体内
连接器
生物物理学
部分
组合化学
光热治疗
聚乙二醇
材料科学
化学
纳米技术
生物化学
有机化学
生物
计算机科学
操作系统
生物技术
作者
Fengjun Sun,Yu Wang,Qianmei Wang,Xiaowen Wang,Pu Yao,Wei Feng,Yuan Qian,Xiaowei Qi,Sheng Chen,Wendan Pu,Rong Huang,Qing Dai,Jun Lv,Qian Wang,Wenhao Shen,Peiyuan Xia,Dinglin Zhang
标识
DOI:10.1021/acsami.1c21665
摘要
Photocleavable biomaterials and bioconjugates have been widely researched for tissue engineering, cell culture, and therapeutics delivery. However, most in vivo applications of these materials or conjugates require external irradiation, and some of the light sources used such as ultraviolet (UV) light have poor tissue penetration. To address these key limitations, we synthesized a photocleavable nanoprodrug using luminol (a luminescent donor), chlorambucil (CHL, i.e., an antitumor drug with a photocleavable linker), and polyethylene glycol-folic acid conjugates (a targeted moiety) loaded onto polyamidoamine (PAMAM). The synthesized nanoprodrug can smartly release its payloads through photocleavage of photoresponsive linker by UV light, which was produced in situ by reacting luminol with pathological reactive oxygen species (ROS). The luminescence performance and absorption spectrum of this nanoprodrug was characterized in detail. In vitro cellular assays verified that the nanoprodrugs could be efficiently internalized by 4T1 and MDA-MB-231 cells, and the CHL released from the nanoprodrugs could distinctly decrease cell viability through the damage of DNA in cells. In vivo animal experiments demonstrated that the nanoprodrugs were mainly accumulated at tumor sites, and the antitumor drug CHL could be smartly released from the nanoprodrugs through cleavage of photosensitive linkers at a high level of ROS. The released CHL significantly inhibited the growth of tumors without any obvious adverse effects. Our results provide a practicable strategy to expand the in vivo application of photocleavable biomaterials and bioconjugates.
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