State Key Laboratory for Modification of Chemical, Fibers and Polymer Materials, Donghua University, Shanghai 201620, People's Republic of China; College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.
Adv Healthc Mater. 2013 Sep;2(9):1267-76. doi: 10.1002/adhm.201200389. Epub 2013 Feb 28.
We report the use of multifunctional dendrimer-modified multi-walled carbon nanotubes (MWCNTs) for targeted and pH-responsive delivery of doxorubicin (DOX) into cancer cells. In this study, amine-terminated generation 5 poly(amidoamine) (PAMAM) dendrimers modified with fluorescein isothiocyanate (FI) and folic acid (FA) were covalently linked to acid-treated MWCNTs, followed by acetylation of the remaining dendrimer terminal amines to neutralize the positive surface potential. The formed multifunctional MWCNTs (MWCNT/G5.NHAc-FI-FA) were characterized via different techniques. Then, the MWCNT/G5.NHAc-FI-FA was used to load DOX for targeted and pH-responsive delivery to cancer cells overexpressing high-affinity folic acid receptors (FAR). We showed that the MWCNT/G5.NHAc-FI-FA enabled a high drug payload and encapsulation efficiency both up to 97.8% and the formed DOX/MWCNT/G5.NHAc-FI-FA complexes displayed a pH-responsive release property with fast DOX release under acidic environment and slow release at physiological pH conditions. Importantly, the DOX/MWCNT/G5.NHAc-FI-FA complexes displayed effective therapeutic efficacy, similar to that of free DOX, and were able to target to cancer cells overexpressing high-affinity FAR and effectively inhibit the growth of the cancer cells. The synthesized multifunctional dendrimer-modified MWCNTs may be used as a targeted and pH-responsive delivery system for targeting therapy of different types of cancer cells.
我们报告了多功能树状大分子修饰的多壁碳纳米管（MWCNTs）在将阿霉素（DOX）靶向递送至癌细胞中的应用，该递药系统具有 pH 响应性。在这项研究中，用荧光素异硫氰酸酯（FI）和叶酸（FA）修饰的胺端基第五代聚酰胺-胺（PAMAM）树状大分子通过共价键连接到酸处理的 MWCNTs 上，然后用乙酰化反应中和剩余树状大分子末端胺的正表面电势。通过不同的技术对形成的多功能 MWCNTs（MWCNT/G5.NHAc-FI-FA）进行了表征。然后，MWCNT/G5.NHAc-FI-FA 被用来负载 DOX，以实现对高亲和力叶酸受体（FAR）过表达的癌细胞的靶向和 pH 响应性递药。我们表明，MWCNT/G5.NHAc-FI-FA 能够实现高载药量和高达 97.8%的包封效率，形成的 DOX/MWCNT/G5.NHAc-FI-FA 复合物具有 pH 响应性释放特性，在酸性环境下快速释放 DOX，在生理 pH 条件下缓慢释放。重要的是，DOX/MWCNT/G5.NHAc-FI-FA 复合物表现出与游离 DOX 相似的有效治疗效果，能够靶向高亲和力 FAR 过表达的癌细胞，并有效抑制癌细胞的生长。合成的多功能树状大分子修饰的 MWCNTs 可用作靶向治疗不同类型癌细胞的靶向和 pH 响应性递药系统。
