Intracellular Mutual Amplification of Oxidative Stress and Inhibition Multidrug Resistance for Enhanced Sonodynamic/Chemodynamic/Chemo Therapy

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 18; no. 13; pp. e2107160 - n/a
• Main Authors: Guan, Shaoqi, Liu, Xijian, Li, Chunlin, Wang, Xingyan, Cao, Dongmiao, Wang, Jinxia, Lin, Lizhou, Lu, Jie, Deng, Guoying, Hu, Junqing
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.04.2022
• Subjects: Biodegradability; Cell Line, Tumor; chemodynamic therapy; Chemotherapy; Composite structures; Decomposition reactions; Doxorubicin; Drug Resistance, Multiple; electron transport chain; Glutathione; Glycoproteins; Hydrogen peroxide; Hypoxia; Magnetic resonance imaging; Manganese Compounds; Manganese dioxide; multidrug resistance; Nanocomposites; Nanotechnology; Oxidation resistance; Oxidative Stress; Oxides - chemistry; Reagents; sonodynamic therapy; Tumor Microenvironment; Tumors; multidrug resistance; electron transport chain; sonodynamic therapy; chemodynamic therapy; oxidative stress
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202107160

Emerging noninvasive treatments, such as sonodynamic therapy (SDT) and chemodynamic therapy (CDT), have developed as promising alternatives or supplements to traditional chemotherapy. However, their therapeutic effects are limited by the hypoxic environment of tumors. Here, a biodegradable nanocomposite‐mesoporous zeolitic‐imidazolate‐framework@MnO2/doxorubicin hydrochloride (mZMD) is developed, which achieves enhanced SDT/CDT/chemotherapy through promoting oxidative stress and overcoming the multidrug resistance. The mZMD decomposes under both ultrasound (US) irradiation and specific reactions in the tumor microenvironment (TME). The mZM composite structure reduces the recombination rate of e− and h+ to improve SDT. MnO2 not only oxidizes glutathione in tumor cells to enhance oxidative stress, but also converts the endogenic H2O2 into O2 to improve the hypoxic TME, which enhances the effects of chemotherapy/SDT. Meanwhile, the generated Mn2+ catalyzes the endogenic H2O2 into ·OH for CDT, and acts as magnetic resonance imaging agent to guide therapy. In addition, dissociated Zn2+ further breaks the redox balance of TME, and co‐inhibits the expression of P‐glycoprotein (P‐gp) with generated ROS to overcome drug resistance. Thus, the as‐prepared intelligent biodegradable mZMD provides an innovative strategy to enhance SDT/CDT/chemotherapy. A biodegradable theranostic agent is developed based on mesoporous zeolitic‐imidazolate‐framework@MnO2/doxorubicin hydrochloride (ZIF‐90@MnO2/DOX), which achieves enhanced sonodynamic therapy/chemodynamic therapy/chemotherapy through promoting oxidative stress and overcoming the multidrug resistance, and offers an innovative insight into the development of biomaterials for reactive oxygen species‐related therapeutic modalities.