School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, Jiangsu, 212013, China.
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, 510275, China.
Small. 2018 Mar;14(13):e1703968. doi: 10.1002/smll.201703968. Epub 2018 Feb 12.
Multifunctional nanomaterials with efficient tumor-targeting and high antitumor activity are highly anticipated in the field of cancer therapy. In this work, a synergetic tumor-targeted, chemo-photothermal combined therapeutic nanoplatform based on a dynamically PEGylated, borate-coordination-polymer-coated polydopamine nanoparticle (PDA@CP-PEG) is developed. PEGylation on the multifunctional nanoparticles is dynamically achieved via the reversible covalent interaction between the surface phenylboronic acid (PBA) group and a catechol-containing poly(ethylene glycol) (PEG) molecule. Due to the acid-labile PBA/catechol complex and the weak-acid-stable PBA/sialic acid (SA) complex, the nanoparticles can exhibit a synergetic targeting property for the SA-overexpressed tumor cells, i.e., the PEG-caused "passive targeting" and PBA-triggered "active targeting" under the weakly acidic tumor microenvironment. In addition, the photothermal effect of the polydopamine core and the doxorubicin-loading capacity of the porous coordination polymer layer endow the nanoparticles with the potential for chemo-photothermal combination therapy. As expected, the in vitro and in vivo studies both verify that the multifunctional nanoparticles possess relatively lower systematic toxicity, efficient tumor targeting ability, and excellent chemo-photothermal activity for tumor inhibition. It is believed that these multifunctional nanoparticles with synergetic tumor targeting property and combined therapeutic strategies would provide an insight into the design of a high-efficiency antitumor nanoplatform for potential clinical applications.
多功能纳米材料具有高效的肿瘤靶向和抗肿瘤活性,在癌症治疗领域备受期待。在这项工作中,开发了一种基于动态聚乙二醇化、硼酸配位聚合物涂层聚多巴胺纳米粒子(PDA@CP-PEG)的协同肿瘤靶向、化疗-光热联合治疗的纳米平台。多功能纳米粒子上的聚乙二醇化是通过表面苯硼酸(PBA)基团与含儿茶酚的聚乙二醇(PEG)分子之间的可逆共价相互作用来动态实现的。由于 PBA/儿茶酚复合物的酸不稳定和 PBA/唾液酸(SA)复合物的弱酸稳定,纳米粒子可以表现出对 SA 过表达肿瘤细胞的协同靶向特性,即在弱酸性肿瘤微环境下,PEG 引起的“被动靶向”和 PBA 触发的“主动靶向”。此外,聚多巴胺核的光热效应和多孔配位聚合物层的载药能力赋予了纳米粒子用于化疗-光热联合治疗的潜力。正如预期的那样,体外和体内研究都验证了多功能纳米粒子具有相对较低的系统毒性、高效的肿瘤靶向能力和优异的肿瘤抑制化疗-光热活性。相信这种具有协同肿瘤靶向性和联合治疗策略的多功能纳米粒子将为高效抗肿瘤纳米平台的设计提供新的思路,有望应用于临床。
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