Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
J Mater Chem B. 2020 Apr 14;8(14):2826-2833. doi: 10.1039/c9tb02163a. Epub 2020 Mar 13.
The combination of anticancer drugs and laser hyperthermia could lead to efficient cancer treatment with less-adverse effects. This study combined anticancer drug-loaded functional dendrimers and light-responsive gold nanorods to fabricate nanohybrids that can provide anticancer-drug delivery and subsequent heat generation under near-infrared laser irradiation. A condensation reaction was used to conjugate poly(ethylene glycol)-modified polyamidoamine dendrimers to carboxylated gold nanorod surfaces. Oleoyl groups were incorporated into dendrimers to improve the drug loading capacity. Doxorubicin loading capacity was improved by incorporation of oleoyl chains into dendrimers in the nanohybrid, indicating increased hydrophobic interaction between anticancer drugs and nanohybrids. The nanohybrids exhibited heat generation properties under near infrared laser irradiation. They released anticancer drugs over time. The combination of doxorubicin-loaded nanohybrids and laser irradiation showed markedly better cytotoxicity than that of the nanohybrids used with lasers and drug-loaded nanohybrids without the use of lasers. After intravenous or intratumoral injection of nanohybrids to tumor-bearing mice, a sharp temperature increase was observed at the tumor site under laser irradiation. Especially, intratumorally injected doxorubicin-loaded nanohybrids showed almost complete tumor growth suppression under laser irradiation. The results demonstrate that functional dendrimer-gold nanorod nanohybrids are promising as multi-functional nanomaterials to achieve synergistic effects of anticancer drugs and heat ablation to support effective cancer treatments.
抗癌药物与激光热疗相结合可能会带来高效低副作用的癌症治疗效果。本研究将载药功能树状大分子与光响应金纳米棒结合,制备纳米杂化物,在近红外激光照射下可提供抗癌药物输送和随后的热量产生。缩合反应将聚乙二醇修饰的聚酰胺胺树状大分子偶联到羧基化金纳米棒表面。将油酰基引入树状大分子以提高载药能力。通过将油酰基链引入纳米杂化物中的树状大分子,提高了载药能力,表明抗癌药物与纳米杂化物之间的疏水相互作用增强。纳米杂化物在近红外激光照射下表现出产热特性。它们会随着时间的推移释放抗癌药物。载药纳米杂化物与激光联合使用的组合表现出比激光和未使用激光的载药纳米杂化物更好的细胞毒性。将纳米杂化物静脉内或肿瘤内注射到荷瘤小鼠后,在激光照射下肿瘤部位的温度急剧升高。特别是,肿瘤内注射的载多柔比星纳米杂化物在激光照射下几乎完全抑制了肿瘤生长。结果表明,功能树状大分子-金纳米棒纳米杂化物有望成为多功能纳米材料,以实现抗癌药物和热消融的协同作用,支持有效的癌症治疗。