Advances in Functional Metal‐Organic Frameworks Based On‐Demand Drug Delivery Systems for Tumor Therapeutics

Abstract

Dual on‐demand delivery of therapeutic cargos and energy by transporters can latently mitigate side effects and provide the unique aspects required for precision medicine. To achieve this goal, metal‐organic frameworks (MOFs), hybrid materials constructed from metal ions and polydentate organic linkers, have attracted attention for controlled drug release and energy delivery in tumors. With appropriate characteristics such as tunable pore size, high surface area, and tailorable composition, therapeutic agents (drug molecules or responsive agents) can be effectively encapsulated in MOFs. Based on their intrinsic properties, many physically or chemically responsive agents are able to achieve precise on‐demand drug release and energy generation (thermal or dynamic therapy) using MOFs (as energy absorbers). Herein, the results obtained with various stimuli‐responsive MOFs (including materials from the Institute Lavoisier [MIL], zeolitic imidazolate frameworks [ZIFs], MOFs from the University of Oslo [UiO], and other MOFs) used for tumor suppression are summarized. Furthermore, with the appropriate stimulus, catalytic therapy (caused by the Fenton reaction induced by MOFs) can be provided via the utilization of existing high levels of H2O2 in cancer cells, which potentially elicits immune responses. In addition, the issues impeding clinical translation are also discussed, including the need to overcome tumor heterogeneity and to recognize the innate immune system and possible effects. As the references reveal, additional comprehensive strategies and studies are needed to enable broad applications and potent translational developments.

Nanosized metal–organic frameworks as unique platforms for bioapplications

“…Therefore, the development of DDSs with targeting capabilities and controlled release features would address the problem of side effects and improve the effectiveness of the treatments. 106 However, whereas the targeting functionalities are widely considered and explored, the controlled release in DDSs is still in its infancy. To date, some systems have shown efficient and controlled drug release features in response to external stimuli.…”

Programmed Catalytic Therapy-Mediated ROS Generation and T-Cell Infiltration in Lung Metastasis by a Dual Metal-Organic Framework (MOF) Nanoagent

“…In this regard, the reactive oxygen species (ROS), which plays a typical role in the cellular signaling-derivatized oxygen molecules, served as an oxidative damager in excessive expression (specifically H 2 O 2 ), and could lead to potent oxidative harm within cancer cells [ 15 , 16 ]. Such ROS-responsive biological targets have attracted great attention in the redox chemistry of cancer therapeutics via promoting the intracellular H 2 O 2 conversion to •OH [ 17 , 18 , 19 ]. It can induce a Fenton-like reaction in the tumor in which H 2 O 2 is disproportionated to toxic •OH, facilitating oxidization and damaging intracellular proteins and organelles [ 20 ].…”

Mechanochemical Synthesis of Fluorine-Containing Co-Doped Zeolitic Imidazolate Frameworks for Producing Electrocatalysts

“…Zeolitic imidazole frameworks (ZIFs) ( Park et al, 2006 ), a class of metal organic frameworks (MOFs), consisting of metal nodes, linked by imidazole-based linkers can serve as templates, which can be converted in to M-N-C ORR catalysts by pyrolysis. ZIF materials are commonly used for gas storage ( Eddaoudi et al, 2002 ) and separation ( Keskin et al, 2010 ), oil spill cleaning ( Mondal et al, 2017 ), catalysis ( Farrusseng et al, 2009 ; Hu et al, 2020 ), sensing ( Chapartegui-Arias et al, 2019 ; Zhang et al, 2020 ), and drug delivery ( Hao et al, 2021 ; Ibrahim et al, 2017 ; Nirosha Yalamandala et al, 2021 ), as precursors for electrocatalysis ( Li et al, 2016 ; Wang et al, 2014 ; Zhao et al, 2014 ) and as stimuli-responsive materials ( Iacomi and Maurin, 2021 ). The crystal structures of these porous coordination polymers are based on the topology nets of zeolites.…”