Sono-Triggered Cascade Lactate Depletion by Semiconducting Polymer Nanoreactors for Cuproptosis-Immunotherapy of Pancreatic Cancer.

The high level of lactate in tumor microenvironment not only promotes tumor development and metastasis, but also induces immune escape, which often leads to failures of various tumor therapy strategies. We here report a sono-triggered cascade lactate depletion strategy by using semiconducting polymer nanoreactors (SPNLCu) for cancer cuproptosis-immunotherapy. The SPNLCu mainly contain a semiconducting polymer as sonosensitizer, lactate oxidase (LOx) conjugated via a reactive oxygen species (ROS)-cleavable linker and chelated Cu2+. Upon ultrasound (US) irradiation, the semiconducting polymer generates singlet oxygen (1O2) to cut ROS-cleavable linker to allow the release of LOx that catalyzes lactate depletion to produce hydrogen peroxide (H2O2). The Cu2+ will be reduced to Cu+ in tumor microenvironment, which reacts with the produced H2O2 to obtain hydroxyl radical (⋅OH) that further improves LOx release via destroying ROS-cleavable linkers. As such, sono-triggered cascade release of LOx achieves effective lactate depletion, thus relieving immunosuppressive roles of lactate. Moreover, the toxic Cu+ induces cuproptosis to cause immunogenic cell death (ICD) for activating antitumor immunological effect. SPNLCu are used to treat both subcutaneous and deep-tissue orthotopic pancreatic cancer with observably enhanced efficacy in restricting the tumor growths. This study thus provides a precise and effective lactate depletion tactic for cancer therapy.

Biomimetic Dual-Target Theranostic Nanovaccine Enables Magnetic Resonance Imaging and Chemo/Chemodynamic/Immune Therapy of Glioma.

Development of theranostic nanomedicines to tackle glioma remains to be challenging. Here, we present an advanced blood-brain barrier (BBB)-crossing nanovaccine based on cancer cell membrane-camouflaged poly(N-vinylcaprolactam) (PVCL) nanogels (NGs) incorporated with MnO2 and doxorubicin (DOX). We show that the disulfide bond-cross-linked redox-responsive PVCL NGs can be functionalized with dermorphin and imiquimod R837 through cell membrane functionalization. The formed functionalized PVCL NGs having a size of 220 nm are stable, can deplete glutathione, and responsively release both Mn2+ and DOX under the simulated tumor microenvironment to exert the chemo/chemodynamic therapy mediated by DOX and Mn2+, respectively. The combined therapy induces tumor immunogenic cell death to maturate dendritic cells (DCs) and activate tumor-killing T cells. Further, the nanovaccine composed of cancer cell membranes as tumor antigens, R837 as an adjuvant with abilities of DC maturation and macrophages M1 repolarization, and MnO2 with Mn2+-mediated stimulator of interferon gene activation of tumor cells can effectively act on both targets of tumor cells and immune cells. With the dermorphin-mediated BBB crossing, cell membrane-mediated homologous tumor targeting, and Mn2+-facilitated magnetic resonance (MR) imaging property, the designed NG-based theranostic nanovaccine enables MR imaging and combination chemo-, chemodynamic-, and imnune therapy of orthotopic glioma with a significantly decreased recurrence rate.

Macrophage membrane-camouflaged nanoclusters of ultrasmall iron oxide nanoparticles for precision glioma theranostics.

Developing effective nanomedicines to cross the blood-brain barrier (BBB) for efficient glioma theranostics is still considered to be a challenging task. Here, we describe the development of macrophage membrane (MM)-coated nanoclusters (NCs) of ultrasmall iron oxide nanoparticles (USIO NPs) with dual pH- and reactive oxygen species (ROS)-responsivenesses for magnetic resonance (MR) imaging and chemotherapy/chemodynamic therapy (CDT) of orthotopic glioma. Surface citrate-stabilized USIO NPs were solvothermally synthesized, sequentially modified with ethylenediamine and phenylboronic acid, and cross-linked with gossypol to form gossypol-USIO NCs (G-USIO NCs), which were further coated with MMs. The prepared MM-coated G-USIO NCs (G-USIO@MM NCs) with a mean size of 99.9 nm display tumor microenvironment (TME)-responsive gossypol and Fe release to promote intracellular ROS production and glutathione consumption. With the MM-mediated BBB crossing and glioma targeting, the G-USIO@MM NCs can specifically inhibit orthotopic glioma in vivo through the gossypol-mediated chemotherapy and Fe-mediated CDT. Meanwhile, USIO NPs can be dissociated from the NCs under the TME, thus allowing for effective T1-weighted glioma MR imaging. The developed G-USIO@MM NCs with simple components and drug as a crosslinker are promising for glioma theranostics, and may be extended to tackle other cancer types.

Dual-enzyme decorated semiconducting polymer nanoagents for second near-infrared photoactivatable ferroptosis-immunotherapy.

Enzymes provide a class of potential options to treat cancer, while the precise regulation of enzyme activities for effective and safe therapeutic actions has been poorly reported. Dual-enzyme decorated semiconducting polymer nanoagents for second near-infrared (NIR-II) photoactivatable ferroptosis-immunotherapy are reported in this study. Such nanoagents (termed SPHGA) consist of hemoglobin (Hb)-based semiconducting polymer (SP@Hb), adenosine deaminase (ADA) and glucose oxidase (GOx) with loadings in a thermal-responsive nanoparticle shell. NIR-II photoactivation of SPHGA results in the generation of heat to trigger on-demand releases of two enzymes (ADA and GOx) via destroying the thermal-responsive nanoparticle shells. In the tumor microenvironment, GOx oxidizes glucose to form hydrogen peroxide (H2O2), which promotes the Fenton reaction of iron in SP@Hb, resulting in an enhanced ferroptosis effect and immunogenic cell death (ICD). In addition, ADA degrades high-level adenosine to reverse the immunosuppressive microenvironment, thus amplifying antitumor immune responses. Via NIR-II photoactivatable ferroptosis-immunotherapy, SPHGA shows an improved effect to absolutely remove bilateral tumors and effectively suppress tumor metastases in subcutaneous 4T1 breast cancer models. This study presents a dual-enzyme-based nanoagent with controllable therapeutic actions for effective and precise cancer therapy.

Recent advances in zwitterionic nanoscale drug delivery systems to overcome biological barriers.

Nanoscale drug delivery systems (nDDS) have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects. Although several nDDS have been successfully approved for clinical use up to now, biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment. Polyethylene glycol (PEG)-modification (or PEGylation) has been regarded as the gold standard for stabilising nDDS in complex biological environment. However, the accelerated blood clearance (ABC) of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications. Zwitterionic polymer, a novel family of anti-fouling materials, have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility. Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues. More impressively, zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution, pressure gradients, impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications. The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS, which could facilitate their better clinical translation. Herein, we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlying mechanisms. Finally, prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.

High Intensity Focused Ultrasound-Driven Nanomotor for Effective Ferroptosis-Immunotherapy of TNBC.

The heterogeneity of triple-negative breast cancers (TNBC) remains challenging for various treatments. Ferroptosis, a recently identified form of cell death resulting from the unrestrained peroxidation of phospholipids, represents a potential vulnerability in TNBC. In this study, a high intensity focused ultrasound (HIFU)-driven nanomotor is developed for effective therapy of TNBC through induction of ferroptosis. Through bioinformatics analysis of typical ferroptosis-associated genes in the FUSCCTNBC dataset, gambogic acid is identified as a promising ferroptosis drug and loaded it into the nanomotor. It is found that the rapid motion of nanomotors propelled by HIFU significantly enhanced tumor accumulation and penetration. More importantly, HIFU not only actuated nanomotors to trigger effective ferroptosis of TNBC cells, but also drove nanomotors to activate ferroptosis-mediated antitumor immunity in primary and metastatic TNBC models, resulting in effective tumor regression and prevention of metastases. Overall, HIFU-driven nanomotors show great potential for ferroptosis-immunotherapy of TNBC.

Hypoxia-activated cascade nanovaccine for synergistic chemoembolization-immune therapy of hepatocellular carcinoma.

In this work, a promising treatment strategy for triggering robust antitumor immune responses in transarterial chemoembolization of hepatocellular carcinoma (HCC) is presented. The zeolitic imidazolate framework nanoparticles loaded with hypoxia-activated prodrug tirapazamine and immune adjuvant resiquimod facilitated in situ generation of nanovaccine via a facile approach. The nanovaccine can strengthen the ability of killing the liver cancer cells under hypoxic environment, while was capable of improving immunogenic tumor microenvironment and triggering strong antitumor immune responses by increasing the primary and distant intratumoral infiltration of immune cells such as cytotoxic T cells. Moreover, a porous microcarrier, approved by FDA as pharmaceutical excipient, was designed to achieve safe and effective delivery of the nanovaccine via transarterial therapy in rabbit orthotopic VX2 liver cancer model. The microcarrier exhibited the characteristics of excellent drug loading and occlusion of peripheral artery. The collaborative delivery of the microcarrier and nanovaccine demonstrated an exciting inhibitory effect on solid tumors and tumor metastases, which provided a great potential as novel combination therapy for HCC interventional therapy.

OX40L-expressing M1-like macrophage exosomes for cancer immunotherapy.

With only limited clinical patient benefit, focusing on new immune checkpoint pathways could be an important complement to current immune checkpoint drugs. In addition, not only does T cell-mediated adaptive immunity play an important role, but also macrophage-mediated innate immunity, due to its abundant presence in solid tumors. Here, we developed an engineered M1-like macrophage exosome, OX40L M1-exos. OX40L M1-exos can activate the adaptive immunity by activating the OX40/OX40L pathway and can reprogram M2-like tumor-associated macrophages into M1-like macrophages, thereby restoring and enhancing macrophage-mediated innate immunity. Our OX40L M1-exos achieved an effective synergistic effect of innate and adaptive immunity and achieved a potent therapeutic effect in a mouse breast cancer model, effectively inhibiting tumor growth and metastasis. These results suggest that OX40L M1-exos are an attractive therapeutic strategy and may be an important complement to current cancer immunotherapies.

Rapid sterilisation and diabetic cutaneous regeneration using cascade bio-heterojunctions through glucose oxidase-primed therapy.

The cutaneous wound in diabetic patients frequently encounters intractable pathogenic infections due to the hyperglycemia micromilieu which is conducive to bacterial growth and multiplication. Despite the extensive clinical use of antibiotics to treat bacterial infections, the emergence of drug-resistant and super pathogens as well as the potential side effects of antibiotics have elicited alarming challenges to public health. To address this daunting concern, we devise and develop a photo-activated cascade bio-heterojunctions (C-bio-HJs) for rapid sterilization and diabetic cutaneous regeneration. In the designed C-bio-HJs, photo-generated electron-hole pairs of graphite-phase carbon nitride (g-C3N4) are effectively separated with the marriage of molybdenum disulfide (MoS2), which achieves the augmented photodynamic antibacterial effect. Moreover, glucose oxidase (GOx) tethered on the bio-HJs catalyzes glucose into hydrogen peroxide (H2O2) in diabetic wounds for starvation therapy. Furthermore, Mo4+ enables the catalysis of H2O2 into a highly effective hydroxyl radical (·OH) for chemodynamic-photothermal combined antibacterial therapy. Both in vitro and in vivo results authenticate the cascading antibacterial properties and skin regeneration-promoting effects of the C-bio-HJs, which provide a facile strategy to combat diabetic wound healing through the synergistic GOx-primed dynamic therapies.

Injectable nano-composite hydrogels based on hyaluronic acid-chitosan derivatives for simultaneous photothermal-chemo therapy of cancer with anti-inflammatory capacity.

Nowadays, the photothermal therapy (PTT) has received widespread attention and research by rapidly killing tumors with local high temperature. However, due to the irregular edges of tumor and the blurred boundary between normal and necrotic tissues, the desirable treatment cannot be achieved by the single PTT, and excessive heat will cause serious inflammation in local tissues. Herein, an injectable composite hydrogel is prepared by the oxidized hyaluronic acid (OHA) and hydroxypropyl chitosan (HPCS) via the imine bonds, which is employed as the delivery substrate for functional substances. In the gel medium, the mesoporous polydopamine (MPDA) nanoparticles are incorporated as the high efficiency photothermal agent and a reservoir of DOX, which can achieve the good photothermal conversion performance and pulsed drug release. Besides, the addition of the curcumin-cyclodextrin host-guest inclusion complex (CUR@NH2-CD) in the composite hydrogel could reduce the inflammation caused by PTT. The composite hydrogel shows favorable the Hepa1-6 tumor inhibition in vivo by virtue of the comprehensive effect of the admired photothermal efficacy of MPDA, chemotherapy of DOX and anti-inflammatory of CUR. It can be predicted that the composite hydrogel has a broad prospect in the field of comprehensive therapy for tumor.

Application of stimuli-responsive nanomedicines for the treatment of ischemic stroke.

Ischemic stroke (IS) refers to local brain tissue necrosis which is caused by impaired blood supply to the carotid artery or vertebrobasilar artery system. As the second leading cause of death in the world, IS has a high incidence and brings a heavy economic burden to all countries and regions because of its high disability rate. In order to effectively treat IS, a large number of drugs have been designed and developed. However, most drugs with good therapeutic effects confirmed in preclinical experiments have not been successfully applied to clinical treatment due to the low accumulation efficiency of drugs in IS areas after systematic administration. As an emerging strategy for the treatment of IS, stimuli-responsive nanomedicines have made great progress by precisely delivering drugs to the local site of IS. By response to the specific signals, stimuli-responsive nanomedicines change their particle size, shape, surface charge or structural integrity, which enables the enhanced drug delivery and controlled drug release within the IS tissue. This breakthrough approach not only enhances therapeutic efficiency but also mitigates the side effects commonly associated with thrombolytic and neuroprotective drugs. This review aims to comprehensively summarize the recent progress of stimuli-responsive nanomedicines for the treatment of IS. Furthermore, prospect is provided to look forward for the better development of this field.

Self-Splittable Transcytosis Nanoraspberry for NIR-II Photo-Immunometabolic Cancer Therapy in Deep Tumor Tissue.

Cancer photo-immunotherapy (CPIT) as an ideal strategy can rapidly release hostile signals by appropriate dosage of focal laser irradiation to unmask primary tumor immunogenicity and can activate adaptive immunity to control distant metastases. However, many factors, including disordered immunometabolism, poor penetration of photothermal agents and immuno-regulators, inadequate laser penetration into the deep tumor region, restrict the therapeutic outcomes of CPIT. Here, a second near-infrared window (NIR-II) photo-immunometabolic cancer therapy (PICT) by a programmed raspberry-structured nanoadjuvant (PRNMT ) is presented that can potentiates efficient immunogenic cell death (ICD) in deep tumor tissue and alleviates immunometabolic disorder. The PRNMT is architected through self-assembly of indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor modified small-sized CuS nanoparticles (CuS5 ) and tumor microenvironment (TME) responsive cationized polymeric matrix. The TME can trigger the splitting and surface cationization of PRNMT into small cationized CuS5 that feature high transcytosis potential and TME immunometabolic regulation. Upon NIR-II irradiation, CuS5 induce homogeneous ICD and release immunometabolic regulator in deep tumor tissues, which ameliorates IDO-1 mediated immunometabolic disorder and further suppresses regulatory T cells infiltration. PRNMT mediated PICT effectively delays the primary murine mammary carcinoma 4T1 tumor growth and inhibits the lethal pulmonary metastasis in combination with programmed cell death protein 1 (PD1) blockade.

Recent advances in erythrocyte membrane-camouflaged nanoparticles for the delivery of anti-cancer therapeutics.

INTRODUCTION: Red blood cell (or erythrocyte) membrane-camouflaged nanoparticles (RBC-NPs) not only have a superior circulation life and do not induce accelerated blood clearance but also possess special functions, which offers great potential in cancer therapy. AREAS COVERED: This review focuses on the recent advances of RBC-NPs for delivering various agents to treat cancers in light of their vital role in improving drug delivery. Meanwhile, the construction and in vivo behavior of RBC-NPs are discussed to provide an in-depth understanding of the basis of RBC-NPs for improved cancer drug delivery. EXPERT OPINION: Although RBC-NPs are quite prospective in delivering anti-cancer therapeutics, they are still in their infancy stage and many challenges need to be overcome for successful translation into the clinic. The preparation and modification of RBC membranes, the optimization of coating methods, the scale-up production and the quality control of RBC-NPs, and the drug loading and release should be carefully considered in the clinical translation of RBC-NPs for cancer therapy.

Comparison of External Beam Radiation Therapy Modalities for Hepatocellular Carcinoma With Macrovascular Invasion: A Meta-Analysis and Systematic Review.

PURPOSE: We performed a systematic review and meta-analysis to compare external beam radiation therapy modalities for hepatocellular carcinoma (HCC) with macrovascular invasion (MVI). METHODS: Studies were selected from online databases from the date of inception to November 2021. The outcomes of interest were overall survival (OS), objective response rate (ORR), and local control rate (LCR). RESULTS: Forty-four studies (n = 3730) were selected from 1050 articles. The pooled 1-year OS were 60.9%, 45.3%, and 44.9 for particle radiotherapy (PRT) group, conventional radiotherapy (CRT), and stereotactic body radiotherapy (SBRT) group, respectively; p = 0.005 and 0.002 for PRT vs. CRT and SBRT, respectively. Both the PRT group and the SBRT group have the advantage over the CRT group in the pooled ORR. The PRT group showed significantly higher than the CRT group (p = 0.007) in LCR. For combination therapy, CRT plus transarterial chemoembolization can prolong survival than CRT alone (p = 0.006 for 1-year OS; p = 0.014 for 2-year OS). Among grade ≥ 3 complications, the most frequent type of toxicity in CRT, SBRT, PRT group was hematological toxicity, hepatotoxicity, dermatological toxicity, respectively. CONCLUSIONS: Among patients with HCC with MVI, the 1-year OS and the 2-year OS were both higher in the PRT group than in the CRT, SBRT groups. The ORR was similar between the PRT and SBRT groups. The combination therapy based on radiotherapy is expectable. PRT is associated with less complications than photon radiotherapy.

Extracellular matrix-degrading STING nanoagonists for mild NIR-II photothermal-augmented chemodynamic-immunotherapy.

Regulation of stimulator of interferon genes (STING) pathway using agonists can boost antitumor immunity for cancer treatment, while the rapid plasma clearance, limited membrane permeability, and inefficient cytosolic transport of STING agonists greatly compromise their therapeutic efficacy. In this study, we describe an extracellular matrix (ECM)-degrading nanoagonist (dNAc) with second near-infrared (NIR-II) light controlled activation of intracellular STING pathway for mild photothermal-augmented chemodynamic-immunotherapy of breast cancer. The dNAc consists of a thermal-responsive liposome inside loading with ferrous sulfide (FeS2) nanoparticles as both NIR-II photothermal converters and Fenton catalysts, 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) as the STING agonist, and an ECM-degrading enzyme (bromelain) on the liposome surface. Mild heat generated by dNAc upon NIR-II photoirradiation improves Fenton reaction efficacy to kill tumor cells and cause immunogenic cell death (ICD). Meanwhile, the generated heat triggers a controlled release of cGAMP from thermal-responsive liposomes to active STING pathway. The mild photothermal activation of STING pathway combined with ICD promotes anti-tumor immune responses, which leads to improved infiltration of effector T cells into tumor tissues after bromelain-mediated ECM degradation. As a result, after treatment with dNAc upon NIR-II photoactivation, both primary and distant tumors in a murine mouse model are inhibited and the liver and lung metastasis are effectively suppressed. This work presents a photoactivatable system for STING pathway and combinational immunotherapy with improved therapeutic outcome.

Tumor-Microenvironment-Responsive Nanomedicine for Enhanced Cancer Immunotherapy.

The past decades have witnessed great progress in cancer immunotherapy, which has profoundly revolutionized oncology, whereas low patient response rates and potential immune-related adverse events remain major clinical challenges. With the advantages of controlled delivery and modular flexibility, cancer nanomedicine has offered opportunities to strengthen antitumor immune responses and to sensitize tumor to immunotherapy. Furthermore, tumor-microenvironment (TME)-responsive nanomedicine has been demonstrated to achieve specific and localized amplification of the immune response in tumor tissue in a safe and effective manner, increasing patient response rates to immunotherapy and reducing the immune-related side effects simultaneously. Here, the recent progress of TME-responsive nanomedicine for cancer immunotherapy is summarized, which responds to the signals in the TME, such as weak acidity, reductive environment, high-level reactive oxygen species, hypoxia, overexpressed enzymes, and high-level adenosine triphosphate. Moreover, the potential to combine nanomedicine-based therapy and immunotherapeutic strategies to overcome each step of the cancer-immunity cycle and to enhance antitumor effects is discussed. Finally, existing challenges and further perspectives in this rising field with the hope for improved development of clinical applications are discussed.

Near-infrared light-triggered nano-prodrug for cancer gas therapy.

Gas therapy (GT) has attracted increasing attention in recent years as a new cancer treatment method with favorable therapeutic efficacy and reduced side effects. Several gas molecules, such as nitric oxide (NO), carbon monoxide (CO), hydrogen (H2), hydrogen sulfide (H2S) and sulfur dioxide (SO2), have been employed to treat cancers by directly killing tumor cells, enhancing drug accumulation in tumors or sensitizing tumor cells to chemotherapy, photodynamic therapy or radiotherapy. Despite the great progress of gas therapy, most gas molecules are prone to nonspecific distribution when administered systemically, resulting in strong toxicity to normal tissues. Therefore, how to deliver and release gas molecules to targeted tissues on demand is the main issue to be considered before clinical applications of gas therapy. As a specific and noninvasive stimulus with deep penetration, near-infrared (NIR) light has been widely used to trigger the cleavage and release of gas from nano-prodrugs via photothermal or photodynamic effects, achieving the on-demand release of gas molecules with high controllability. In this review, we will summarize the recent progress in cancer gas therapy triggered by NIR light. Furthermore, the prospects and challenges in this field are presented, with the hope for ongoing development.

Stimuli Responsive Nitric Oxide-Based Nanomedicine for Synergistic Therapy.

Gas therapy has received widespread attention from the medical community as an emerging and promising therapeutic approach to cancer treatment. Among all gas molecules, nitric oxide (NO) was the first one to be applied in the biomedical field for its intriguing properties and unique anti-tumor mechanisms which have become a research hotspot in recent years. Despite the great progress of NO in cancer therapy, the non-specific distribution of NO in vivo and its side effects on normal tissue at high concentrations have impaired its clinical application. Therefore, it is important to develop facile NO-based nanomedicines to achieve the on-demand release of NO in tumor tissue while avoiding the leakage of NO in normal tissue, which could enhance therapeutic efficacy and reduce side effects at the same time. In recent years, numerous studies have reported the design and development of NO-based nanomedicines which were triggered by exogenous stimulus (light, ultrasound, X-ray) or tumor endogenous signals (glutathione, weak acid, glucose). In this review, we summarized the design principles and release behaviors of NO-based nanomedicines upon various stimuli and their applications in synergistic cancer therapy. We also discuss the anti-tumor mechanisms of NO-based nanomedicines in vivo for enhanced cancer therapy. Moreover, we discuss the existing challenges and further perspectives in this field in the aim of furthering its development.

Recent progress in metal-organic framework/graphene-derived materials for energy storage and conversion: design, preparation, and application.

Graphene or chemically modified graphene, because of its high specific surface area and abundant functional groups, provides an ideal template for the controllable growth of metal-organic framework (MOF) particles. The nanocomposite assembled from graphene and MOFs can effectively overcome the limitations of low stability and poor conductivity of MOFs, greatly widening their application in the field of electrochemistry. Furthermore, it can also be utilized as a versatile precursor due to the tunable structure and composition for various derivatives with sophisticated structures, showing their unique advantages and great potential in many applications, especially energy storage and conversion. Therefore, the related studies have been becoming a hot research topic and have achieved great progress. This review summarizes comprehensively the latest methods of synthesizing MOFs/graphene and their derivatives, and their application in energy storage and conversion with a detailed analysis of the structure-property relationship. Additionally, the current challenges and opportunities in this field will be discussed with an outlook also provided.