Macrophage membrane-coated nanovesicles for dual-targeted drug delivery to inhibit tumor and induce macrophage polarization

Background:Immunosuppressive M2 macrophages in the tumor microenvironment(TME)can mediate the therapeutic resistance of tumors,and seriously affect the clinical efficacy and prognosis of tumor patients.This study aims to develop a novel drug delivery system for dual-targeting tumor and macrophages to inhibit tumor and induce macrophage polarization.Methods:The anti-tumor effects of methyltransferase like 14(METTL14)were investigated both in vitro and in vivo.The underlying mechanisms of METTL14 regulating macrophages were also explored in this study.We further constructed the cyclic(Arg-Gly-Asp)(cRGD)peptide modified macrophage membrane-coated nanovesicles to co-deliver METTL14 and the TLR4 agonist.Results:We found that METTL14 significantly inhibits the growth of tumor in vitro.METTL14 might downregulate TICAM2 and inhibit the Toll-like receptor 4(TLR4)pathway of macrophages,meanwhile,the combination of METTL14 and the TLR4 agonist could induce M1 polarization of macrophages.Macrophage membrane-coated nanovesicles are characterized by easy modification,drug loading,and dual-targeting tumor and macrophages,and cRGD modification can further enhance its targeting ability.It showed that the nanovesicles could improve the in vivo stability of METTL14,and dual-target tumor and macrophages to inhibit tumor and induce M1 polarization of macrophages.Conclusions:This study anticipates achieving the dual purposes of tumor inhibition and macrophage polarization,and providing a new therapeutic strategy for tumors.

Cell membrane coated-nanoparticles for cancer immunotherapy

Cancer immunotherapy can effectively inhibit cancer progression by activating the autoimmune system, with low toxicity and high effectiveness. Some of cancer immunotherapy had positive effects on clinical cancer treatment. However, cancer immunotherapy is still restricted by cancer heterogeneity, immune cell disability, tumor immunosuppressive microenvironment and systemic immune toxicity. Cell membrane-coated nanoparticles(CMCNs) inherit abundant source cell-relevant functions, including “self” markers, cross-talking with the immune system, biological targeting, and homing to specific regions. These enable them to possess preferred characteristics, including better biological compatibility, weak immunogenicity, immune escaping, a prolonged circulation, and tumor targeting.Therefore, they are applied to precisely deliver drugs and promote the effect of cancer immunotherapy.In the review, we summarize the latest researches of biomimetic CMCNs for cancer immunotherapy,outline the existing specific cancer immune therapies, explore the unique functions and molecular mechanisms of various cell membrane-coated nanoparticles, and analyze the challenges which CMCNs face in clinical translation.

Nature-inspired nanocarriers for improving drug therapy of atherosclerosis

Atherosclerosis(AS)has emerged as one of the prevalent arterial vascular diseases characterized by plaque and inflammation,primarily causing disability and mortality globally.Drug therapy remains the main treatment for AS.However,a series of obstacles hinder effective drug delivery.Nature,from natural micro-/nano-structural biological particles like natural cells and extracellular vesicles to the distinctions between the normal and pathological microenvironment,offers compelling solutions for efficient drug delivery.Nature-inspired nanocarriers of synthetic stimulus-responsive materials and natural components,such as lipids,proteins and membrane structures,have emerged as promising candidates for fulfilling drug delivery needs.These nanocarriers offer several advantages,including prolonged blood circulation,targeted plaque delivery,targeted specific cells delivery and controlled drug release at the action site.In this review,we discuss the nature-inspired nanocarriers which leverage the natural properties of cells or the microenvironment to improve atherosclerotic drug therapy.Finally,we provide an overview of the challenges and opportunities of applying these innovative nature-inspired nanocarriers.