10.1021/acsbiomaterials.0c00090. Epub 2020 Feb 17.
Patients with cancer suffer from severe side effects and reduced life quality, as chemotherapeutic drugs are cytotoxic toward normal cells as well as toward cancer cells. In recent years, nanoparticles have been explored as targeted drug delivery systems; however, problems such as toxicity and instability prevent their practical application. Here, we report the synthesis of cholesteryl-carboxymethyl xylan (CCMX) via an esterification reaction between the carboxyl group of carboxymethyl xylan and the hydroxyl group of cholesterol to form biocompatible micelles as a vehicle for targeted drugs. With its critical micelle concentration (CMC) depending on the degree of substitution (DS) of cholesteryl and ranging from 0.0024 to 0.017 mg/mL, CCMX could self-assemble and form nanoscale micelles in aqueous media. Taking doxorubicin (DOX) as a model drug, the drug encapsulation efficiency (EE%) of CCMX-3 (DS of 0.35 for cholesteryl) reached 91.3%, and this system exhibited excellent internalization ability, as verified by tumor cellular uptake tests. The results of in vitro cytotoxicity and in vivo antitumor activity tests of nude mice demonstrated that CCMX-3/DOX micelles effectively suppressed the growth of tumor cells by maintaining the cytotoxicity of commercial DOX injection while reducing the toxicity against normal cells and increasing the survival time.
癌症患者会遭受严重的副作用，生活质量下降，因为化疗药物对正常细胞和癌细胞都具有细胞毒性。近年来，纳米颗粒已被探索用作靶向给药系统；然而，毒性和不稳定性等问题阻碍了它们的实际应用。在此，我们报告了通过羧甲基木聚糖的羧基与胆固醇的羟基之间的酯化反应合成胆固醇基-羧甲基木聚糖（CCMX），以形成生物相容性胶束作为靶向药物的载体。CCMX的临界胶束浓度（CMC）取决于胆固醇的取代度（DS），范围为0.0024至0.017mg/mL，在水性介质中CCMX可以自组装并形成纳米级胶束。以阿霉素（DOX）为模型药物，CCMX-3（胆固醇的DS为0.35）的药物包封率（EE%）达到91.3%，并且通过肿瘤细胞摄取试验证实该系统具有优异的内化能力。裸鼠的体外细胞毒性和体内抗肿瘤活性试验结果表明，CCMX-3/DOX胶束在保持市售DOX注射液细胞毒性的同时，有效抑制肿瘤细胞生长，降低对正常细胞的毒性，并延长生存时间。
