Biomimetic nanoparticles drive the mechanism understanding of shear-wave elasticity stiffness in triple negative breast cancers to predict clinical treatment

In clinical practice,we noticed that triple negative breast cancer(TNBC)patients had higher shear-wave elasticity(SWE)stiffness than non-TNBC patients and a higherα-SMA expression was found in TNBC tissues than the non-TNBC tissues.Moreover,SWE stiffness also shows a clear correlation to neoadjuvant response efficiency.To elaborate this phenomenon,TNBC cell membrane-modified polylactide acid-glycolic acid(PLGA)nanoparticle was fabricated to specifically deliver artesunate to regulate SWE stiffness through inhibiting CAFs functional status.As tested in MDA-MB-231 and E0771 orthotopic tumor models,CAFs functional status inhibited by 231M-ARS@PLGA nanoparticles(231M-AP NPs)had reduced the SWE stiffness as well as attenuated hypoxia of tumor as tumor soil loosening agent which amplified the antitumor effects of paclitaxel and PD1 inhibitor.Single-cell sequencing indicated that the two main CAFs(extracellular matrix and wound healing CAFs)that produces extracellular matrix could influence the tumor SWE stiffness as well as the antitumor effect of drugs.Further,biomimetic nanoparticles inhibited CAFs function could attenuate tumor hypoxia by increasing proportion of inflammatory blood vessels and oxygen transport capacity.Therefore,our finding is fundamental for understanding the role of CAFs on affecting SWE stiffness and drugs antitumor effects,which can be further implied in the potential clinical theranostic predicting in neoadjuvant therapy efficacy through non-invasive analyzing of SWE imaging.

Biomimetic nanoparticles for inflammation targeting

There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels,and molecular mediators directed against harmful stimuli, is closely associated with many human diseases.As a result, biomimetic nanoparticles mimicking immune cells can help achieve molecular imaging and precise drug delivery to these inflammatory sites. This review is focused on inflammation-targeting biomimetic nanoparticles and will provide an in-depth look at the design of these nanoparticles to maximize their benefits for disease diagnosis and treatment.

ROS-responsive biomimetic nanoparticles for potential application in targeted anti-atherosclerosis

The development of nanomedicines provides new opportunities for the treatment of atherosclerosis(AS)due to their great advantages such as the improved drug solubility,enhanced bioavailability and reduced side effects.Despite these advantages,nanomedicines are still facing some challenges.The problems remain in the short circulation life,lack of specific targeting and poor drug release controllability.In order to overcome the shortages of conventional nanomedicines,the combination of biomimetic strategy with smart nanoagents has been proposed.In light with the high reactive oxygen species(ROS)level in AS microenvironment and the fact that macrophages play a critical role in the pathogenesis of AS,we fabricated ROS-responsive biomimetic nanoparticles(NPs),which camouflaged macrophage membrane(MM)on ROS-responsive NPs loaded with rapamycin(RNPs)for potential application in AS therapy.The resulting ROSresponsive biomimetic NPs(MM/RNPs)exhibited favorable hydrodynamic size with negative surface charge,retained the functional proteins from MM,and showed ROS-responsive drug release.Because of the biomimetic camouflaging on surface,MM/RNPs could effectively escape from macrophages uptake and target to inflammatory endothelial cells.Meanwhile,MM/RNPs could inhibit the proliferation of macrophages and smooth muscle cells in vitro.Furthermore,the MM-coated NPs were found to be nontoxic in both cytotoxicity assay and in vivo toxicity evaluation.Consequently,these results demonstrated that MM/RNPs could be a potential candidate of drug delivery system for safe and effective anti-AS applications.

Editorial for biomimetic nanoparticles for drug delivery

The origins of controlled release drug delivery could be dated back to the 1950s.The Spansule technology was developed to deliver a drug for 12 h in 1952.Compared with taking a drug every 6 h or every8 h,twice-a-day formulation was revolutionary in improving the patients’compliance and convenience1.Since then,advances in drug delivery technologies have introduced numerous formulations

Editor Profile: Guest Editor of Special Issue on Biomimetic Nanoparticles for Drug Delivery

Dr.Jianxin Wang is a professor of pharmaceutics at Fudan University,School of Pharmacy.He received his Ph.D.in pharmaceutics from West China University of Medical Sciences in 1999.He worked for Shanghai Institute of Chinese Materia Medica from July 1999 to April 2005.Dr.Wang became a faculty member of School of Pharmacy,Fudan University in 2005.He worked as a visiting scholar in the College of Pharmacy,

A homologous and molecular dual-targeted biomimetic nanocarrier for EGFR-related non-small cell lung cancer therapy

The abnormal activation of epidermal growth factor receptor(EGFR)drives the development of non-small cell lung cancer(NSCLC).The EGFR-targeting tyrosine kinase inhibitor osimertinib is frequently used to clinically treat NSCLC and exhibits marked efficacy in patients with NSCLC who have an EGFR mutation.However,free osimertinib administration exhibits an inadequate response in vivo,with only~3%patients demonstrating a complete clinical response.Consequently,we designed a biomimetic nanoparticle(CMNP^(@Osi))comprising a polymeric nanoparticle core and tumor cell-derived membrane-coated shell that combines membrane-mediated homologous and molecular targeting for targeted drug delivery,thereby supporting a dual-target strategy for enhancing osimertinib efficacy.After intravenous injection,CMNP^(@Osi)accumulates at tumor sites and displays enhanced uptake into cancer cells based on homologous targeting.Osimertinib is subsequently released into the cytoplasm,where it suppresses the phosphorylation of upstream EGFR and the downstream AKT signaling pathway and inhibits the proliferation of NSCLC cells.Thus,this dual-targeting strategy using a biomimetic nanocarrier can enhance molecular-targeted drug delivery and improve clinical efficacy.

Neutrophil membrane-camouflaged nanoparticles alleviate inflammation and promote angiogenesis in ischemic myocardial injury

Acute myocardial infarction(AMI)induces a sterile inflammatory response,leading to cardiomyocyte damage and adverse cardiac remodeling.Interleukin-5(IL-5)plays an essential role in developing eosinophils(EOS),which are beneficial for the resolution of inflammation.Furthermore,the proangiogenic properties of IL-5 also contribute to tissue healing following injury.Therefore,targeted delivery of IL-5 is an innovative therapeutic approach for treating AMI.It has been shown that conventional IL-5 delivery can result in undesirable adverse effects and potential drug overdose.In this study,we successfully synthesized a biomimetic IL-5 nanoparticle by camouflaging the IL-5 nanoparticle in a neutrophilic membrane.The administration of neutrophil membrane-camouflaged nanoparticles(NM-NPIL-5)in the in vivo model showed that these nanoparticles promoted EOS accumulation and angiogenesis in the infarcted myocardium,thereby limiting adverse cardiac remodeling after AMI.Our results also demonstrated that the NM-NPIL-5 could serve as neutrophil“decoys”to adsorb and neutralize the elevated neutrophil-related cytokines in the injured heart by inheriting multiple receptors from their“parent”neutrophils.Finally,the targeted delivery of NM-NPIL-5 protected the cardiomyocytes from excessive inflammatory-induced apoptosis and maintained cardiac function.Our findings provided a promising cardiac detoxification agent for acute cardiac injury.

Immune cell membrane-based biomimetic nanomedicine for treating cancer metastasis

Metastasis is the leading cause of cancer-related death.Despite extensive treatment,the prognosis for patients with metastatic cancer remains poor.In addition to conventional surgical resection,radiotherapy,immunotherapy,chemotherapy,and targeted therapy,various nanobiomaterials have attracted attention for their enhanced antitumor performance and low off-target effects.However,nanomedicines exhibit certain limitations in clinical applications,such as rapid clearance from the body,low biological stability,and poor targeting ability.Biomimetic methods utilize the natural biomembrane to mimic or hybridize nanoparticles and circumvent some of these limitations.Considering the involvement of immune cells in the tumor microenvironment of the metastatic cascade,biomimetic methods using immune cell membranes have been proposed with unique tumor-homing ability and high biocompatibility.In this review,we explore the impact of immune cells on various processes of tumor metastasis.Furthermore,we summarize the synthesis and applications of immune cell membrane-based nanocarriers increasing therapeutic efficacy against cancer metastases via immune evasion,prolonged circulation,enhanced tumor accumulation,and immunosuppression of the tumor microenvironment.Moreover,we describe the prospects and existing challenges in clinical translation.

Bio-Nanocarriers for Lung Cancer Management:Befriending the Barriers

ABSTRACT Lung cancer is a complex thoracic malignancy developing consequential to aberrations in a myriad of molecular and biomolecular signaling pathways.It is one of the most lethal forms of cancers accounting to almost 1.8 million new annual incidences,bearing overall mortality to incidence ratio of 0.87.The dismal prognostic scenario at advanced stages of the disease and metastatic/resistant tumor cell populations stresses the requisite of advanced translational interdisciplinary interventions such as bionanotechnology.This review article deliberates insights and apprehensions on the recent prologue of nanobioengineering and bionanotechnology as an approach for the clinical management of lung cancer.The role of nanobioengineered(bio-nano)tools like bio-nanocarriers and nanobiodevices in secondary prophylaxis,diagnosis,therapeutics,and theranostics for lung cancer management has been discussed.Bioengineered,bioinspired,and biomimetic bio-nanotools of considerate translational value have been reviewed.Perspectives on existent oncostrategies,their critical comparison with bio-nanocarriers,and issues hampering their clinical bench side to bed transformation have also been summarized.

Hippo pathway-manipulating neutrophil-mimic hybrid nanoparticles for cardiac ischemic injury via modulation of local immunity and cardiac regeneration

The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines.Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules.Here,we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR,fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles(MSNs)loaded with microRNA-10b.The hybrid membrane could endow nanoparticles with strong capacity to migrate into infammatory sites and neutralize proinfammatory cytokines and increase the delivery efficiency of microRNA-1Ob into adult mammalian cardiomyocytes(CMs)by fusing with cell membranes and leading to the release of MSNs-miR into cytosol.Upon NM@miR administration,this nanoparticle could home to the injured myocardium,restore the local immunity,and efficiently deliver microRNA-1Ob to cardiomyocytes,which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-1Ob.This combination therapy could finally improve cardiac function and mitigate ventricular remodeling.Consequently,this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.

Erythrocyte membrane encapsulated gambogic acid nanoparticles as a therapeutic for hepatocellular carcinoma

Gambogic acid(GA)is a potential clinical anticancer drug that can exert antitumor effects via various molecular mechanisms.Notwithstanding,GA’s low water solubility,poor stability,short half-life,and unavoidable toxic side effects have significantly hampered its clinical application.Erythrocyte membranecoated nanoparticles(RBCM-NPs)improve drug’s physicochemical properties,biocompatibility,and pharmacokinetic behaviors,allowing for long-term drug circulation and passive targeting.In this study,a novel biomimetic drug delivery system(DDS)against hepatocellular carcinoma was prepared by covering RBCM on GPP-NPs(GA-loaded m PEG-PLA NPs)to develop the RBC@GPP-NPs.In comparison to RBCM-free nanoparticles and free GA,RBC@GPP-NPs improved the drug’s water solubility,stability,safety,and antitumor activity in vivo.We expect that this bionic nanoparticle composite can expand the clinical applicability of GA and provide a feasible solution for the research and development of GA’s nano-formulation.

Cell membrane-based nanoparticles: a new biomimetic platform for tumor diagnosis and treatment

Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems(fast elimination in circulation) to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles(CMBNPs) are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field.

Neddylation suppression by a macrophage membrane-coated nanoparticle promotes dual immunomodulatory repair of diabetic wounds

Oxidative stress,infection,and vasculopathy caused by hyperglycemia are the main barriers for the rapid repair of foot ulcers in patients with diabetes mellitus(DM).In recent times,the discovery of neddylation,a new type of post-translational modification,has been found to regulate various crucial biological processes including cell metabolism and the cell cycle.Nevertheless,its capacity to control the healing of wounds in diabetic patients remains unknown.This study shows that MLN49224,a compound that inhibits neddylation at low concentrations,enhances the healing of diabetic wounds by inhibiting the polarization of M1 macrophages and reducing the secretion of inflammatory factors.Moreover,it concurrently stimulates the growth,movement,and formation of blood vessel endothelial cells,leading to expedited healing of wounds in individuals with diabetes.The drug is loaded into biomimetic macrophage-membrane-coated PLGA nanoparticles(M-NPs/MLN4924).The membrane of macrophages shields nanoparticles from being eliminated in the reticuloendothelial system and counteracts the proinflammatory cytokines to alleviate inflammation in the surrounding area.The extended discharge of MLN4924 from M-NPs/MLN4924 stimulates the growth of endothelial cells and the formation of tubes,along with the polarization of macrophages towards the anti-inflammatory M2 phenotype.By loading M-NPs/MLN4924 into a hydrogel,the final formulation is able to meaningfully repair a diabetic wound,suggesting that M-NPs/MLN4924 is a promising engineered nanoplatform for tissue engineering.

Advances of biological-camouflaged nanoparticles delivery system

Nanoparticles(NPs)which are innovation and research focus in drug delivery systems,still have some disadvantages limiting its application in clinical use,such as short circulation time,recognition and clearance by reticuloendothelial system(RES)and passive targeting in certain organs.However,the recent combination of natural components and nanotechnology has offered new solutions to address these problems.A novel biomimetic platform consisting of nanoparticle core and membrane shell,such as cell membrane,exosome or vesicle vastly improves properties of nanoparticles.These coated nanoparticles can replicate the unique functions of the membrane,such as prolonged blood circulation,active targeting capability and enhanced internalization.In this review,we focus on the newest development of biological-camouflaged nanoparticles and mainly introduce its application related to cancer therapy and toll-like receptor.

Cell membrane-coated nanoparticles for immunotherapy

Nanoparticle-based disease detection, prevention and therapies have gained increased interests in biomedical applications, owing to their significant advantages in therapeutic efficacy and safety. Nonetheless, suffering from the challenges including fast recognition and clearance of foreign nanoparticles by innate immune system before arriving at diseased regions, clinical applications of nanoparticles are usually intercepted. Among various strategies for reducing non-specific phagocytosis and enhancing diseasetargeting efficiency of nanoparticles, membrane coating nanotechnology exhibits great potential in the disease diagnosis and therapeutics due to both the structural and functional preservation of membrane proteins from source cells. Benefiting the inherited immune-regulation capacities, this review mainly summarized the latest development of such biomimetic nanoparticles for immunotherapy in treating immune-related diseases including microbial infections, inflammation, tumor and autoimmune diseases.

Cell membrane-coated nanoparticles for tumor-targeted drug delivery

Nanoparticles can be enriched at tumor site and improve the therapeutic efficacy of many chemother- apy drugs with the well-known enhanced permeability and retention （EPR） effect. While conventional preparations of materials for nanoscale drug delivery system mainly focused on chemical synthesis, recently the combination of synthetic carrier and natural biomimetic carrier has gained more and more attention. As a new generation of biomimetic nanoparticles, cell membrane-coated nanoparticles combine the complex biological functions of natural membranes and the physicochemical properties of synthetic nanomaterials for a more effective drug delivery. Herein, we briefly review the recent advances on cell membrane-coated nanoparticles for tumor-targeted drug delivery via the prolonging systemic circulation lifetime and the active targeting effect. Since the preferential accumulation of cell membrane-coated nanopar- ticles in tumor site, they are able to improve the therapeutic efficacy of conventional chemotherapy drugs in antitumor treatment as well as to reduce the systemic toxicity. We also introduce a systematic targeted strategy for the promising application of this platform on brain tumors.

Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulation

Retinal pigment epithelial(RPE) is primarily impaired in age-related macular degeneration(AMD), leading to progressive loss of photoreceptors and sometimes choroidal neovascularization(CNV). mTOR has been proposed as a promising therapeutic target, while the usage of its specific inhibitor,rapamycin, was greatly limited. To mediate the mTOR pathway in the retina by a noninvasive approach, we developed novel biomimetic nanocomplexes where rapamycin-loaded nanoparticles were coated with cell membrane derived from macrophages(termed as MRaNPs). Taking advantage of the macrophage-inherited property, intravenous injection of MRaNPs exhibited significantly enhanced accumulation in the CNV lesions, thereby increasing the local concentration of rapamycin. Consequently, MRaNPs effectively downregulated the mTOR pathway and attenuate angiogenesis in the eye. Particularly, MRaNPs also efficiently activated autophagy in the RPE, which was acknowledged to rescue RPE in response to deleterious stimuli. Overall, we design and prepare macrophage-disguised rapamycin nanocarriers and demonstrate the therapeutic advantages of employing biomimetic cell membrane materials for treatment of AMD.

Bioactive nanotherapeutic trends to combat triple negative breast cancer

The management of aggressive breast cancer,particularly,triple negative breast cancer(TNBC)remains a formidable challenge,despite treatment advancement.Although newer therapies such as atezolizumab,olaparib,and sacituzumab can tackle the breast cancer prognosis and/or progression,but achieved limited survival benefit(s).The current research efforts are aimed to develop and implement strategies for improved bioavailability,targetability,reduce systemic toxicity,and enhance therapeutic outcome of FDA-approved treatment regimen.This review presents various nanoparticle technology mediated delivery of chemotherapeutic agent(s)for breast cancer treatment.This article also documents novel strategies to employ cellular and cell membrane cloaked(biomimetic)nanoparticles for effective clinical translation.These technologies offer a safe and active targeting nanomedicine for effective management of breast cancer,especially TNBC.