Macrophages play an important role in cancer development and metastasis. Proinflammatory M1 macrophages can phagocytose tumor cells, while anti‐inflammatory M2 macrophages such as tumor‐associated ...macrophages (TAMs) promote tumor growth and invasion. Modulating the tumor immune microenvironment through engineering macrophages is efficacious in tumor therapy. M1 macrophages target cancerous cells and, therefore, can be used as drug carriers for tumor therapy. Herein, the strategies to engineer macrophages for cancer immunotherapy, such as inhibition of macrophage recruitment, depletion of TAMs, reprograming of TAMs, and blocking of the CD47‐SIRPα pathway, are discussed. Further, the recent advances in drug delivery using M1 macrophages, macrophage‐derived exosomes, and macrophage‐membrane‐coated nanoparticles are elaborated. Overall, there is still significant room for development in macrophage‐mediated immune modulation and macrophage‐mediated drug delivery, which will further enhance current tumor therapies against various malignant solid tumors, including drug‐resistant tumors and metastatic tumors.
Macrophages play important roles in tumor growth and treatment. Strategies to engineer tumor‐associated macrophages (TAMs) to combat tumors are summarized as follows: inhibiting macrophage recruitment, depleting TAMs, reprograming TAMs, and blocking the CD47‐SIRPα pathway. Furthermore, tumor‐targeting M1 macrophages are used in anti‐cancer drug delivery in three ways: as macrophages, macrophage‐derived exosomes, and macrophage‐coated nanoparticles acting as drug carriers.
Infectious diseases are a leading cause of mortality worldwide, with viruses and bacteria in particular having enormous impacts on global healthcare. One major challenge in combatting such diseases ...is a lack of effective drugs or specific treatments. In addition, drug resistance to currently available therapeutics and adverse effects caused by long-term overuse are both serious public health issues. A promising treatment strategy is to employ cell-membrane mimics as decoys to trap and to detain the pathogens. In this Perspective, we briefly review the infection mechanisms adopted by different pathogens at the cellular membrane interface and highlight the applications of cell-membrane-mimicking nanodecoys for systemic protection against infectious diseases. We also discuss the implication of nanodecoy–pathogen complexes in the development of vaccines. We anticipate this Perspective will provide new insights on design and development of advanced materials against emerging infectious diseases.
Among the many challenges in medicine, the treatment and cure of cancer remains an outstanding goal given the complexity and diversity of the disease. Nanotheranostics, the integration of therapy and ...diagnosis in nanoformulations, is the next generation of personalized medicine to meet the challenges in precise cancer diagnosis, rational management and effective therapy, aiming to significantly increase the survival rate and improve the life quality of cancer patients. Different from most conventional platforms with unsatisfactory theranostic capabilities, supramolecular cancer nanotheranostics have unparalleled advantages in early-stage diagnosis and personal therapy, showing promising potential in clinical translations and applications. In this review, we summarize the progress of supramolecular cancer nanotheranostics and provide guidance for designing new targeted supramolecular theranostic agents. Based on extensive state-of-the-art research, our review will provide the existing and new researchers a foundation from which to advance supramolecular cancer nanotheranostics and promote translationally clinical applications.
Supramolecular cancer nanotheranostics have shown promising potentials in early-stage diagnosis and personal therapy. Herein, we summarize the progress of supramolecular cancer nanotheranostics and provide guidance for designing new targeted supramolecular theranostic agents.
Bioorthogonal chemistry is a powerful tool to site-specifically activate drugs in living systems. Bioorthogonal reactions between a pair of biologically reactive groups can rapidly and specifically ...take place in a mild physiological milieu without perturbing inherent biochemical processes. Attributed to their high selectivity and efficiency, bioorthogonal reactions can significantly decrease background signals in bioimaging. Compared with metal-catalyzed bioorthogonal click reactions, metal-free click reactions are more biocompatible without the metal catalyst-induced cytotoxicity. Although a great number of bioorthogonal chemistry-based strategies have been reported for cancer theranostics, a comprehensive review is scarce to highlight the advantages of these strategies. In this review, recent progress in cancer theranostics guided by metal-free bioorthogonal click chemistry will be depicted in detail. The elaborate design as well as the advantages of bioorthogonal chemistry in tumor theranostics are summarized and future prospects in this emerging field are emphasized.
Immunotherapy has made remarkable strides in cancer therapy over the past decade. However, such emerging therapy still suffers from the low response rates and immune‐related adverse events. Various ...strategies have been developed to overcome these serious challenges. Therein, sonodynamic therapy (SDT), as a non‐invasive treatment, has received ever‐increasing attention especially in the treatment of deep‐seated tumors. Significantly, SDT can effectively induce immunogenic cell death to trigger systemic anti‐tumor immune response, termed sonodynamic immunotherapy. The rapid development of nanotechnology has revolutionized SDT effects with robust immune response induction. As a result, more and more innovative nanosonosensitizers and synergistic treatment modalities are established with superior efficacy and safe profile. In this review, the recent advances in cancer sonodynamic immunotherapy are summarized with a particular emphasis on how nanotechnology can be explored to harness SDT for amplifying anti‐tumor immune response. Moreover, the current challenges in this field and the prospects for its clinical translation are also presented. It is anticipated that this review can provide rational guidance and facilitate the development of nanomaterials‐assisted sonodynamic immunotherapy, helping to pave the way for next‐generation cancer therapy and eventually achieve a durable response in patients.
Sonodynamic immunotherapy has emerged as a rising star on the horizon of cancer immunotherapy in recent years. Specially, the advances of nanotechnology hold great promise to enhance such treatment efficacy and reduce toxicity simultaneously. An overview of nanomaterials‐assisted cancer sonodynamic immunotherapy is presented with a view to achieve its clinical patient benefits in the near future.
The clinical application of chemodynamic therapy is impeded by the insufficient intracellular H2O2 level in tumor tissues. Herein, we developed a supramolecular nanoparticle via a simple one‐step ...supramolecular polymerization‐induced self‐assembly process using platinum (IV) complex‐modified β‐cyclodextrin‐ferrocene conjugates as supramolecular monomers. The supramolecular nanoparticles could dissociate rapidly upon exposure to endogenous H2O2 in the tumor and release hydroxyl radicals as well as platinum (IV) prodrugs in situ, which is reduced into cisplatin to significantly promote the generation of H2O2 in the tumor tissue. Thus, the supramolecular nanomedicine overcomes the limitation of conventional chemodynamic therapy via the self‐augmented cascade radical generation and drug release. In addition, dissociated supramolecular nanoparticles could be readily excreted from the body via renal clearance to effectively avoid systemic toxicity and ensure long term biocompatibility of the nanomedicine. This work may provide new insights on the design and development of novel supramolecular nanoassemblies for cascade chemo/chemodynamic therapy.
We reported a one‐pot supramolecular polymerization‐induced self‐assembly approach to fabricate H2O2‐responsive nanomedicine with highly controllable drug loading and rapid clearance for self‐augmented synergistic chemo/chemodynamic cancer therapy.
Effectively activating macrophages against cancer is promising but challenging. In particular, cancer cells express CD47, a 'don't eat me' signal that interacts with signal regulatory protein alpha ...(SIRPα) on macrophages to prevent phagocytosis. Also, cancer cells secrete stimulating factors, which polarize tumor-associated macrophages from an antitumor M1 phenotype to a tumorigenic M2 phenotype. Here, we report that hybrid cell membrane nanovesicles (known as hNVs) displaying SIRPα variants with significantly increased affinity to CD47 and containing M2-to-M1 repolarization signals can disable both mechanisms. The hNVs block CD47-SIRPα signaling axis while promoting M2-to-M1 repolarization within tumor microenvironment, significantly preventing both local recurrence and distant metastasis in malignant melanoma models. Furthermore, by loading a stimulator of interferon genes (STING) agonist, hNVs lead to potent tumor inhibition in a poorly immunogenic triple negative breast cancer model. hNVs are safe, stable, drug loadable, and suitable for genetic editing. These properties, combined with the capabilities inherited from source cells, make hNVs an attractive immunotherapy.
Zika virus (ZIKV) infection is a public health emergency and host innate immunity is essential for the control of virus infection. The NLRP3 inflammasome plays a key role in host innate immune ...responses by activating caspase-1 to facilitate interleukin-1β (IL-1β) secretion. Here we report that ZIKV stimulates IL-1β secretion in infected patients, human PBMCs and macrophages, mice, and mice BMDCs. The knockdown of NLRP3 in cells and knockout of NLRP3 in mice inhibit ZIKV-mediated IL-1β secretion, indicating an essential role for NLRP3 in ZIKV-induced IL-1β activation. Moreover, ZIKV NS5 protein is required for NLRP3 activation and IL-1β secretion by binding with NLRP3 to facilitate the inflammasome complex assembly. Finally, ZIKV infection in mice activates IL-1β secretion, leading to inflammatory responses in the mice brain, spleen, liver, and kidney. Thus we reveal a mechanism by which ZIKV induces inflammatory responses by facilitating NLRP3 inflammasome complex assembly and IL-1β activation.
Extracellular vesicles (EVs) are nano-sized, natural, cell-derived vesicles that contain the same nucleic acids, proteins, and lipids as their source cells. Thus, they can serve as natural carriers ...for therapeutic agents and drugs, and have many advantages over conventional nanocarriers, including their low immunogenicity, good biocompatibility, natural blood-brain barrier penetration, and capacity for gene delivery. This review first introduces the classification of EVs and then discusses several currently popular methods for isolating and purifying EVs, EVs-mediated drug delivery, and the functionalization of EVs as carriers. Thereby, it provides new avenues for the development of EVs-based therapeutic strategies in different fields of medicine. Finally, it highlights some challenges and future perspectives with regard to the clinical application of EVs.
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the urgent need to rapidly develop therapeutic strategies for such emerging viruses ...without effective vaccines or drugs. Here, we report a decoy nanoparticle against COVID-19 through a powerful two-step neutralization approach: virus neutralization in the first step followed by cytokine neutralization in the second step. The nanodecoy, made by fusing cellular membrane nanovesicles derived from human monocytes and genetically engineered cells stably expressing angiotensin converting enzyme II (ACE2) receptors, possesses an antigenic exterior the same as source cells. By competing with host cells for virus binding, these nanodecoys effectively protect host cells from the infection of pseudoviruses and authentic SARS-CoV-2. Moreover, relying on abundant cytokine receptors on the surface, the nanodecoys efficiently bind and neutralize inflammatory cytokines including interleukin 6 (IL-6) and granulocyte–macrophage colony-stimulating factor (GM-CSF), and significantly suppress immune disorder and lung injury in an acute pneumonia mouse model. Our work presents a simple, safe, and robust antiviral nanotechnology for ongoing COVID-19 and future potential epidemics.
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