Biodegradable Metal–Organic‐Framework‐Gated Organosilica for Tumor‐Microenvironment‐Unlocked Glutathione‐Depletion‐Enhanced Synergistic Therapy. Issue 12 (11th February 2022)

• Record Type: Journal Article
• Authors: Ma, Yuanyuan; Su, Zheng; Zhou, Liming; He, Liangcan; Hou, Zhenyu; Zou, Jianhua; Cai, Yu; Chang, Di; Xie, Jinbing; Zhu, Chen; Fan, Wenpei; Chen, Xiaoyuan; Ju, Shenghong
• Is Part Of: Advanced materials. Volume 34:Issue 12(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-11
• Subjects: controllable release -- mesoporous organosilica -- metal–organic frameworks -- synergistic therapy -- tumor microenvironment; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adma.202107560
• Languages: English
• ISSNs: 0935-9648

Abstract

Abstract: The clinical employment of cisplatin ( cis ‐diamminedichloroplatinum(II) (CDDP)) is largely constrained due to the non‐specific delivery and resultant serious systemic toxicity. Small‐sized biocompatible and biodegradable hollow mesoporous organosilica (HMOS) nanoparticles show superior advantages for targeted CDDP delivery but suffer from premature CDDP leakage. Herein, the smart use of a bimetallic Zn 2+ /Cu 2+ co‐doped metal–organic framework (MOF) is made to block the pores of HMOS for preventing potential leakage of CDDP and remarkably increasing the loading capacity of HMOS. Once reaching the acidic tumor microenvironment (TME), the outer MOF can decompose quickly to release CDDP for chemotherapy against cancer. Besides, the concomitant release of dopant Cu 2+ can deplete the intracellular glutathione (GSH) for increased toxicity of CDDP as well as catalyzing the decomposition of intratumoral H2 O2 into highly toxic OH for chemodynamic therapy (CDT). Moreover, the substantially reduced GSH can also protect the yielded OH from scavenging and thus greatly improve the OH‐based CDT effect. In addition to providing a hybrid HMOS@MOF nanocarrier, this study is also expected to establish a new form of TME‐unlocked nanoformula for highly efficient tumor‐specific GSH‐depletion‐enhanced synergistic chemotherapy/chemodynamic therapy. Abstract : A tumor microenvironment (TME)‐unlocked nanoformula is judiciously designed by the smart use of a biodegradable metal–organic framework to gate the pores of sub‐50 nm hollow mesoporous organosilica nanoparticles. This method can not only realize acidic‐TME‐responsive cisplatin release, but also deplete glutathione and simultaneously catalyze the generation of OH via Cu 2+ for highly efficient tumor‐specific synergistic chemotherapy/chemodynamic therapy against cancer with negligible biosafety concerns.