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Dihydroartemisinin (DHA), a compound extracted from the herbal medicine Artemisia annua, has shown promise as a clinical treatment strategy for colorectal cancer. However, its clinical use is hindered by its low water solubility and bioavailability. A pH/glutathione (GSH) dual-responsive nano-herb delivery system (PMDC NPs) has been developed for the targeted delivery of DHA, accompanied by abundant carbon monoxide (CO) release. Due to the passive enhanced permeability and retention (EPR) effect and active targeting mediated by pHCT74 peptide binding to overexpressed α-enolase on colorectal cancer cells, the pHCT74/MOF-5@DHA&CORM-401 nanoparticles (PMDC NPs) exhibited specific targeting capacity against colorectal cancer cells. Once reaching the tumor site, the pH/GSH dual-responsive behavior of metal-organic framework-5 (MOF-5) enabled the rapid release of cargo, including DHA and CORM-401, in the acidic tumor microenvironment. Subsequently, DHA stimulated CORM-401 to release CO, which facilitated ROS-induced ferroptosis and apoptosis, leading to immunogenic cell death (ICD) and a sustained antitumor response through the release of tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs). Overall, PMDC NPs enhanced the bioavailability of DHA and exhibited outstanding therapeutic effectiveness both in vitro and in vivo, indicating their potential as a promising and feasible alternative for synergistic treatment with immunotherapy and gas therapy in the clinical management of colorectal cancer., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Clinical guidelines for infectious keratitis treatment require that anti-inflammatory drugs can only be used after infection elimination, which causes irreversible inflammatory damage to the cornea. In this work, photodynamic metal organic frameworks (PCN-224) were used as drug carrier to load Pt NPs with catalase-like activity and anti-inflammatory drug (Dexamethasone, DXMS) for endogenous oxygen generation and reduced corneal damage, respectively. The photodynamic therapy (PDT) effect was greatly enhanced in bacteria elimination and bacterial biofilms removal through catalysis of overexpressed hydrogen peroxide (H 2 O 2 , ∼8.0 and 31.0 μM in bacterial solution and biofilms, respectively) into oxygen by Pt NPs. More importantly, the cationic liposome modified PCN-224@Pt@DXMS@Liposomes (PPDL NPs) greatly enhanced the adhesion to negatively charged ocular surface and penetration into corneal barrier and bacterial biofilms. Both in vitro cell viability test and in vivo eye irritation tests proved good biocompatibility of PPDL NPs under 660 nm laser irradiation. Furthermore, PDT of PPDL NPs in rapid bacteria killing was verified through infectious keratitis animal model. The superior bactericidal effect of antibacterial materials could largely replace the bactericidal effect of the immune system. It is worth mentioning that this simultaneous sterilization and anti-inflammation treatment mode is a new exploration against the clinical treatment guidelines., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nitric oxide (NO) is an endogenous gasotransmitter regulating alternative physiological processes in the cardiovascular system. To achieve translational application of NO, continued efforts are made on the development of orally active NO prodrugs for long-term treatment of chronic cardiovascular diseases. Herein, immobilization of NO-delivery [Fe 2 (μ-SCH 2 CH 2 COOH) 2 (NO) 4 ] ( DNIC-2 ) onto MIL-88B, a metal-organic framework (MOF) consisting of biocompatible Fe 3+ and 1,4-benzenedicarboxylate (BDC), was performed to prepare a DNIC@MOF microrod for enhanced oral delivery of NO. In simulated gastric fluid, protonation of the BDC linker in DNIC@MOF initiates its transformation into a DNIC@tMOF microrod, which consisted of DNIC-2 well dispersed and confined within the BDC-based framework. Moreover, subsequent deprotonation of the BDC-based framework in DNIC@tMOF under simulated intestinal conditions promotes the release of DNIC-2 and NO. Of importance, this discovery of transformer-like DNIC@MOF provides a parallel insight into its stepwise transformation into DNIC@tMOF in the stomach followed by subsequent conversion into molecular DNIC-2 in the small intestine and release of NO in the bloodstream of mice. In comparison with acid-sensitive DNIC-2 , oral administration of DNIC@MOF results in a 2.2-fold increase in the oral bioavailability of NO to 65.7% in mice and an effective reduction of systolic blood pressure (SBP) to a ΔSBP of 60.9 ± 4.7 mmHg in spontaneously hypertensive rats for 12 h.

Patches with the capacity of controllable delivering active molecules toward the wound bed to promote wound healing are expectant all along. Herein, a novel porous metal-organic framework (MOF) microneedle (MN) patch enabling photothermal-responsive nitric oxide (NO) delivery for promoting diabetic wound healing is presented. As the NO-loadable copper-benzene-1,3,5-tricarboxylate (HKUST-1) MOF is encapsulated with graphene oxide (GO), the resultant NO@HKUST-1@GO microparticles (NHGs) are imparted with the feature of near-infrared ray (NIR) photothermal response, which facilitate the controlled release of NO molecules. When these NHGs are embedded in a porous PEGDA-MN, the porous structure, larger specific surface area, and sufficient mechanical strength of the integrated MN could promote a more accurate and deeper delivery of NO molecules into the wound site. By applying the resultant NHG-MN to the wound of a type I diabetic rat model, the authors demonstrate that it is capable of accelerating vascularization, tissue regeneration, and collagen deposition, indicating its bright prospect applied in wound healing and other therapeutic scenarios., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: The complex tumor microenvironment and non-targeting drugs limit the efficacy of clinical tumor therapy. For ensuring the accurate delivery and maximal effects of anticancer drugs, it is important to develop innovative drug delivery system based on nano-strategies., Result: In this study, an intracellular acidity-responsive polymeric metal organic framework nanoparticle (denoted as DIMP) has been constructed, which can co-deliver the chemotherapy agent of doxorubicin (DOX) and phototherapy agent of indocyanine green (ICG) for breast carcinoma theranostics. Specifically, DIMP possesses a suitable and stable nanometer size and can respond to the acidic microenvironment in cells, thus precisely delivering drugs into target tumor sites and igniting the biological reactions towards cell apoptosis. Following in vivo and in vitro results showed that DIMP could be effectively accumulated in tumor sites and induced powerful immunogenic cell death (ICD) effect., Conclusion: The designed DIMP displayed its effectiveness in combined photo-chemotherapy with auxiliary of ICD effect under a multimodal imaging monitor. Thus, the present MOF-based strategy may offer a potential paradigm for designing drug-delivery system for image-guided synergistic tumor therapy., (© 2021. The Author(s).)

Polyurethane foams (PUFs) have attracted attention as biomaterials because of their low adhesion to the wound area and suitability as biodegradable or bioactive materials. The composition of the building blocks for PUFs can be controlled with additives, which provide excellent anti-drug resistance and biocompatibility. Herein, nanosized Cu-BTC (copper(II)-benzene-1,3,5-tricarboxylate) was incorporated into a PUF via the crosslinking reaction of castor oil and chitosan with toluene-2,4-diisocyanate, to enhance therapeutic efficiency through the modification of the surface of PUF. The physical and thermal properties of the nanosized Cu-BTC-incorporated PUF (PUF@Cu-BTC), e.g., swelling ratio, phase transition, thermal gravity loss, and cell morphology, were compared with those of the control PUF. The bactericidal activities of PUF@Cu-BTC and control PUF were evaluated against Pseudomonas aeruginosa , Klebsiella pneumoniae , and methicillin-resistant Staphylococcus aureus . PUF@Cu-BTC exhibited selective and significant antibacterial activity toward the tested bacteria and lower cytotoxicity for mouse embryonic fibroblasts compared with the control PUF at a dose of 2 mg mL -1 . The Cu(II) ions release test showed that PUF@Cu-BTC was stable in phosphate buffered saline (PBS) for 24 h. The selective bactericidal activity and low cytotoxicity of PUF@Cu-BTC ensure it is a candidate for therapeutic applications for the drug delivery, treatment of skin disease, and wound healing.

Tuberculosis (TB) is an infectious disease that causes a great number of deaths in the world (1.5 million people per year). This disease is currently treated by administering high doses of various oral anti-TB drugs for prolonged periods (up to 2 years). While this regimen is normally effective when taken as prescribed, many people with TB experience difficulties in complying with their medication schedule. Furthermore, the oral administration of standard anti-TB drugs causes severe side effects and widespread resistances. Recently, we proposed an original platform for pulmonary TB treatment consisting of mannitol microspheres (Ma MS) containing iron (III) trimesate metal-organic framework (MOF) MIL-100 nanoparticles (NPs). In the present work, we loaded this system with the first-line anti-TB drug isoniazid (INH) and evaluated both the viability and safety of the drug vehicle components, as well as the cell internalization of the formulation in alveolar A549 cells. Results show that INH-loaded MOF (INH@MIL-100) NPs were efficiently microencapsulated in Ma MS, which displayed suitable aerodynamic characteristics for pulmonary administration and non-toxicity. MIL-100 and INH@MIL-100 NPs were efficiently internalized by A549 cells, mainly localized in the cytoplasm. In conclusion, the proposed micro-nanosystem is a good candidate for the pulmonary administration of anti-TB drugs.

Introduction: The development of multidrug resistance (MDR) is a major cause for the failure of chemotherapy, which requires the aid of nanomedicine., Methods: Here in our study, a Cu 2+ based metal-organic framework (COF) was firstly developed and employed as a carrier for the delivery of glucose oxidase (GOx) and doxorubicin (Dox) (COF/GOx/Dox) for the therapy of MDR lung cancers., Results: Our results showed that the GOx can catalyze glucose and produce H 2 O 2 . In the mean time, the Cu 2+ can react with GSH and then transform into Cu + , which resulted in GSH depletion. Afterwards, the produced Cu + and H 2 O 2 trigger Fenton reaction to generate ROS to damage the redox equilibrium of cancer cells. Both effects contributed to the reverse of MDR in A549/Dox cells and finally resulted in significantly enhanced in vitro/in vivo anticancer performance., Discussion: The combination of glutathione depletion/reactive oxygen species elevation might be a promising strategy to enhance the efficacy of chemotherapy and reverse MDR in cancers., (Copyright © 2021. Published by Elsevier Masson SAS.)

Owing to their facile synthesis, tailorable porosity, diverse compositions, and low toxicity, zeolitic imidazolate framework (ZIF) nanoparticles (NPs) have emerged as attractive platforms for a variety of biologically relevant applications. To date, a small subset of ZIFs representing only two topologies and very few linker chemistries have been studied in this realm. We seek to expand the bio-design space for ZIF NPs through the targeted synthesis of a hierarchically complex ZIF based on two types of cages, ZIF-20, with lta topology. This study demonstrates the rapid synthesis and size tunability of ZIF-20 particles across the micro and nanoregimes via microwave heating and the use of a modulating agent. To evaluate the utility of ZIF particles for biological applications, we examine their stability in biologically relevant media and demonstrate biocompatibility with A549 human epithelial cells. Further, the ability to encapsulate and release methylene blue, a therapeutic and bioimaging agent, is validated. Importantly, ZIF-20 NPs display a unique behavior relative to previously studied ZIFs based on their specific structural and chemical features. This finding highlights the need to expand the design space across the broader ZIFs family, to exploit a wider range of relevant properties for biological applications and beyond.

Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H 2 S) are gaseous signaling molecules (gasotransmitters) that regulate both physiological and pathological processes and offer therapeutic potential for the treatment of many diseases, such as cancer, cardiovascular disease, renal disease, bacterial and viral infections. However, the inherent labile nature of therapeutic gases results in difficulties in direct gases administration and their controlled delivery at clinically relevant ranges. Metal-organic frameworks (MOFs) with highly porous, stable, and easy-to-tailor properties have shown promising therapeutic gas delivery potential. Herein, we highlight the recent advances of MOF-based platforms for therapeutic gas delivery, either by endogenous (i.e., direct transfer of gases to targets) or exogenous (i.e., stimulating triggered release of gases) means. Reports that involve in vitro and/or in vivo studies are highlighted due to their high potential for clinical translation. Current challenges for clinical requirements and possible future innovative designs to meet variable healthcare needs are discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Chemotherapeutic agents used in treating certain cancer types operate in a non-selective manner tending to accumulate in normal, healthy tissue when high doses are used. To mitigate the toxicity effect resulting from this, there is an urgent need to develop active nano delivery systems capable of regulating optimal doses specifically to cancer cells without harming adjacent normal cells. Herein, we report a versatile nanoparticle - zeolitic imidazolate framework-8 (nZIF-8) - that is loaded with a chemotherapeutic agent (gemcitabine; GEM) and surface-functionalized with an autonomous homing system (Arg-Gly-Asp peptide ligand; RGD) via a straightforward, one-pot solvothermal reaction. Successful functionalization of the surface of nZIF-8 loaded GEM (GEM⊂nZIF-8) with RGD was proven by spectroscopic and electron microscopy techniques. This surface-functionalized nanoparticle (GEM⊂RGD@nZIF-8) exhibited enhanced uptake in human lung cancer cells (A549), compared with non-functionalized GEM⊂nZIF-8. The GEM⊂RGD@nZIF-8, experienced not only efficient uptake within A549, but also induced obvious cytotoxicity (75% at a concentration of 10 μg mL-1) and apoptosis (62%) after 48 h treatment when compared to the nanoparticle absent of the RGD homing system (GEM⊂nZIF-8). Most importantly, this surface-functionalized nanoparticle was more selective towards lung cancer cells (A549) than normal human lung fibroblast cells (MRC-5) with a selectivity index (SI) of 3.98. This work demonstrates a new one-pot strategy for realizing a surface-functionalized zeolitic imidazolate framework that actively targets cancer cells via an autonomous homing peptide system to deliver a chemotherapeutic payload effectively.

Nano metal organic frameworks (NMOFs) belong to the group of nanoporous materials. Over the decades, the conducted researches explored the area for the potential applications of NMOFs in areas like biomedical, chemical engineering and materials science. Recently, NMOFs have been explored for their potential use in cancer diagnosis and therapeutics. The excellent physico-chemical features of NMOFs also make them a potential candiadate to facilitate drug design, delivery and storage against cancer cells. In this review, we have explored the characterstic features, synthesis methods, NMOFs based drug delivery, diagnosis and imaging in various cancer types. In addition to this, we have also pondered on the stability and toxicological concerns of NMOFs. Despite, a significant research has been done for the potential use of NMOFs in cancer diagonostic and therapeutics, more information regarding the stability, in-vivo clearance, toxicology, and pharmacokinetics is still needed to ehnace the use of NMOFs in cancer diagonostic and therapeutics., (Copyright © 2019. Published by Elsevier Ltd.)

The coordination polymer CPO-27-Mg was rapidly synthesized under microwave irradiation. This material exhibits a sufficiently high drug loading towards aspirin (~8% wt.) and paracetamol (~14% wt.). The binding of these two molecules with the inner surface of the metal-organic framework was studied employing the Gaussian and Plane Wave approach of the Density Functional Theory. The structure of CPO-27-Mg persists after the adsorption of aspirin or paracetamol and their desorption energies, being quite high, decrease under solvent conditions.

Oral administration of medicine faces physiological constraints imposed by the gastrointestinal tract (GIT) and simultaneously causes irritation to GI mucosa, which motivates us to pursue the innovation of a GI drug delivery system. Inspired by the mucosa-nutrient functions of Zinc element and smectite clay, a montmorillonite (MMT)-enveloped zeolitic imidazolate framework (M-ZIF-8) is developed in a successive one-pot fabrication of ZIF-8 encapsulated medicine, and followed MMT coating to yield a core-shell nanoplatform for GI drug delivery. ZIF-8 encapsulated medicines can maintain their intrinsic structure, and MMT layer potentiates mucous-adhesion and optimizes medicine release. Validated in gastritis and colitis models, M-ZIF-8 not only achieves efficient GI delivery of nonsteroidal anti-inflammatory drugs (NSAIDs) for inflammation inhibition, but also reduces the NSAIDs-induced GI irritation, promoting mucosal healing in GIT. Coupled with the facile construction and biocompatibility, M-ZIF-8 shows a significant advancement in GI drug delivery.

Although nanoscaled metal-organic frameworks (nanoMOFs) are promising drug carriers, their appropriate formulation remains almost unexplored and basically restricted to intravenous routes. Lungs, beneficiating from a large absorption surface and low enzymatic presence, are a very attractive target for both local and systemic delivery. However, pulmonary nanoMOF formulation is a pending and defying task. Thus, we propose a pioneer nanoMOF-based microsphere system as a potential platform for pulmonary administration. A biocompatible nanoMOF was successfully encapsulated in mannitol by a simple and continuous spray-drying technique. Upon intratracheal administration to rats, the resulting formulation, exhibiting optimal properties ( i.e ., homogeneity, size, density, and spray-drying process yield), was able to release the intact nanoMOF carrier uniformly along the lungs, reaching the bronchioles and alveoli.

Oral insulin delivery has revolutionized diabetes treatment, but challenges including degradation in the gastrointestinal environment and low permeation across the intestinal epithelium remain. Herein, to overcome these barriers, we developed a novel biodegradable nanocomposite microsphere embedded with metal-organic framework (MOF) nanoparticles. An iron-based MOF nanoparticle (NP) (MIL-100) was first synthesized as a carrier with an insulin loading capacity of 35%. The insulin-loaded MIL-100 nanoparticles modified with sodium dodecyl sulfate (Ins@MIL100/SDS) promoted insulin permeation across Caco-2 monolayer models in vitro. To improve resistance to the gastric acid environment, Ins@MIL100/SDS nanoparticles were embedded into a biodegradable microsphere to construct the nanocomposite delivery system (Ins@MIL100/SDS@MS). The microspheres effectively protected the MOF NPs from rapid degradation under acidic conditions and could release insulin-loaded MOF NPs in the simulated intestinal fluid. After the oral administration of Ins@MIL100/SDS@MS into BALB/c nude mice, increased intestinal absorption of the insulin was detected compared to the oral administration of free insulin or Ins@MIL100/SDS. Furthermore, significantly enhanced plasma insulin levels were obtained for over 6 h after oral administration of Ins@MIL100/SDS@MS into diabetic rats, leading to a remarkably enhanced effect in lowering blood glucose level with a relative pharmacological availability of 7.8%. Thus, the MOF-nanoparticle-incorporated microsphere may provide a new strategy for effective oral protein delivery.

We design multifunctional CDDP-VPA@ZrMOF-Cys-PEG nanoparticles (CVZP NPs) based on the properties of valproic acid (VPA) that can downregulate the expression of vascular endothelial growth factor (VEGF) to reduce the drug resistance of tumor cells. In vivo experiments confirm that chemotherapy combined with microwave thermal therapy (MWTT) can significantly improve the therapeutic effect of cisplatin-resistant lung cancer.

Coordinative interactions between multivalent metal ions and drug derivatives with Lewis base functions give rise to nanoscale coordination polymers (NCPs) as delivery systems. As the pharmacologically active agent constitutes a main building block of the nanomaterial, the resulting drug loadings are typically very high. By additionally selecting metal ions with favorable pharmacological or physicochemical properties, the obtained NCPs are predominantly composed of active components which serve individual purposes, such as pharmacotherapy, photosensitization, multimodal imaging, chemodynamic therapy or radiosensitization. By this approach, the assembly of drug molecules into NCPs modulates pharmacokinetics, combines pharmacological drug action with specific characteristics of metal components and provides a strategy to generate tailorable multifunctional nanoparticles. This article reviews different applications and recent examples of such highly functional nanopharmaceuticals with a high 'material economy'. Lay Summary: Nanoparticles, that are small enough to circulate in the bloodstream and can carry cargo molecules, such as drugs, imaging or contrast agents, are attractive materials for pharmaceutical applications. A high loading capacity is a generally aspired parameter of nanopharmaceuticals to minimize patient exposure to unnecessary nanomaterial. Pharmaceutical agents containing Lewis base functions in their molecular structure can directly be assembled into metal-organic nanopharmaceuticals by coordinative interaction with metal ions. Such coordination polymers generally feature extraordinarily high loading capacities and the flexibility to encapsulate different agents for a simultaneous delivery in combination therapy or 'theranostic' applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Photoreceptor degeneration is one of the most refractory oculopathy in the world, leading to vision loss in severe cases. Methyprednisolone is one of the most commonly prescribed medications for the treatment of retinal degenerative diseases, either by oral administration or repeated intraocular injections. However, the efficacy was unsatisfactory due to its systemic or local side effects and short retention time within the retina., Methods: Nanoscale zirconium-porphyrin metal-organic framework (NPMOF) was synthesized and characterized. The biotoxicity and imaging capability of NPMOF were evaluated using zebrafish embryos and larvae. NPMOF was then used as a skeleton and loaded with methylprednisolone (MPS) to prepare a novel kind of nanoparticle, MPS-NPMOF. Photoreceptor degeneration was induced by high-intensity light exposure in adult zebrafish. MPS-NPMOF was delivered to the injured retina by intraocular injection. The photoreceptor regeneration and its underlying mechanism were explored by immunohistochemistry, quantitative real-time polymerase chain reaction and behavioral test., Results: NPMOF not only had low biotoxicity but also emitted bright fluorescence. Following a single MPS-NPMOF intraocular injection, the injured retina exhibited the faster photoreceptor regeneration with better visual function by promoting the cell proliferation., Conclusion: NPMOF is an ideal carrier and could be applied in tracking and delivering medications. By intraocular injection, the novel drug delivery system, MPS-NPMOF, accomplishes the sustained release of drug and plays a therapeutic role in photoreceptor degeneration., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Wang et al.)

Uniform micron sized hierarchical COF (HCOF) spheres were fabricated by a template-free solution-based aging method at room temperature for the first time. The postsynthetic metalation of HCOF with Fe3+ makes the metalated HCOF an excellent photothermal agent (PTA) for photothermal therapy (PTT).

The application of photothermal therapy to treat bacterial infections remains a challenge, as the high temperatures required for bacterial elimination can damage healthy tissues. Here, we develop an exogenous antibacterial agent consisting of zinc-doped Prussian blue (ZnPB) that kills methicillin-resistant Staphylococcus aureus in vitro and in a rat model of cutaneous wound infection. Local heat triggered by the photothermal effect accelerates the release and penetration of ions into the bacteria, resulting in alteration of intracellular metabolic pathways and bacterial killing without systemic toxicity. ZnPB treatment leads to the upregulation of genes involved in tissue remodeling, promotes collagen deposition and enhances wound repair. The efficient photothermal conversion of ZnPB allows the use of relatively few doses and low laser flux, making the platform a potential alternative to current antibiotic therapies against bacterial wound infections.

Since current subunit vaccines are limited by a short half-life in vivo and weak immune responses when used alone without adjuvants, there is an unmet need for combing carriers with complement activation signals to interrupt outbreaks in real-time. Amino-functionalized zirconium-based MOFs (UiO-AM) could activate the complement system, which plays an important role in innate and adaptive immunity. Our data provide design principles for studies on complement activation as a safe vaccine carrier that can effectively enhance immune responses against antigens in vivo.

Targeted activation or enhancement is an attractive strategy in the design of nano-theranostics. However, the responsiveness of the nanoagents is restricted by the limited levels of intra-tumor stimuli. Herein, we constructed a positive feedback nanoamplifier by encapsulating glucose oxidase (GOx) in the ferric ions contained metal organic framework (MIL-100), and coating the nanoparticles with polydopamine modified hyaluronic acid (HA-PDA). The mechanism of action of the ensuing nanoamplifiers was three pronged: 1) the high intra-tumor acidity accelerated the release of GOx, which consumed endogenous glucose and "starved" the tumors, in addition to aggravating the local acidity and H 2 O 2 levels; 2) the hydroxyl radicals (·OH) generated from the Fenton-like reaction between MIL-100 with H 2 O 2 contributed to the chemodynamic tumor therapy and augmented the O 2 microenvironment, which could be speeded up under acid condition; 3) the oxygen (O 2 ) produced in the Fenton-like reaction relieved the intra-tumor hypoxia and ensured the enzymatic reaction of GOx, along with augmenting the photoacoustic signal of nanoamplifier. Preliminary experiments in tumor bearing mice showed that the nanoamplifier not only boosted the local acidity/H 2 O 2 /O 2 levels in tumor site to successfully suppress the growth of tumors through the self-enhanced chemodynamic/starving therapy, but also achieved the photoacoustic imaging of tumors. Taken together, this novel nanoamplifier with the abilities of self-enhanced tumor imaging and therapy is a promising entrant in the field of anti-tumor theranostics., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Cancer cells are susceptible to oxidative stress; therefore, selective elevation of intracellular reactive oxygen species (ROS) is considered as an effective antitumor treatment. Here, a liposomal formulation of dichloroacetic acid (DCA) and metal-organic framework (MOF)-Fe 2+ (MD@Lip) has been developed, which can efficiently stimulate ROS-mediated cancer cell apoptosis in vitro and in vivo. MD@Lip can not only improve aqueous solubility of octahedral MOF-Fe 2+ , but also generate an acidic microenvironment to activate a MOF-Fe 2+ -based Fenton reaction. Importantly, MD@Lip promotes DCA-mediated mitochondrial aerobic oxidation to increase intracellular hydrogen peroxide (H 2 O 2 ), which can be consequently converted to highly cytotoxic hydroxyl radicals (•OH) via MOF-Fe 2+ , leading to amplification of cancer cell apoptosis. Particularly, MD@Lip can selectively accumulate in tumors, and efficiently inhibit tumor growth with minimal systemic adverse effects. Therefore, liposome-based combination therapy of DCA and MOF-Fe 2+ provides a promising oxidative stress-associated antitumor strategy for the management of malignant tumors., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Cancer treatment using functional proteins, DNA/RNA, or complex bio-entities is important in both preclinical and clinical studies. With the help of nano-delivery systems, these biomacromolecules can enrich cancer tissues to match the clinical requirements. Biomineralization via a self-assembly process has been widely applied to provide biomacromolecules exoskeletal-like protection for immune shielding and preservation of bioactivity. Advanced metal-organic framework nanoparticles (MOFs) are excellent supporting matrices due to the low toxicity of polycarboxylic acids and metals, high encapsulation efficiency, and moderate synthetic conditions. In this review, we study MOFs-based biomineralization for cancer treatment and summarize the unique properties of MOF hybrids. We also evaluate the outlook of potential cancer treatment applications for MOFs-based biomineralization. This strategy likely opens new research orientations for cancer theranostics., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Polyphenols, due to their high biocompatibility and wide occurrence in nature, have attracted increasing attention in the engineering of functional materials ranging from films, particles, to bulk hydrogels. Colloidal particles, such as nanogels, hollow capsules, mesoporous particles and core-shell structures, have been fabricated from polyphenols or their derivatives with a series of polymeric or biomolecular compounds through various covalent and non-covalent interactions. These particles can be designed with specific properties or functionalities, including multi-responsiveness, radical scavenging capabilities, and targeting abilities. Moreover, a range of cargos (e.g., imaging agents, anticancer drugs, therapeutic peptides or proteins, and nucleic acid fragments) can be incorporated into these particles. These cargo-loaded carriers have shown their advantages in the diagnosis and treatment of diseases, especially of cancer. In this review, we summarize the assembly of polyphenol-based particles, including polydopamine (PDA) particles, metal-phenolic network (MPN)-based particles, and polymer-phenol particles, and their potential biomedical applications in various diagnostic and therapeutic applications., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

The biomedical application of discrete supramolecular metal-based structures, including supramolecular coordination complexes (SCCs), is still an emergent field of study. However, pioneering studies over the last 10 years demonstrated the potential of these supramolecular compounds as novel anticancer drugs, endowed with different mechanisms of action compared to classical small-molecules, often related to their peculiar molecular recognition properties. In addition, the robustness and modular composition of supramolecular metal-based structures allows for an incorporation of different functionalities in the same system to enable imaging in cells via different modalities, but also active tumor targeting and stimuli-responsiveness. Although most of the studies reported so far exploit these systems for therapy, supramolecular metal-based structures may also constitute ideal scaffolds to develop multimodal theranostic agents. Of note, the host-guest chemistry of 3D self-assembled supramolecular structures - within the metallacages family - can also be exploited to design novel drug delivery systems for anticancer chemotherapeutics. In this review, we aim at summarizing the pivotal concepts in this fascinating research area, starting with the main design principles and illustrating representative examples while providing a critical discussion of the state-of-the-art. A section is also included on supramolecular organometallic complexes (SOCs) whereby the (organic) linker is forming the organometallic bond to the metal node, whose biological applications are still to be explored. Certainly, the myriad of possible supramolecular metal-based structures and their almost limitless modularity and tunability suggests that the biomedical applications of such complex chemical entities will continue along this already promising path., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Metal-organic frameworks (MOFs) have high surface area, tunable pore size, and high loading capacity, making them promising for drug delivery. However, their synthesis requires organic solvents, high temperature and high pressure that are incompatible with biomacromolecules. Zeolitic imidazole frameworks (ZIF-8) which forms through coordination between zinc ions and 2-methylimidazole (MeIM) have emerged as an advanced functional material for drug delivery due to its unique features such as high loading and pH-sensitive degradation. In this study, we took advantage of a natural biomineralization process to create aluminum-containing nanoZIF-8 particles for antigen delivery. Without organic solvents or stabilizing agent, nanoparticles (ZANPs) were synthesized by a mild and facile method with aluminum, model antigen ovalbumin (OVA) and ZIF-8 integrated. A high antigen loading capacity (%) of 30.6% and a pH dependent antigen release were achieved. A Toll-like receptor 9 agonist cytosine-phosphate-guanine oligodeoxynucleotides (CpG) was adsorbed on the surface of ZANPs (hereafter CpG/ZANPs) to boost the immune response. After subcutaneous injection in vivo, CpG/ZANPs targeted lymph nodes (LNs), where their cargo was efficiently internalized by LN-resident antigen-presenting cells (APCs). ZANPs decomposition in lysosomes released antigen into the cytoplasm and enhanced cross-presentation. Moreover, CpG/ZANPs induced strong antigen-specific humoral and cytotoxic T lymphocyte responses that significantly inhibited the growth of EG7-OVA tumors while showing minimal cytotoxicity. We demonstrate that ZANPs may be a safe and effective vehicle for the development of cancer vaccines., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The design of hybrid metal-organic framework (MOF) nanomaterials by integrating inorganic nanoparticle into MOF (NP@MOF) has demonstrated outstanding potential for obtaining enhanced, collective, and extended novel physiochemical properties. However, the reverse structure of MOF-integrated inorganic nanoparticle (MOF@NP) with multifunction has rarely been reported. Methods : We developed a facile in-situ growth method to integrate MOF nanoparticle into inorganic nanomaterial and designed a fluorescence switch to trigger enhanced photodynamic therapy. The influence of "switch" on the photodynamic activity was studied in vitro . The in vivo mice with tumor model was applied to evaluate the "switch"-triggered enhanced photodynamic therapy efficacy. Results : A core-satellites structure with fluorescence off and on function was obtained when growing MnO 2 on the surface of fluorescent zeolitic imidazolate framework (ZIF-8) nanoparticles. Furthermore, A core-shell structure with photodynamic activity off and on function was achieved by growing MnO 2 on the surface of porphyrinic ZrMOF nanoparticles (ZrMOF@MnO 2 ). Both the fluorescence and photodynamic activities can be turned off by MnO 2 and turned on by GSH. The GSH-responsive activation of photodynamic activity of ZrMOF@MnO 2 significantly depleted the intracellular GSH via a MnO 2 reduction reaction, thus triggering an enhanced photodynamic therapy efficacy. Finally, the GSH-reduced Mn 2+ provided a platform for magnetic resonance imaging-guided tumor therapy. Conclusion : This work highlights the impact of inorganic nanomaterial on the MOF properties and provides insight to the rational design of multifunctional MOF-inorganic nanomaterial complexes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Metal-organic frameworks (MOFs) have been applied in chemotherapeutic drug loading for cancer treatment, but challenging for cases with large and malignant lesions. To overcome these difficulties, combinational therapies of chemotherapy and photothermal therapy (PTT) with potentially high selectivity and slight aggressiveness have drawn tremendous attention to treat various tumors. However, current MOF-based nanohybrids with photothermal agents involve tedious synthesis processes and heterogeneous structures. Herein, we employ MIL-53 as a microreactor to grow polypyrrole (PPy) nanoparticles in situ for the fabrication of PPy@MIL-53 nanocomposites. Fe 3+ in MIL-53, as an intrinsic oxidizing agent, can oxidize the pyrrole monomer to generate PPy nanoparticles. The prepared PPy@MIL-53 nanocomposites integrate the intrinsic advantages of MOFs with high drug loading ability and magnetic resonance imaging (MRI) capacity, and PPy nanoparticles with outstanding PTT ability and excellent biocompatibility. The versatile PPy@MIL-53 nanocomposites with multiple functions displayed in vitro and in vivo synergism of photothermal-chemotherapy for cancer, potentially MRI-guided. The proposed MOF microreactor-based synthesis strategy shows a promising prospect in the fabrication of diverse multifunctional nanohybrids for tumor theranostics in vivo.

A zeolitic imidazolate framework (ZIF-8) with high loading capacity and pH-responsive properties, an important subclass of metal-organic frameworks (MOFs), has become a promising material for drug delivery. A multifunctional drug delivery system (DDS) was designed in this work for effective targeting delivery of chloroquine diphosphate (CQ) as an autophagy inhibitor. The ZIF-8 nanoparticles encapsulating CQ (CQ@ZIF-8 NPs) were fabricated by a simple one-pot method and were then decorated with methoxy poly(ethylene glycol)-folate (FA-PEG), a special identifier of cancer cells, to form FA-PEG/CQ@ZIF-8. The target identification of FA-PEG/CQ@ZIF-8 NPs, compared with CQ@ZIF-8 NPs, leads to an increasing number of NPs being internalized into HeLa cells, which decreases the loss of drugs and results in high cytotoxicity of CQ for cancer cells. The lower viabilities of HeLa cells (cancer cells) and higher viabilities of HEK293 cells (healthy cells) treated with FA-PEG/CQ@ZIF-8 NPs show that the special target for cancer cells results from the combinations of folic acid and folate receptors on the surface of HeLa cells. The quantitative measurements of autophagy-related proteins and the detection of autophagy flux in HeLa cells suggest that the autophagosome formation and autophagy flux are appreciably blocked after the cells are treated with FA-PEG/CQ@ZIF-8 NPs. The ZIF-8 can disintegrate only under low pH conditions, resulting in fast and full release of CQ. The pH-responsive and tumor-targeted properties of the NPs can control the drug release and enhance the efficiency of autophagy inhibition. It indicates that the FA-PEG/CQ@ZIF-8 NPs combining target identification with controlled drug release can be used as a novel model for discussing targeted cancer therapy and inhibiting the autophagy of cancer cells.

Poisoning and accidental oral intoxication are major health problems worldwide. Considering the insufficient efficacy of the currently available detoxification treatments, a pioneering oral detoxifying adsorbent agent based on a single biocompatible metal-organic framework (MOF) is here proposed for the efficient decontamination of drugs commonly implicated in accidental or voluntary poisoning. Furthermore, the in vivo toxicity and biodistribution of a MOF via oral administration have been investigated for the first time. Orally administered upon a salicylate overdose, this MOF is able to reduce the salicylate gastrointestinal absorption and toxicity more than 40-fold (avoiding histological damage) while exhibiting exceptional gastrointestinal stability (<9% degradation), poor intestinal permeation, and safety.

We have synthesized a core@shell nanocomposite using biocompatible bovine serum albumin (BSA) as the core and a pH-sensitive metal-organic framework (MOF) as the shell. Doxorubicin (DOX)/BSA nanoparticles as cores have been prepared. A zeolitic imidazolate framework-8 (ZIF-8) layer has been coated on the outer surface of the DOX/BSA core. The ZIF layer acts as a capsule for the safe storage of DOX under physiological conditions. An efficient pH-responsive drug delivery system using a BSA/DOX@ZIF, in which the drug is not released in PBS at pH 7.4 but is released at low pH (5.0-6.0), has been constructed. Compared to the pure ZIF, a better biocompatibility has been obtained using the BSA/DOX@ZIF. The BSA/DOX@ZIF shows a much higher efficacy than free DOX against the breast cancer cell line MCF-7. The positive charges on the outer surface of the BSA/DOX@ZIF also improve its cellular uptake.

Photodynamic therapy (PDT) has been applied in clinical cancer treatment. Here we report an aptamer-functionalized nanoscale metal-organic framework for targeted PDT. Our nanosystem can be easily prepared and successfully used for targeted PDT with a significantly enhanced therapeutic efficacy in vitro and in vivo . Methods: By combining the strong binding ability between phosphate-terminated aptamers and Zr-based nanoscale metal-organic frameworks (Zr-NMOFs) and the intercalation of photosensitizer TMPyP4 within the G-quadruplex DNA structure, TMPyP4-G4-aptamer-NMOFs were prepared. The characteristics and photodynamic performance of TMPyP4-G4-aptamer-NMOFs were examined after preparation. Then, we studied their stability, specific recognition ability, and phototoxicity in vitro . For in vivo experiments, the nanosystem was intratumorally injected into a HeLa subcutaneous xenograft tumor mouse model. After irradiation on day 0, mice were further injected with the nanosystem on day 5 and were again subjected to laser irradiation for 30 min. Tumor volumes and body weights of all mice were measured by caliper every 2 days after the treatment. Results: The nanosystem induced 90% cell death of targeted cells. In contrast, the control cells maintained about 40% cell viability at the same concentration of nanosystem. For the in vivo experiments, the nanosystem-treated group maintained more than 76% inhibition within the entire experimental period. Conclusion: We have demonstrated that our smart TMPyP4-G4-sgc8-NMOFs nanosystem can be used for targeted cancer therapy with high efficiency., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

The development of effective therapies to control methicillin-resistant Staphylococcus aureus (MRSA) infections is challenging because antibiotics can be degraded by the production of certain enzymes, for example, β-lactamases. Additionally, the antibiotics themselves fail to penetrate the full depth of biofilms formed from extracellular polymers. Nanoparticle-based carriers can deliver antibiotics with better biofilm penetration, thus combating bacterial resistance. In this study, we describe a general approach for the construction of β-lactam antibiotics and β-lactamase inhibitors co-delivery of nanoantibiotics based on metal-carbenicillin framework-coated mesoporous silica nanoparticles (MSN) to overcome MRSA. Carbenicillin, a β-lactam antibiotic, was used as an organic ligand that coordinates with Fe 3+ to form a metal-carbenicillin framework to block the pores of the MSN. Furthermore, these β-lactamase inhibitor-loaded nanoantibiotics were stable under physiological conditions and could synchronously release antibiotic molecules and inhibitors at the bacterial infection site to achieve a better elimination of antibiotic resistant bacterial strains and biofilms. We confirmed that these β-lactamase inhibitor-loaded nanoantibiotics had better penetration depth into biofilms and an obvious effect on the inhibition of MRSA both in vitro and in vivo., (Copyright © 2017. Published by Elsevier Ltd.)

Bone is the most common organ affected by metastatic breast cancer. Targeting cancers within the bone remains a great challenge due to the inefficient delivery of therapeutic to bone. In this study, a polyethylene glycol (PEG) coated nanoparticles (NPs) made of a Zn 2+ coordination polymer was linked with a bone seeking moiety, alendronate (ALN), to deliver cisplatin prodrug (DSP) to the bone. The particle sizes of this novel system, DSP-Zn@PEG-ALN NPs, were regulated by adjusting the volume ratio of water phase to oil phase in microemulsion. It was small enough (about 55nm) to extravasate through the clefts (80nm) of the bone's sinusoidal capillaries and localize into metastatic bones. DSP-Zn@PEG-ALN NPs showed much higher affinity for hydroxyapatite in vitro and bone in vivo than non-targeted DSP-Zn@PEG NPs and cisplatin. In addition, the in vivo biodistribution studies demonstrated that about 4-fold of platinum was delivered to the bone metastatic lesions than that in healthy bones by DSP-Zn@PEG-ALN NPs intravenously. Finally, DSP-Zn@PEG-ALN NPs not only inhibited the tumor growth efficiently but also reduced the osteocalastic bone destruction. Besides, DSP-Zn@PEG-ALN NPs showed significantly reduced toxicity of cisplatin. These results indicate that the DSP-Zn@PEG-ALN NPs have a great potential in enhancing chemotherapeutic efficacy for the treatment of bone metastatic breast cancer., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Metal organic frameworks (MOFs) have attracted more attention in the last decade because of a suitable pore size, large surface area, and high pore volume. Developing biocompatible MOFs such as the MIL family as a drug delivery system is possible., Purpose: Flurbiprofen (FBP), a nonsteroidal anti-inflammatory agent, is practically insoluble in aqueous solution, and, therefore, needs suitable drug delivery systems. Different biocompatible MOFs such as Ca-MOF and Fe-MILs (53, 100, and 101) were synthesized and employed for FBP delivery., Patients and Methods: A sample of 50 mg of each MOF was mixed and stirred for 24 h with 10 mL of 5 mg FBP in acetonitrile (40%) in a sealed container. The supernatant of the mixture after centrifuging was analyzed by high-performance liquid chromatography to determine the loaded quantity of FBP on the MOF. The overnight-dried solid material after centrifuging the mixture was analyzed for loading percent using X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, nuclear magnetic resonance, and FBP release profile., Results: The loading values of FBP were achieved at 10.0%±1%, 20%±0.8%, 37%±2.3%, and 46%±3.1% on Ca-MOF, Fe-MIL-53, Fe-MIL-101, and Fe-MIL-100, respectively. The FBP release profiles were investigated in a phosphate buffer solution at pH 7.4. The total release of the FBP after 2 days was obtained at 72.9, 75.2, 78.3, and 90.3% for Ca-MOF, Fe-MIL-100, Fe-MIL-53, and Fe-MIL-101, respectively., Conclusion: The MOFs are shown to be a promising drug delivery option for FBP with a significant loading percent and relatively prolonged drug release., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Tumor-associated antigens (TAAs)-loaded nanoparticles are able to be actively internalized by antigen-presenting cells (APCs) and have shown promising potential in cancer immunotherapy. However, current TAAs delivery strategy exhibits limitations of complicated synthesis process, low loading efficiency and inefficient CD8 + cytotoxic T lymphocyte activation leading to unsatisfactory therapeutic effect. Thus, the construction of novel TAAs-delivery systems for enhanced cancer therapy is highly desirable. In this work, we fabricated a very simple yet powerful antigens-delivery system for cancer immunotherapy based-on pH-responsive metal-organic frameworks (MOFs) with size about 30 nm. TAAs can be loaded into MOFs in the one-pot synthesis process and released with the degradation of MOFs in the acidic environment of endo/lysosome as the result of relatively labile metal-ligand bonds. The endosomolytic nanoparticles would facilitate protein antigens escape from endo/lysosome and optimal for enhancing antigen cross-presentation. Furthermore, the introduction of immunostimulatory unmethylated cytosine-phosphate-guanine oligonucleotide (CpG) through Watson-Crick base pairing would further enhance CD8 + cytotoxic T lymphocyte responses. We demonstrated that the method to co-delivery antigens and immunostimulatory molecules was very simple, convenient and effective and showed no obvious toxicity both in vitro and in vivo. This method gave a high antigens-loading capacity and the maximal antigen encapsulating efficiency was about 55% (w/w). Additionally, the pH-responsive co-delivery system exerted enhanced antitumor outcome (about 100% survival) in B16-OVA melanoma cancers in vivo. Furthermore, we confirmed that this high rating of therapeutic effect was attributed to the recruitment of tumor-killing immunocyte. This work demonstrates the ability of pH-responsive, endosomolytic MOFs to induce strong cellular immune responses for cancer therapy by co-delivery of CpG ODN and antigens., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Discovering advanced materials for regulating cell death is of great importance in the development of anticancer therapy. Herein, by harnessing the recently discovered oxidative stress regulation ability of p53 and the Fenton reaction inducing capability of metal-organic network (MON), MON encapsulated with p53 plasmid (MON-p53) was designed to eradicate cancer cells via ferroptosis/apoptosis hybrid pathway. After confirming the detailed mechanism of MON-p53 in evoking ferroptosis, we further discovered that MON-p53 mediated a "bystander effect" to further sensitize cancer cells toward the MON-p53 induced ferroptosis. A 75-day anticancer experiment indicated that MON-p53 treatment not only suppressed the tumor growth but also prolonged the life-span of tumor bearing mice. Owing to its ability to promote intracellular oxidative stress, MON-p53 decreased the blood metastasis, lung metastasis, and liver metastasis. As a consequence, discovering methods to induce cell ferroptosis would provide a new insight in designing anticancer materials.

The growing resistance of pathogens to conventional antibiotics has become a public health problem and raises the need to seek new effective solutions. Metal-organic frameworks (MOFs) are porous, hybrid materials comprising metal ions linked by organic binding ligands. The possibility of using a variety of chemical building components in MOFs enables the formation of structures with desired properties. They can act as a reservoir of metal ions, providing their gradual release and resulting in a sustained antibacterial action analogous to that proposed for metal/metal oxide nanoparticles (NPs) but different to that of antibiotics. These features make MOFs promising candidates for pharmaceutical and biomedical applications, as illustrated by examples discussed in this review., (Copyright © 2016 Elsevier Ltd. All rights reserved.)