Tumor‐Specific Drug Release and Reactive Oxygen Species Generation for Cancer Chemo/Chemodynamic Combination Therapy

• Published in: Advanced science 2019-03, Vol.6 (5), p.1801986-n/a
• Main Authors: Wang, Sheng, Wang, Zhantong, Yu, Guocan, Zhou, Zijian, Jacobson, Orit, Liu, Yijing, Ma, Ying, Zhang, Fuwu, Chen, Zhi‐Yi, Chen, Xiaoyuan
• Format: Article
• Language: English
• Subjects: Aqueous solutions; Cancer therapies; Catalysis; Chemotherapy; Communication; Communications; Drug delivery systems; Drugs; Fenton reaction; nanomedicines; Nanoparticles; Polymerization; polyprodrugs; reactive oxygen species; triggered drug release; Tumors
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.201801986

The combination of chemotherapeutic drugs and reactive oxygen species (ROS) is a promising strategy to achieve improved anticancer effect. Herein, a nanomedicine (LaCIONPs) that can achieve tumor‐specific chemotherapeutic drug release and ROS generation is developed for cancer chemo/chemodynamic combination therapy. The LaCIONPs are constructed by encapsulation of iron oxide nanoparticles (IONPs) and β‐lapachone (La) in nanostructure assembled by hydrogen peroxide (H2O2)‐responsive polyprodrug and pH‐responsive polymer. Through the enhanced permeability and retention effect, the nanosized LaCIONPs can accumulate in tumor tissue. After the LaCIONPs are internalized by tumor cells, the structure of LaCIONPs is disintegrated in acidic intracellular environment, leading to rapid release of La and iron ions. Then the released La generates massive H2O2 through tumor specific catalysis. On the one hand, H2O2 further reacts with iron ions to produce highly toxic hydroxyl radicals for chemodynamic therapy. On the other hand, H2O2 also activates the release of camptothecin from the polyprodrug for chemotherapy. The potent antitumor effect of the LaCIONPs is demonstrated by both in vitro and in vivo results. Therefore, the LaCIONP is a promising nanomedicine for tumor‐specific chemo/chemodynamic combination therapy. A pH and hydrogen peroxide (H2O2) dual‐responsive nanomedicine is developed for tumor‐specific chemo/chemodynamic combination therapy. Once the nanomedicines enter cancer cells through endocytosis, their structure is disintegrated, resulting in rapid release of β‐lapachone and iron ions. The β‐lapachone generates H2O2 inside cells, which further produces highly toxic hydroxyl radicals through the Fenton reaction and activates chemotherapeutic drug release.