Biomimetic Nanomedicine Research Articles

Biomimetic Nanoparticle with Glutathione Depletion and Amplified ROS Generation Capabilities for Synergistic Chemo-Sonodynamic Therapy in Squamous Cell Carcinomas.

Nanomedicines for combining chemotherapy and sonodynamic therapy (SDT) have enormous potential in squamous cell carcinoma treatment. However, the therapeutic efficacy of noninvasive SDT is severely limited because the generation of reactive oxygen species (ROS) by sonosensitizers is highly dependent on the levels of intracellular excess glutathione (GSH) in the tumor cells. To overcome this barrier, a red blood cell (RBC) membrane-camouflaged nanomedicine consisting of GSH-sensitive polyphosphoester (SS-PPE) and ROS-sensitive polyphosphoester (S-PPE) was designed for the simultaneous delivery of the sonosensitizer hematoporphyrin (HMME) and chemotherapeutic agent docetaxel (DTXL) for effectively enhanced antitumor efficacy. In vitro and in vivo studies demonstrated that HMME-driven ROS generation under ultrasound (US) inhibited SCC7 cell proliferation and accelerated DTXL release to further kill tumor cells via the hydrophobic-hydrophilic transition of the nanoparticle core. Meanwhile, the disulfide bond of SS-PPE effectively consumes GSH to prevent ROS consumption. This biomimetic nanomedicine provides GSH depletion and amplified ROS generation capabilities to achieve a novel synergistic chemo-SDT strategy for squamous cell carcinomas.

Long Circulating Cancer Cell-Targeted Bionic Nanocarriers Enable Synergistic Combinatorial Therapy in Colon Cancer

Cancer nanomedicine treatment aims to achieve highly specific targeting and localization to cancer cells. Coating of nanoparticles with cell membranes endows them with homologous cellular mimicry, enabling nanoparticles to acquire new functions and properties, including homologous targeting and long circulation in vivo, and can enhance internalization by homologous cancer cells. Herein, we fused a human-derived HCT116 colon cancer cell membrane (cM) with a red blood cell membrane (rM) to fabricate an erythrocyte-cancer cell hybrid membrane (hM). Oxaliplatin and chlorin e6 (Ce6) co-encapsulated reactive oxygen species-responsive nanoparticles (NPOC) were camouflaged by hM and obtained a hybrid biomimetic nanomedicine (denoted as hNPOC) for colon cancer therapy. hNPOC exhibited prolonged circulation time and recognized homologous targeting ability in vivo since both rM and HCT116 cM proteins were maintained on the hNPOC surface. hNPOC showed enhanced homologous cell uptake in vitro and considerable homologous self-localization in vivo, producing effective synergistic chemophotodynamic therapy efficacy under irradiation with a homologous HCT116 tumor compared to that with a heterologous tumor. Together, the biomimetic hNPOC nanoparticles showed prolonged blood circulation and preferential cancer cell-targeted function in vivo to provide a bioinspired strategy for chemophotodynamic synergistic therapy of colon cancer.

RGD peptide modified RBC membrane functionalized biomimetic nanoparticles for thrombolytic therapy

In recent years, the fabrication of nano-drug delivery systems for targeted treatment of thrombus has become a research hotspot. In this study, we intend to construct a biomimetic nanomedicine for targeted thrombus treatment. The poly lactic-co-glycolic acid (PLGA) was selected as the nanocarrier material. Then, urokinase and perfluoro-n-pentane (PFP) were co-loaded into PLGA by the double emulsification solvent evaporation method to prepare phase change nanoparticles PPUNPs. Subsequently, the RGD peptide-modified red blood cell membrane (RBCM) was coated on the surface of PPUNPs to prepare a biomimetic nano-drug carrier (RGD-RBCM@PPUNPs). The as-prepared RGD-RBCM@PPUNPs possessed a “core-shell” structure, have good dispersibility, and inherited the membrane protein composition of RBCs. Under ultrasound stimulation, the loaded urokinase could be rapidly released. In vitro cell experiments showed that RGD-RBCM@PPUNPs had good hemocompatibility and cytocompatibility. Due to the coated RGD-RBC membrane, RGD-RBCM@PPUNPs could effectively inhibit the uptake of macrophages. In addition, RGD-RBCM@PPUNPs showed better thrombolytic function in vitro. Overall, the results suggested that this biomimetic nanomedicine provided a promising therapeutic strategy for the targeted therapy of thrombosis.Graphical

Reshaping cardiac microenvironments by macrophage-derived extracellular vesicles-coated Pd@CeO2 heterostructures for myocardial ischemia/reperfusion injury therapy

Myocardial Ischemia/Reperfusion (MI/R) injury, a globally leading cause of mortality and disability, is commonly characterized by myriad inflammatory microenvironments, e.g. high level of reactive oxygen species (ROS), which has a high association with the consequent cell apoptosis and myocardial fibrosis. Herein, a reshaping strategy of cardiac microenvironments has been developed for relieving MI/R injury based on a biomimetic nanosystem (Pd@CeO2-M), which is composed of exterior macrophage-derived extracellular vesicles (MEVs) and encapsulated Pd@CeO2 heterostructures. Due to rapid electrons transfer on the interface, the Pd@CeO2 heterostructures exhibited outstanding ROS scavenging ability. The expression of Mac-1 and CD44 on the surface of Pd@CeO2-M contributes to adsorbing to the inflamed endothelium and efficient cellular uptake within damaged cardiac microenvironments, thus allowing for inflammation-targeting ability. In the mouse model of MI/R injury, Pd@CeO2-M accumulated and remained in the heart region over 24 hours. More importantly, Pd@CeO2-M regulated immune response and promoted anti-apoptotic and anti-inflammatory processes via upregulating the PI3K/Akt signaling pathway and inhibiting the TLR4/p38MAPK and TLR4/NF-κB signaling pathways, dissipated interstitial edema, triggered prominent angiogenesis, and ultimately improved cardiac function and ventricular remodeling. Overall, the Pd@CeO2-M heterostructures will provide an ideal paradigm of biomimetic nanomedicine confronting inflammatory diseases.

Versatile biomimetic nanomedicine for treating cancer and inflammation disease.

Nanosized drug delivery systems (NDDSs) have emerged as a powerful tool to optimize drug delivery in complex diseases, including cancer and inflammation. However, the therapeutic effect of NDDSs is still far from satisfactory due to their poor circulation time, low delivery efficiency, and innate toxicity. Fortunately, biomimetic approaches offer new opportunities to develop nanomedicine, which is derived from a variety of native biomolecules including cells, exosomes, bacteria, and so on. Since inheriting the superior biocompatibility and versatile functions of natural materials, biomimetic nanomedicine can mimic biological processes, prolong blood circulation, and lower immunogenicity, serving as a desired platform for precise drug delivery for treating cancer and inflammatory disease. In this review, we outline recent advances in biomimetic NDDSs, which consist of two concepts: biomimetic exterior camouflage and bioidentical molecule construction. We summarize engineering strategies that further functionalized current biomimetic NDDSs. A series of functional biomimetic NDDSs created by our group are introduced. We conclude with an outlook on remaining challenges and possible directions for biomimetic NDDSs. We hope that better technologies can be inspired and invented to advance drug delivery systems for cancer and inflammation therapy.

A Bird's Eye View of Various Cell-Based Biomimetic Nanomedicines for the Treatment of Arthritis.

Arthritis is the inflammation and tenderness of the joints because of some metabolic, infectious, or constitutional reasons. Existing arthritis treatments help in controlling the arthritic flares, but more advancement is required to cure arthritis meticulously. Biomimetic nanomedicine represents an exceptional biocompatible treatment to cure arthritis by minimizing the toxic effect and eliminating the boundaries of current therapeutics. Various intracellular and extracellular pathways can be targeted by mimicking the surface, shape, or movement of the biological system to form a bioinspired or biomimetic drug delivery system. Different cell-membrane-coated biomimetic systems, and extracellular-vesicle-based and platelets-based biomimetic systems represent an emerging and efficient class of therapeutics to treat arthritis. The cell membrane from various cells such as RBC, platelets, macrophage cells, and NK cells is isolated and utilized to mimic the biological environment. Extracellular vesicles isolated from arthritis patients can be used as diagnostic tools, and plasma or MSCs-derived extracellular vesicles can be used as a therapeutic target for arthritis. Biomimetic systems guide the nanomedicines to the targeted site by hiding them from the surveillance of the immune system. Nanomedicines can be functionalized using targeted ligand and stimuli-responsive systems to reinforce their efficacy and minimize off-target effects. This review expounds on various biomimetic systems and their functionalization for the therapeutic targets of arthritis treatment, and discusses the challenges for the clinical translation of the biomimetic system.

Effective and Targeted Human Orthotopic Glioblastoma Xenograft Therapy via a Multifunctional Biomimetic Nanomedicine

Adv. Mater. 2018, 30, 1803717 DOI: 10.1002/adma.201803717 Errors were found in Figure S9 in the Supporting Information of the published article, where duplicate staining images had been included in some of the panels of the figure. The corrected figure is shown below. The following images have been replaced: Heart IV; Kidney II. The authors sincerely apologize for any inconvenience.

Thrombus-specific/responsive biomimetic nanomedicine for spatiotemporal thrombolysis and alleviation of myocardial ischemia/reperfusion injury

Acute myocardial infarction (AMI) is usually caused by coronary thrombosis. However, the short half-life, lack of targetability and inevitable ischemia/reperfusion injury secondary to revascularization, which characterizes tissue plasminogen activator (tPA) limit its thrombolytic efficacy for AMI. To address the targeted and site-specific delivery of tPA, the current study reports the construction of a thrombus-targeting and responsive biomimetic nanoparticle (PTPN) for spatiotemporal treatment of AMI. PTPN was constituted by the thrombus microenvironment- responsive phenylboronic acid (PBA) nanocarrier, antioxidant molecular protocatechualdehyde (PC) and tPA with thrombolytic effect, which were enclosed by the platelet membrane. The thrombus-targeting capability of the platelet membrane enabled the adhesion of PTPN to damaged endothelial cells. The nanoparticle disintegrated under slightly acid condition and re-opened the infarct-related artery during the period of ischemia. Sequentially, ROS induced by blood reperfusion was eliminated by PC released from particle disintegration, and the cardiomyocyte mitochondrial function was protected from reperfusion injury. Therefore, this thrombus-specific/responsive biomimetic nanomedicine provides a spatiotemporal paradigm for AMI treatment with promising clinical translation prospects.

Copper-Based Metal-Organic Framework Induces NO Generation for Synergistic Tumor Therapy and Antimetastasis Activity.

The interaction between platelets and circulating tumor cells (CTCs) contributes to distal tumor metastasis by protecting CTCs from immunological assault and shear stress, which can be disrupted by nitric oxide (NO) through inhibiting platelet-mediated adhesion. To eradicate primitive tumors and inhibit CTC-based pulmonary metastasis, a novel biomimetic nanomedicine (mCuMNO) is designed by encapsulating Cu+ -responsive S-nitrosoglutathione as a NO donor into a copper-based metal-organic framework (CuM). This work discovers that mCuMNO can target tumor regions and deplete local glutathione (GSH) to reduce Cu2+ to Cu+ , followed by triggering NO release and hydroxyl radicals (·OH) production, thereby interrupting platelet/CTC interplay and contributing to chemodynamic therapy. Detailed studies demonstrate that mCuMNO exhibits high efficiency and safety in tumor therapy and antimetastasis activity, sheding new light on the development of CuM-based tumor synthetic therapy.

Preparation of C6 cell membrane-coated doxorubicin conjugated manganese dioxide nanoparticles and its targeted therapy application in glioma

In this study, we prepared a C6 cell membrane-coated doxorubicin conjugated manganese dioxide biomimetic nanomedicine system (MnO2-DOX-C6) for the treatment of glioma. In the glioma microenvironment, manganese dioxide could alleviate tumor hypoxia by promoting the decomposition of hydrogen peroxide (H2O2) to generate oxygen and, through a Fenton-like reaction, increase ROS levels in tumor cells, thus inducing oxidative stress to further kill cancer cells. Doxorubicin and manganese dioxide were connected through a hydrazone bond so that doxorubicin could be released only in the acidic environment of the tumor, which helped to reduce the toxicity and side effects of doxorubicin. Encapsulation of glioma C6 cancer cell membrane in MnO2-DOX-C6 made MnO2-DOX possess the homologous targeting ability and also regulated drug release rate. In vitro release experiments showed that the cumulative release of doxorubicin from MnO2-DOX-C6 at a pH of 5.0 for 48 h was 66.84 ± 3.81%, proving that it had pH sensitivity and a sustained-release effect. Cellular uptake experiments showed that MnO2-DOX-C6 had a good ability to target syngeneic tumor cells. MTT, flow cytometry, Western blot, cell immunofluorescence staining and in vivo antitumor experiments demonstrated that MnO2-DOX-C6 could promote C6 cell apoptosis and inhibit its proliferative ability. These results clearly suggested that MnO2-DOX-C6 may be a promising bionic nanosystem agent for the treatment of glioma.

Brain‐Targeting Metastatic Tumor Cell Membrane Cloaked Biomimetic Nanomedicines Mediate Potent Chemodynamic and RNAi Combinational Therapy of Glioblastoma

AbstractThe complex genetic heterogeneity of glioblastoma (GBM) together with the existence of blood brain barrier (BBB) renders GBM essentially incurable. In this paper, a brain‐targeting metastatic tumor cell membrane cloaked biomimetic nanomedicine that potently induces cascade chemodynamic and RNA interference (RNAi) is developed for combinational GBM therapy. The designed nanomedicines are constructed from metastatic melanoma cell membrane, charge‐conversional middle layer, and siRNA complexed polyethyleneimine xanthate (PEX). PEX chelates the abundant copper ions in tumor cells and then reacts with intracellular glutathione (GSH), resulting in GSH depletion and the reduction of Cu2+ to Cu+, followed by reacting with H2O2 and producing •OH via Fenton‐like reaction. Interestingly, the acidic conditions in endo/lysosomes accelerate siRNA release, inducing potent gene silencing of the anti‐apoptotic B‐cell lymphoma 2 (Bcl‐2), lead to multiple molecular cascades that readily induces GBM cell apoptosis. The results also demonstrate that this nanomedicine exhibits efficient BBB penetration via decreasing the tightness and interacting with the adhesion molecules in endothelial cells. More importantly, improved therapeutic efficacy with extended survival rates are achieved in both local melanoma and orthotopic GBM tumor models, suggesting that the chemodynamic and gene combinatorial therapy mediated by the biomimetic nanomedicines shows promising potential in treating GBM and brain metastases.

A Biomimetic Nanomedicine Targets Orthotopic Glioblastoma by Combinatorial Co‐Delivery of Temozolomide and a Methylguanine‐DNA Methyltransferase Inhibitor

AbstractGlioblastoma (GBM) is the most aggressive intracranial tumor that occurs in the central nervous system (CNS) and has no effective treatment due to the fact of drug resistance. To combat drug resistance, TMZ is generally administrated in combination with other chemotherapeutic drugs. Unfortunately, drug combinations used to date only show modest improvements in anti‐tumor effects and have increased toxicity. Herein, an ApoE peptide decorated GBM cancer cell membrane camouflaged nanomedicine (AMNPs@TMZ+LM) to specifically co‐deliver TMZ and the MGMT inhibitor lomeguatrib (LM) for combinatorial GBM treatment is developed. Incorporation of LM not only effectively suppresses the repair of damaged DNA, but also inhibits tumor cell proliferation by inducing cell cycle arrest. Importantly, this biomimetic nanomedicine achieves high BBB penetration and enhances sensitivity to both TMZ‐resistant (U251‐TR) and GBM stem cells (GSCs). Notably, AMNPs@TMZ+LM results in significant inhibition of the growth of orthotopically implanted U251‐TR tumor in mice. In comparison, treatment with single drug loaded nanomedicines results in compromised anti‐GBM effects. Histological analyses and blood parameter studies show good biocompatibility of the nanomedicine. Hence, this biomimetic nanomedicine provides a potential new approach to overcome the limitations of current GBM chemotherapy regimens by co‐delivery of TMZ and the MGMT inhibitor LM.

Erythrocyte Membrane-Enveloped Salvianolic Acid B Nanoparticles Attenuate Cerebral Ischemia-Reperfusion Injury.

PurposeIschemic stroke is the second leading cause of death and the third leading cause of disability worldwide. Salvianolic acid B (SAB), a water-soluble phenolic acid derived from the traditional Chinese medicine Salvia miltiorrhiza, exerted protective effects on cerebral ischemia-reperfusion injury. However, the efficacy of SAB is seriously hindered by poor blood brain barrier (BBB) permeability and short biological half-life in plasma. Brain targeted biomimetic nanoparticle delivery systems offer much promise in overcoming these limitations.MethodsA brain targeted biomimetic nanomedicine (RR@SABNPs) was developed, which comprised of SAB loaded bovine serum albumin nanoparticles and functionalized red blood cell membrane (RBCM) with Arg-Gly-Asp (RGD). The characterization parameters, including particle size, zeta potential, morphology, Encapsulation Efficiency (EE), Drug Loading (DL), release behavior, stability, and biocompatibility, were investigated. Moreover, the middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was used to assess the therapeutic efficacy of RR@SABNPs on ischemic stroke. Finally, the reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were detected by DHE and JC‑1 staining in oxygen-glucose deprivation/reperfusion (OGD/R) and H2O2 injured PC12 cells.ResultsRR@SABNPs exhibited spheric morphology with core-shell structures and good stability and biocompatibility. Meanwhile, RR@SABNPs can significantly prolong SAB circulation time by overcoming the reticuloendothelial system (RES) and actively targeting ischemic BBB. Moreover, RR@SABNPs had comprehensive protective effects on MCAO/R model mice, manifested as a reduced infarct volume and improved neurological and sensorimotor functions, and significantly scavenged excess ROS and maintained MMP.ConclusionThe designed brain targeted biomimetic nanomedicine RR@SABNPs can significantly prolong the half-time of SAB, deliver SAB into the ischemic brain and exhibit good therapeutic effects on MCAO/R model mice.

Brain co-delivery of first-line chemotherapy drug and epigenetic bromodomain inhibitor for multidimensional enhanced synergistic glioblastoma therapy.

Glioblastoma (GBM) is a central nervous system tumor with poor prognosis due to the rapid development of resistance to mono chemotherapy and poor brain targeted delivery. Chemoimmunotherapy (CIT) combines chemotherapy drugs with activators of innate immunity that hold great promise for GBM synergistic therapy. Herein, we chose temozolomide, TMZ, and the epigenetic bromodomain inhibitor, OTX015, and further co-encapsulated them within our well-established erythrocyte membrane camouflaged nanoparticle to yield ApoE peptide decorated biomimetic nanomedicine (ABNM@TMZ/OTX). Our nanoplatform successfully addressed the limitations in brain-targeted drug co-delivery, and simultaneously achieved multidimensional enhanced GBM synergistic CIT. In mice bearing orthotopic GL261 GBM, treatment with ABNM@TMZ/OTX resulted in marked tumor inhibition and greatly extended survival time with little side effects. The pronounced GBM treatment efficacy can be ascribed to three key factors: (i) improved nanoparticle-mediated GBM targeting delivery of therapeutic agents by greatly enhanced blood circulation time and blood-brain barrier penetration; (ii) inhibited cellular DNA repair and enhanced TMZ sensitivity to tumor cells; (iii) enhanced anti-tumor immune responses by inducing immunogenic cell death and inhibiting PD-1/PD-L1 conjugation leading to enhanced expression of CD4+ and CD8+ T cells. The study validated a biomimetic nanomedicine to yield a potential new treatment for GBM.

Photo-responsive NIR-II biomimetic nanomedicine for efficient cancer-targeted theranostics

In pancreatic cancer, the special barrier system formed by a large number of stromal cells severely hinders drug penetration in deep tumor tissues, resulting in low treatment efficiency. Cell membrane protein-camouflaged liposomal nanomedicines have cancer cell targeting abilities, whereas near-infrared two-zone (NIR-II) fluorescence imaging can achieve deep tissue penetration due to its long light wavelength (1,000–1,700 nm). To combine the cell membrane-based biomimetic technology with NIR-II fluorescence imaging, we constructed a biomimetic nanomedicine (BLIPO-I/D) by camouflaging indocyanine green-doxorubicin (ICG-DOX) liposomes with SW1990 pancreatic cancer cell membrane. The nanomedicine exhibited light-controlled DOX release and high pancreatic cancer treatment efficiency in vitro and in vivo. BLIPO-I/D showed the ability of targeted delivery of a large number of liposomes to pancreatic tumor tissues through homologous targeting of SW1990 cell membranes, which increased the NIR-II fluorescence imaging intensity. Irradiation of the liposomes taken up by pancreatic tumor tissues with near-infrared light (808 nm) triggered the rapid release of DOX from the liposomes, induced the photothermal and photodynamic effects of ICG, which exerted anti-tumor effects. Therefore, the fabricated biomimetic liposomal nanomedicine BLIPO-I/D is expected to achieve precise theranostics of pancreatic cancer.

Brain-Targeted Codelivery of Bcl-2/Bcl-xl and Mcl-1 Inhibitors by Biomimetic Nanoparticles for Orthotopic Glioblastoma Therapy.

Glioblastoma (GBM) is among the most treatment-resistant solid tumors and often recurrs after resection. One of the mechanisms through which GBM escapes various treatment modalities is the overexpression of anti-apoptotic Bcl-2 family proteins (e.g., Bcl-2, Bcl-xl, and Mcl-1) in tumor cells. Small-molecule inhibitors such as ABT-263 (ABT), which can promote mitochondrial-mediated cell apoptosis by selectively inhibiting the function of Bcl-2 and Bcl-xl, have been proven to be promising anticancer agents in clinical trials. However, the therapeutic prospects of ABT for GBM treatment are hampered by its limited blood-brain barrier (BBB) penetration, dose-dependent thrombocytopenia, and the drug resistance driven by Mcl-1, which is overexpressed in GBM cells and further upregulated upon treatment with ABT. Herein, we reported that the Mcl-1-specific inhibitor A-1210477 (A12) can act synergistically with ABT to induce potent cell apoptosis in U87 MG cells, drug-resistant U251 cells, and patient-derived GBM cancer stem cells. We further designed a biomimetic nanomedicine, based on the apolipoprotein E (ApoE) peptide-decorated red blood cell membrane and pH-sensitive dextran nanoparticles, for the brain-targeted delivery of ABT and A12. The synergistic anti-GBM effect was retained after encapsulation in the nanomedicine. Additionally, the obtained nanomedicine possessed good biocompatibility, exhibited efficient BBB penetration, and could effectively suppress tumor growth and prolong the survival time of mice bearing orthotopic GBM xenografts without inducing detectable adverse effects.

Biomimetic Nanomedicine-Triggered in Situ Vaccination for Innate and Adaptive Immunity Activations for Bacterial Osteomyelitis Treatment.

The development of bacterial vaccines for inducing an immunoresponse against infectious diseases such as osteomyelitis is of great significance and importance. However, the responsiveness of bacterial immunotherapy remains far from being satisfactory, largely due to the erratic antigen epitopes of bacteria. Herein, we report an in situ vaccination strategy for the immunotherapy of bacterial infection based on an osteomyelitis model using a biomimetic nanomedicine named as HMMP, which was constructed by engineering PpIX-encapsulated hollow MnOx with a hybrid membrane exfoliated from both macrophage and tumor cell lines. The as-established HMMP features a burst bacterial antigen release as the in situ vaccine by the augmented sonodynamic treatment and the resultant priming of antigen-presenting cells for the following activations of both cellular and humoral adaptive immunities against bacterial infections. This treatment regimen not only triggers initial bacterial regression in the established osteomyelitis model but also simultaneously generates robust systemic antibacterial immunity against poorly immunogenic secondary osteomyelitis in the contralateral knee and additionally confers long-lasting bacteria-specific immune memory responses to prevent infection relapse. Thus, our study provides a proof of concept of in situ vaccination for the activation of both innate and adaptive antibacterial immune responses, providing an individual-independent bacterial immunotherapy.

Neutrophil membrane-mimicking nanodecoys with intrinsic anti-inflammatory properties alleviate sepsis-induced acute liver injury and lethality in a mouse endotoxemia model.

Sepsis-induced acute liver injury often develops in the early stages of sepsis and can exacerbate the pathology by contributing to multiple organ dysfunction and increasing lethality. No specific therapies for sepsis-induced liver injury are currently available; therefore, effective countermeasures are urgently needed. Considering the crucial role of neutrophils in sepsis-induced liver injury, herein, neutrophil membrane-mimicking nanodecoys (NM) were explored as a biomimetic nanomedicine for the treatment of sepsis-associated liver injury. NM administration exhibited excellent biocompatibility and dramatically decreased the plasma levels of inflammatory cytokines and liver injury biomarkers, including aspartate aminotransferase, alanine aminotransferase, and direct bilirubin, in a sepsis mouse model. NM treatment also reduced hepatic malondialdehyde content, myeloperoxidase activity, and histological injury, and ultimately improved survival in the septic mice. Further in vitro studies showed that NM treatment neutralized the neutrophil chemokines and inflammatory mediators and directly mitigated neutrophil chemotaxis and adhesion. Additionally, NM also markedly weakened lipopolysaccharide-induced reactive oxygen species generation, cyclooxygenase-2 expression, nitric oxide secretion, and subsequent hepatocyte injury. Thus, this study provides a promising therapeutic strategy for the management of sepsis-induced acute liver injury.

Engineered a dual-targeting biomimetic nanomedicine for pancreatic cancer chemoimmunotherapy

The therapeutic effect of chemotherapeutics such as gemcitabine against pancreatic cancer is considerably attenuated by immune-suppressive tumor microenvironment. Improvement of chemotherapeutic efficacy by targeting tumor-associated macrophage and reprograming tumor microenvironment to enhance their efficacy may become a promising strategy. To this end, we developed a biomimetic dual-targeting nanomedicine (PG@KMCM) where gemcitabine-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles are coated with a layer of bioengineered cancer cell membrane that stably expresses peptides targeting M2-like macrophages (M2pep) while reserving tumor-associated antigens (TAAs). The PG@KMCM nanomedicine enables the simultaneous targeted delivery of gemcitabine to pancreatic tumor sites and TAMs to potentiate its therapeutic effects. Furthermore, the combination of an immune checkpoint inhibitor (PD-L1 antibody) with PG@KMCM synergistically enhanced the anti-tumoral effect by reprogramming the immune-suppressive tumor microenvironment, including the elimination of PD-L1-positive macrophages and the downregulation of PD-L1 expression. Our study proved dual-targeting PG@KMCM nanomedicine in combination with PD-L1 immune checkpoint inhibitor therapy is able to effectively reprogram the tumor microenvironment and kill pancreatic cancer cells to enhance overall therapeutic potential.Graphical

A novel biomimetic nanomedicine system with anti-inflammatory and anti-osteoporosis effects improves the therapy efficacy of steroid-resistant nephrotic syndrome

Clinically, steroid-resistant nephrotic syndrome (SRNS) is always prolonged and difficult to treat and easily develops into end-stage renal disease, resulting in a low survival rate. Strategies to reverse steroid resistance and reduce the long-term use of high doses of steroid medicines are urgently needed. In this study, a novel nanoparticle drug system (Pm-GCH) with a core–shell structure was designed. Metal–organic frameworks, synthesized by glycyrrhizic acid (G) and calcium ions (Ca2+) loaded with hydrocortisone (H) were the core of the nanoparticles. Platelet membrane vesicles were the shells. The natural platelet membrane endows Pm-GCH with good biocompatibility and the ability to promote immune escape. In addition, under the chemotaxis of inflammatory factors, platelet membranes assist Pm-GCH in nonspecific targeting of the inflammatory sites of the kidney. Under an inflammatory acid environment, GCH slowly degrades and releases glycyrrhizic acid and hydrocortisone. Glycyrrhizic acid inhibits the inactivation of hydrocortisone, jointly inhibits the activity of phospholipase A2 (PLA2) and the classic activation pathway of complement C2, blocks the production of inflammatory factors, plays an anti-inflammatory role, and enhances the efficacy of hydrocortisone in the treatment of SRNS. Moreover, glycyrrhizic acid alleviates osteoporosis induced by long-term use of glucocorticoids. These results indicate that Pm-GCH is a promising treatment strategy for SRNS.Graphical