Combinational application of metal–organic frameworks‐based nanozyme and nucleic acid delivery in cancer therapy

Abstract

The rapid development of nanotechnology has generated numerous ideas for cancer treatment, and a wide variety of relevant nanoparticle platforms have been reported. Metal–organic frameworks (MOFs) have been widely investigated as an anti‐cancer drug delivery vehicle owing to their unique porous hybrid structure, biocompatibility, structural tunability, and multi‐functionality. MOF materials with catalytic activity, known as nanozymes, have applications in photodynamic and chemodynamic therapy. Nucleic acids have also attracted increasing research attention owing to their programmability, ease of synthesis, and versatility. A variety of functional DNAs and RNAs have been applied both therapeutically (gene‐targeting drugs for cancer treatment) and nontherapeutically (used as modified materials to enhance the therapeutic effects of other nanomedicines). The combined use of MOFs and functional nucleic acids have been extensively investigated and has been associated with excellent tumor‐suppressor activity in various treatment methods. In this review, we summarize the progress in the research and development of tumor therapy based on MOFs and nucleic acid delivery over recent years, focusing on the combinational use of different delivery and design strategies for MOF/therapeutic nucleic acid platforms. We further summarize the strategies for combining MOFs (universal carrier, functional carrier) and nucleic acids (therapeutic nucleic acids, nontherapeutic nucleic acids) and discuss the corresponding therapeutic effects in cancer treatment. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies

Perspectives of metal-organic framework nanosystem to overcome tumor drug resistance

“…We summarize the recent MOF-based materials to overcome cancer drug resistance in Table 1. For example, Lian et al used PCN-333(Al) (PCN, porous coordination network) as the nanocarrier to load tyrosinase (TYR) for synthesizing an enzyme-MOF nanoreactor, converting the non-toxic prodrug paracetamol (APAP) to 4-acetamido-o-benzoquinone (AOBQ) in vivo [33] . They demonstrated that AOBQ induced the depletion of GSH and oxidative stress, attracting ROS-generated CDT to poison cancer cells.…”

“…Among them, MOFs, as an emerging class of nanomaterials, have gained the broad interest of many researchers owing to their high specific surface area, tunable porous structure, satisfactory stability, and biocompatibility. In particular, MOFs have shown great potential and advantages as nanocarriers for drug delivery and protection, such as encapsulation of drugs, direct assembly of drug molecules as organic ligands [35] , post synthesis [33] , and surface modification [36] . Up to now, the MOF-based drug delivery system (DDS) has been employed to deliver drugs such as cisplatin [37] , doxorubicin (DOX) [38][39][40] , biomolecular agents [2,[41][42][43] , and immunosuppressants [44,45] .…”

“…With the rapid progress of nanotechnology, multifunctional nanoparticles (NPs) enable selective delivery of therapeutic and/or diagnostic drugs to target tumor sites, making precision therapy possible. To date, many organic/inorganic nanomaterials [ 18 - 20 ] , including polysaccharides [ 21 , 22 ] , proteins [ 23 , 24 ] , polymers [ 25 ] , metals and metal oxides [ 26 , 27 ] , mesoporous silica [ 28 ] , engineering macrophages [ 29 ] , nucleic acid nanodevices [ 30 - 32 ] , and metal-organic frameworks (MOFs) [ 33 , 34 ] , have been extensively designed to address physicochemical issues associated with free drugs, tumor drug resistance, and biological barriers during delivery. Among them, MOFs, as an emerging class of nanomaterials, have gained the broad interest of many researchers owing to their high specific surface area, tunable porous structure, satisfactory stability, and biocompatibility.…”

Metal‐Organic Frameworks for Gene Therapy and Detection

“…[15] Whilst the large surface and chemical groups of a MOF facilitate functionalization with chemical moieties that can promote nucleic acid uptake by cells. [7,16] Another advantage of MOF modification is that this can enable targeted and controlled release of the loaded nucleic acids. [6c,17] Thirdly, MOFs can be used to facilitate escape of nucleic acids from endo/lysosomes thereby improving the transfection efficiency.…”

Nanoscale metal-organic frameworks for the delivery of nucleic acids to cancer cells

“…In a nutshell, all the steps involved in the preparation of drug-loaded and surface functionalized nanoMOFs were “green,” making them attractive for drug delivery, and especially for the hydrolysable TNAs which need to be protected from nuclease degradation when exposed to biological media. However, there are still scarce examples of nanoMOFs engineered as carriers for TNAs ( Peng et al, 2018 ; Teplensky et al, 2019 ) with several works reporting the MOF-assisted delivery of pooled siRNAs ( He et al, 2014 ), single-stranded DNAs ( Peng et al, 2018 ), as well as miRNAs and DNAzymes ( Ni et al, 2022 ).…”