Biomimetic Delivery System Research Articles

Immunocyte membrane-derived biomimetic nano-drug delivery system: a pioneering platform for tumour immunotherapy.

Tumor immunotherapy characterized by its high specificity and minimal side effects has achieved revolutionary progress in the field of cancer treatment. However, the complex mechanisms of tumor immune microenvironment (TIME) and the individual variability of patients' immune system still present significant challenges to its clinical application. Immunocyte membrane-coated nanocarrier systems, as an innovative biomimetic drug delivery platform, exhibit remarkable advantages in tumor immunotherapy due to their high targeting capability, good biocompatibility and low immunogenicity. In this review we summarize the latest research advances in biomimetic delivery systems based on immune cells for tumor immunotherapy. We outline the existing methods of tumor immunotherapy including immune checkpoint therapy, adoptive cell transfer therapy and cancer vaccines etc. with a focus on the application of various immunocyte membranes in tumor immunotherapy and their prospects and challenges in drug delivery and immune modulation. We look forward to further exploring the application of biomimetic delivery systems based on immunocyte membrane-coated nanoparticles, aiming to provide a new framework for the clinical treatment of tumor immunity.

Enhanced breast cancer treatment using phototherapy and RNS therapy with macrophage membrane-coated liposomes

Breast cancer, the predominant malignancy afflicting women, continues to pose formidable challenges despite advancements in therapeutic interventions. This study elucidates the potential of phototherapy, comprising both photothermal and photodynamic therapy (PTT/PDT), as a novel and promising modality. To achieve this goal, we devised liposomes coated with macrophage cell membranes including macrophage-associated membrane proteins, which have demonstrated promise in biomimetic delivery systems for targeting tumors while preserving their inherent tumor-homing capabilities. This integrated biomimetic delivery system comprised IR780, NONOate, and perfluorocarbon. This strategic encapsulation aims to achieve a synergistic combination of photodynamic therapy (PDT) and reactive nitrogen species (RNS) therapy. Under near-infrared laser irradiation at 808 nm, IR780 demonstrates its ability to prolifically generate reactive oxygen species (ROS), including superoxide anion (O2•−), singlet oxygen, and hydroxyl radical (·OH). Simultaneously, NONOate releases nitric oxide (NO) gas upon the same laser irradiation, thereby engaging with IR780-induced ROS to facilitate the formation of peroxynitrite anion (ONOO−), ultimately inducing programmed cell death in cancer cells. Additionally, the perfluorocarbon component of our delivery system exhibits a notable affinity for oxygen and demonstrates efficient oxygen-carrying capabilities. Our results demonstrate that IR780-NO-PFH-Lip@M significantly enhances breast cancer cell toxicity, reducing proliferation and in vivo tumor growth through simultaneous heat, ROS, and RNS production. This study contributes valuable insights to the ongoing discourse on innovative strategies for advancing cancer therapeutics.

Biomimetic MicroRNAs-Selenium-Nanocomposites for Targeted and Combined Hyperlipidemia Therapy.

Hyperlipidemia is considered as a high-risk factor for leading to coronary heart disease. MicroRNA-148a-3p (miR-148a-3p) inhibitor is a potential therapeutic target to bind low-density lipoprotein cholesterol receptors (LDLR) for decreasing the levels of low-density lipoprotein cholesterol in plasma. However, the therapeutic effects are not ideal in the clinical translation of nucleic acids treatment, owing to the short circulation time in vivo. Therefore, a platelet membrane (PM) cloaks Se nanoparticles (SeNPs) delivery system with chitosan (CS) modifies and miR-148a-3p inhibitors encapsulated is designed (PM/CS-SeNPs/miR). The PM/CS-SeNPs/miR shows a uniform shell-core structure with a particle size of ≈90 nm. Co-delivering miR-148a-3p inhibitors and Se effectively alleviate hyperlipidemia via LDLR pathway and Toll-Like Receptor 4 (TLR-4)/NF-κB signaling pathway, respectively. Furthermore, coated by PM, PM/CS-SeNPs/miR successfully prolong circulation time to 48 h in vivo and quickly target to liver with no toxicity. This dual combination therapy with miRNAs and Se based on nanoparticles targeted delivery presents a high-performance strategy for precise hyperlipidemia treatment.

HepG2 exosomes coated luteolin nanoparticles remodeling hepatic stellate cells and combination with sorafenib for the treatment of hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and recurrence rate. The efficacy of the first-line drug sorafenib is impeded by drug resistance, which is closely related to activated hepatic stellate cells (HSCs). The natural product luteolin is good at alleviating the activation of HSC. However, its clinical application is limited to poor solubility, bioavailability and lacking of HSCs targeting effects. This study aims to construct luteolin-loaded biomimetic nanoparticles based on HepG2 exosomes for targeting HSCs and enhancing the therapeutic effects of sorafenib on HCC.MethodsThe HepG2 exosomes extracted were identified by size distribution, Zeta potential and characteristic proteins. Luteolin-loaded polylactic acid-glycolic acid (PLGA) nanoparticles (Lut-NPs) were prepared and wrapped by HepG2 exosomes to form biomimetic nanoparticles (Exo-Lut-NPs). A HepG2 cell sorafenib-resistant model induced by LX2 cell conditioned medium (CM) was established to evaluate the effects of Exo-Lut-NPs on reversing sorafenib-resistant in vitro. And the combined therapeutic effects of Exo-Lut-NPs with sorafenib were evaluated on a HepG2/LX2 subcutaneous xenograft tumor model in vivo.ResultsThe particle size, drug loading capacity and encapsulation efficiency of Exo-Lut-NPs were 165 ± 10 nm, 2.6 ± 0.2% and 56.9 ± 4.3%, respectively. The in vitro HepG2 sorafenib-resistant model was induced by the CM of LX2 cells, and the results showed that Exo-Lut-NPs partially reversed the sorafenib resistance of HepG2 cells by affecting the CM of LX2 cells. The combined therapy of Exo-Lut-NPs with sorafenib markedly suppressed tumor growth in a HepG2/LX2 subcutaneous xenograft tumor model.ConclusionsThis study suggests that the Exo-Lut-NP is a novel and promising biomimetic delivery system which can combine with sorafenib for HCC therapy.

Blocking tumor-platelet crosstalk to prevent tumor metastasis via reprograming glycolysis using biomimetic membrane-hybridized liposomes

Activated platelets promote tumor progression and metastasis through active interactions with cancer cells, especially in promoting epithelial-mesenchymal transition (EMT) of tumor cells and shedding tumor cells into the blood. Blocking platelet-tumor cell interactions can be a potential strategy to inhibit tumor metastasis. Platelet activation requires energy produced from aerobic glycolysis. Based on this, we propose a platelet suppression strategy by reprogramming glucose metabolism of platelets, which has an advantage over conventional antiplatelet treatment that has a risk of serious hemorrhage. We develop a biomimetic delivery system using platelet membrane-hybridized liposomes (PM-Lipo) for codelivery of quercetin and shikonin to simultaneously inhibit lactate transporter MCT-4 and a glycolytic enzyme PKM2 for achieving metabolic reprogramming of platelets and suppressing platelet activation. Notably, PM-Lipo can also inhibit glycolysis in cancer cells, which actually takes “two-birds-one-stone” action. Consequently, the platelet-tumor cell interactions are inhibited. Moreover, PM-Lipo can bind with circulating tumor cells and reduce their seeding in the premetastatic microenvironment. The in vivo studies further demonstrated that PM-Lipo can effectively suppress primary tumor growth and reduce lung metastasis without affecting inherited functions of platelets. Reprogramming glycolysis of platelets can remodel the tumor immune microenvironment, including suppression of Treg and stimulation of CTLs.

Triptolide‐Loaded Mesenchymal Stem Cell–Derived Exosomes Ameliorates Lipopolysaccharide‐Induced Acute Lung Injury via Induction of Nrf‐2/HO‐1 Signaling Pathway–Dependent Autophagy and Mitigation of MAPK Signaling Pathway

Acute lung injury (ALI) is a severe disease characterized by a pulmonary inflammatory response and oxidative stress. Triptolide has been demonstrated to have anti‐inflammatory and antioxidant properties. Herein, we present triptolide‐loaded mesenchymal stem cell–derived exosomes (MSC‐Exos) as a multifunctional biomimetic delivery system (Tri‐Exos) for targeting injured lung tissue. The therapeutic effect of Tri‐Exos on ALI was evaluated by measuring inflammatory cytokines content, the expression of myeloperoxidase (MPO), the number of immune cells in bronchoalveolar lavage fluid, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity. Subsequently, immunohistochemistry and Western blotting were used to assess the expression levels of critical proteins in the nuclear factor erythroid 2‐related factor 2 (Nrf‐2) signaling pathway, autophagy pathway, apoptosis, and MAPK signaling pathway. The experimental results showed that LPS significantly increased pathological damage, secretion of inflammatory cytokines, and oxidative stress in lung tissue. However, treatment with Tri‐Exos significantly alleviated this series of pathological changes. Tri‐Exos significantly upregulated the expression of Nrf‐2 signaling pathway–related proteins, autophagy, and apoptosis and inhibited the expression of MAPK signaling pathway‐related proteins in the ALI model. Our study showed that Tri‐Exos exerted a therapeutic effect on LPS‐induced ALI by regulating the Nrf‐2 signaling pathway–dependent autophagy and MAPK signaling pathway.

Translational Challenges and Prospective Solutions in the Implementation of Biomimetic Delivery Systems.

Biomimetic delivery systems (BDSs), inspired by the intricate designs of biological systems, have emerged as a groundbreaking paradigm in nanomedicine, offering unparalleled advantages in therapeutic delivery. These systems, encompassing platforms such as liposomes, protein-based nanoparticles, extracellular vesicles, and polysaccharides, are lauded for their targeted delivery, minimized side effects, and enhanced therapeutic outcomes. However, the translation of BDSs from research settings to clinical applications is fraught with challenges, including reproducibility concerns, physiological stability, and rigorous efficacy and safety evaluations. Furthermore, the innovative nature of BDSs demands the reevaluation and evolution of existing regulatory and ethical frameworks. This review provides an overview of BDSs and delves into the multifaceted translational challenges and present emerging solutions, underscored by real-world case studies. Emphasizing the potential of BDSs to redefine healthcare, we advocate for sustained interdisciplinary collaboration and research. As our understanding of biological systems deepens, the future of BDSs in clinical translation appears promising, with a focus on personalized medicine and refined patient-specific delivery systems.

Diethylaminoethyl-dextran and monocyte cell membrane coated 1,8-cineole delivery system for intracellular delivery and synergistic treatment of atherosclerosis

We have developed a biomimetic delivery system termed the Monocyte Cell Membrane-Coated 1,8-Cineole Biomimetic Delivery System (MM-CIN-BDS or BDS), which integrates diethylaminoethyl-dextran (DEAE) and monocyte cell membrane (MM). This innovative approach enhances the cellular uptake efficiency of 1,8-cineole (CIN) and facilitates targeted therapy for atherosclerosis. Our findings demonstrate the successful modification of the drug carrier with DEAE and MM, as validated by measurements of particle size, zeta potential, microscopic morphology, and western blotting analyses. Notably, cellular uptake experiments unveil a significant enhancement in cellular uptake efficiency due to DEAE modification. However, the introduction of monocyte cell membranes diminishes this effect in normal human umbilical vein endothelial cells (HUVECs), although this efficiency is notably restored in HUVECs activated with lipopolysaccharide (LPS). Through in vivo imaging investigations, we observe that the MM coating augments distribution in the spleen, brain, and atherosclerotic plaques, while concurrently diminishing distribution in the heart and kidneys. Animal studies corroborate these findings, illustrating that MM-CIN-BDS treatment curtails lipid parameters, dampens the expression of inflammatory factors and proteins, mitigates vascular tissue damage, and ultimately reduces the extent of atherosclerotic lesion areas. To encapsulate, DEAE emerges as an especially adept agent for modifying drug carriers with suboptimal cellular uptake efficiency in the realm of cardiovascular diseases. The potential therapeutic promise of MM-CIN-BDS for atherosclerosis treatment is evident from our research.

Graphene quantum dots-loaded macrophages as a biomimetic delivery system for bioimaging and photodynamic therapy

Macrophages have been recommended for site-specific tumoral delivery of genes, drugs, or nanoparticles. Graphene quantum dots (GQDs) are a well-known fluorescence-based diagnosis and photodynamic therapy (PDT) agent. Herein, we determined the therapeutic efficacy of hybrid GQD-loaded macrophages in a 3D culture model and a xenograft mouse model of human lung cancer cells. We examined the PDT efficacy of hybrid GQD-loaded macrophages in both models using LED light. Cell viability assay showed that the LED light-based PDT induced cell death via GQDs. Reactive oxygen species and Ca2+ detection assays indicated that GQD-loaded macrophages induced apoptosis in the in vitro 3D culture model. In vivo fluorescence bioimaging and ex vivo fluorescence images of major organs (the kidney, liver, lung, spleen, and tumor) revealed a tumor-homing effect of GQD-loaded macrophages in the xenograft mouse model. Our results demonstrated that hybrid GQD-loaded macrophages are a promising biomimetic delivery system for bioimaging and cancer therapy.

A novel oral biomimetic delivery system enhancing both the mucosal and systemic immunity of influenza virus vaccine

Oral vaccines hold great promise for preventing major infectious diseases, but their development is limited by various gastrointestinal tract (GIT) barriers and the low proportion of intestinal microfold (M) cells. Here, inspired by the specific absorption pathway of dietary fat, a novel bionic intestinal lymphatic delivery system based on large mesoporous silica nanoparticles (LMSN) was developed for oral delivery of H1N1 influenza split vaccine (SV). Encouragingly, LMSN with triglyceride biomimetic structure and encapsulated by double-end palmitic acid esterified PEG (PEG-DP), namely TGLMSN@PEG-DP, exhibited high intestinal epithelium permeability and excellent lymphatic targeting ability. Additionally, TGLMSN, which acting as both antigen carrier and adjuvant, significantly enhanced the ability of SV to stimulate dendritic cells maturation. The results demonstrated that TGLMSN@PEG-DP vigorously augmented SV-induced antigen-specific systemic and mucosal immunity, compared to oral SV alone. To our knowledge, this is the first study to customize mesoporous silica nanocarriers to load SV and deliver vaccines to mesenteric lymph nodes (MLNs) mainly through the intestinal epithelium cells (IECs) pathway rather than M cells route alone. This work will not only improve the existing influenza vaccination methods, but also open up a new avenue for the design of vaccines against pathogens infected via mucosal route.

Neutrophil membrane biomimetic delivery system (Ptdser-NM-Lipo/Fer-1) designed for targeting atherosclerosis therapy.

Atherosclerosis is a progressive inflammatory disease characterised by excessive lipid accumulation and inflammatory cell infiltration and is the basis of most cardiovascular diseases and peripheral arterial diseases. Therefore, an effectively targeted delivery system is urgently needed to deliver ferroptosis-specific inhibitors to the site of arterial plaque and the inflammatory microenvironment. Inspired by the fact that neutrophils can be recruited to arterial plaques under the action of adhesion molecules and chemokines, the authors developed a neutrophil membrane hybrid liposome nano-mimetic system (Ptdser-NM-Lipo/Fer-1) that delivers Ferrostatin-1 (Fer-1) to the atherosclerotic plaque effectively, which is composed of Fer-1-loaded Ptdser-modified liposomes core and neutrophils shell. Fer-1 was released at the AS plaque site to remove reactive oxygen species (ROS) and improve the inflammatory microenvironment. In vitro ROS clearance experiments have shown that 50μmol/ml Fer-1 can significantly remove ROS produced by H2 O2 -induced MOVAS cells and Ptdser-NM-Lipo/Fer-1 revealed a 3-fold increase in the inhibition rate of ROS than free Fer-1 in induced-RAW264.7, demonstrating its superior ROS-cleaning effect. Based on the interaction of adhesion molecules, such as vascular cell adhesion molecule 1, ICAM-1, P-selectin, E-selectin, and chemokines released in the inflamed site, the aorta in NM-Lipo-treated mice displayed 1.3-fold greater radiant efficiency than platelet membrane-Lipo-treated mice. Meanwhile, due to the modification of the Ptdser, the aorta in Ptdser-NM-Lipo/Fer-1-treated mice exhibited the highest fluorescence intensity, demonstrating its excellent targeting ability for atherosclerosis. Therefore, we present a specific formulation for the treatment of atherosclerosis with the potential for novel therapeutic uses.

Platelet Membrane-Fused Circulating Extracellular Vesicles Protect the Heart from Ischemia/Reperfusion Injury.

Myocardial ischemia/reperfusion injury (I/RI) may potentiate cardiac remodeling and heart failure, while effective therapies for I/RI remain lacking. Circulating human plasma-derived extracellular vesicles (hEV) have great potential to protect against I/RI. However, the effective delivery of hEV in vivo remains a limiting factor for clinical application. The present study constructs a biomimetic delivery system of platelet membrane-fused hEV (P-hEV), utilizing the natural affinity of platelets for hEV delivery to the injured vascular and myocardial sites. The results show that platelet membrane and hEV membrane fusion can be achieved through repeated extrusion. Compared to non-modified hEV, P-hEV uptake is greatly enhanced in human umbilical vein endothelial cells (HUVECs) stressed by oxygen-glucose deprivation/reperfusion (OGD/R). Functionally, P-hEV inhibits HUVECand neonatal rat cardiomyocyte(NRCM) apoptosis and promotes HUVECsmigration and tube formation under OGD/R stress in vitro. Intravenous delivery of P-hEV more effectively targets and accumulates at injury sites in the heart. Furthermore, P-hEV significantly enhances protection against acute I/RI and attenuates cardiac remodeling at three weeks post-I/RI. In conclusion, the platelet membrane-fused hEV delivery system enhances the target delivery of EV to protect against myocardial I/RI, presenting a novel drug delivery system for ischemic heart diseases.

Stimuli-responsive and biomimetic delivery systems for sepsis and related complications.

Sepsis, a consequence of an imbalanced immune response to infection, is currently one of the leading causes of death globally. Despite advances in the discoveries of potential targets and nanotechnology, sepsis still lacks effective drug delivery systems for optimal treatment. Stimuli-responsive and biomimetic nano delivery systems, specifically, are emerging as advanced bio-inspired nanocarriers for enhancing the treatment of sepsis. Herein, we present a critical review of different stimuli-responsive systems, including pH-; enzyme-; ROS- and toxin-responsive nanocarriers, reported in the delivery of therapeutics for sepsis. Biomimetic nanocarriers, utilizing natural pathways in the inflammatory cascade to optimize sepsis therapy, are also reviewed, in addition to smart, multifunctional vehicles. The review highlights the nanomaterials designed for constructing these systems; their physicochemical properties; the mechanisms of drug release; and their potential for enhancing the therapeutic efficacy of their cargo. Current challenges are identified and future avenues for research into the optimization of bio-inspired nano delivery systems for sepsis are also proposed. This review confirms the potential of stimuli-responsive and biomimetic nanocarriers for enhanced therapy against sepsis and related complications.

Platelet Membrane Cloaked Nanotubes to Accelerate Thrombolysis by Thrombus Clot-Targeting and Penetration.

Thrombotic diseases have a high rate of mortality and disability, and pose a serious threat to global public health. Currently, most thrombolytic drugs especially protein drugs have a short blood-circulation time, resulting in low thrombolytic efficiency. Therefore, a platelet membrane (Pm) cloaked nanotube (NT-RGD/Pm) biomimetic delivery system with enhanced thrombolytic efficiency is designed. Nanotubes (NT) with an excellent clot-penetration properties are used to load a protein thrombolytic drug urokinase (Uk). Platelet-targeting arginine glycine-aspartic peptide (RGD) is grafted onto the surface of the nanotubes (NT-RGD) prior to cloaking. Multiple particle tracking (MPT) technique and confocal laser scanning microscope (CLSM) analysis are applied and the results show that the nanotubes possess a strong penetration and diffusion capacity in thrombus clots. After the Pm cloaking on NT-RGD/Uk, it shows a thrombus microenvironmental responsive release property and the half-life of Uk is six times longer than that of free Uk. Most importantly, NT-RGD-Uk/Pm exhibits a 60% thrombolytic efficiency in the FeCl3 -induced thrombosis mouse model, and it is able to significantly reduce the bleeding side effects of Uk. This Pm-cloaked nanotube system is an effective and promising platform for the controlled and targeted delivery of drugs for the thrombus treatment.

A Trojan horse biomimetic delivery system using mesenchymal stem cells for HIF-1α siRNA-loaded nanoparticles on retinal pigment epithelial cells under hypoxia environment.

To demonstrate the feasibility of mesenchymal stem cell (MSC)-mediated nano drug delivery, which was characterized by the "Trojan horse"-like transport of hypoxia-inducible factor-1α small interfering RNA (HIF-1α siRNA) between MSCs and retinal pigment epithelial cells (RPE) under hypoxia environment. Plasmid and lentivirus targeting the human HIF-1α gene were designed and constructed. HIF-1α siRNA was encapsulated into poly(lactic-co-glycolic acid) nanoparticles (PLGA-NPs) through the water-in-oil-in-water (w/o/w) multiple emulsion technique. The effect of PLGA-NPs uptake on the expression of HIF-1α mRNA was tested in RPE cells by real-time quantitative polymerase chain reaction (qPCR) and additional transfected conditions were used as control, including lentivirus group, nude plasmid group and blank PLGA group. MSCs were transfected with the NPs and the transfection efficacy was evaluated by flow cytometry. Transwell co-culture system of transfected MSCs and RPE cells was constructed under hypoxia environment. The effects of MSC-loaded HIF-1α siRNA PLGA-NPs on proliferation, apoptosis, and migration of RPE cells were then evaluated. The effect of transfected MSCs on HIF-1α expression of RPE cells was analyzed by using qPCR at the time points 24h, 3d, and 7d. The average diameter of PLGA-NPs loaded with HIF siRNA was 314.1 nm and the zeta potential was -0.36 mV. The transfection efficiency of PLGA-NPs was 67.3%±5.2% into MSCs by using flow cytometry. Compared with the lentivirus group, the PLGA-NPs loaded with HIF-1α siRNA can effectively reduce the expression of HIF-1α mRNA up to 7d in RPE (0.63±0.05 at 7d, P<0.001). In the Transwell co-culture system of transfected MSCs and RPE, the abilities of proliferation (2.34±0.17, 2.40±0.28, 2.47±0.24 at 48h, F=0.23, P=0.80), apoptosis (14.83%±2.43%, 12.94%±2.19%, 12.39%±3.21%; F=0.70, P=0.53) and migration (124.5±7.78, 119.5±5.32, 130±9.89, F=1.33, P=0.33) of the RPE cells had no differences between MSC-loaded HIF-1α siRNA PLGA-NPs and other groups. The inhibition of PLGA on the HIF-1α mRNA expression in RPE cells could continue until the 7th day, the level of HIF-1α mRNA was lower than that of other groups (F=171.98, P<0.001). The delivery of PLGA-NPs loaded with HIF-1α siRNA carried by MSCs is found to be beneficial temporally for HIF-1α mRNA inhibition in RPE cells under hypoxia environment. The MSC-based bio-mimetic delivery of HIF-1α siRNA nanoparticles is a potential method for therapy against choroidal neovascularization.

Liposome‐Mediated Biomimetic Delivery of PLK3 Inhibitor with NIR II‐Triggered Release Prevents Renal Ischemia‐Reperfusion Injury

AbstractAs one of the leading causes of acute kidney injury (AKI), ischemia‐reperfusion injury (IRI) results in tubular necrosis and renal inflammation. Here, from gene screening, it is found that Polo‐like kinase 3 (PLK3), but not other PLKs, is highly up‐regulated during mouse IRI. In vivo administration of PLK3 inhibitor alleviates IRI‐induced AKI, but induces myelosuppression. Thus, a novel liposome‐mediated biomimetic delivery system with 1080 nm near infrared (NIR)‐triggered release to specifically and efficiently delivering the inhibitor to the kidney is developed. NIR light irradiation to kidney results in an excellent effect for reduced immune cell infiltration and renal inflammation. Mechanistically, PLK3 inhibition suppresses the degradation of hypoxia‐inducible factor‐1α (HIF‐1α) and reactive oxygen species (ROS)‐mediated oxidative stress, thus protecting the renal tubular epithelial cells from cell death and preventing macrophage activation and renal inflammation. Thus, the NIR light‐triggered liposome system provides an efficient candidate treatment for AKI without systemic side effect.

A tumor cell membrane-coated self-amplified nanosystem as a nanovaccine to boost the therapeutic effect of anti-PD-L1 antibody.

To improve the response rate of immune checkpoint inhibitors such as anti-PD-L1 antibody in immunosuppressive cancers like triple-negative breast cancer (TNBC), induction of immunogenic cell death (ICD) at tumor sites can increase the antigenicity and adjuvanticity to activate the immune microenvironment so that tumors become sensitive to the intervention of immune checkpoint inhibitors. Herein, a self-amplified biomimetic nanosystem, mEHGZ, was constructed by encapsulation of epirubicin (EPI), glucose oxidase (Gox) and hemin in ZIF-8 nanoparticles and coating of the nanoparticles with calreticulin (CRT) over-expressed tumor cell membrane. EPI acts as an ICD inducer, Gox and hemin medicate the cascade generation of reactive oxygen species (ROS) to strengthen the ICD effect, and CRT-rich membrane as “eat me” signal promote presentation of the released antigens by dendritic cells (DCs) to invoke the tumor-immunity cycle. The biomimetic delivery system displays an amplified ICD effect via Gox oxidation, hydroxyl radical generation and glutathione (GSH) depletion. The induced potent ICD effect promotes DCs maturation and cytotoxic T lymphocytes (CTLs) infiltration, reversing an immunosuppressive tumor microenvironment to an immunoresponsive one. Treatment with the nanosystem in combination with anti-PD-L1 antibody results in distinctive inhibition of tumor growth and lung metastasis, supporting that a potent ICD effect can significantly boost the therapeutic efficacy of the anti-PD-L1 antibody. This self-amplified biomimetic nanoplatform offers a promising means of raising the response rate of immune checkpoint inhibitors.

The Role of Hitchhiking in Cancer Therapeutics—A Review

AbstractHitchhiking is a phenomenon of cruising on surfaces. Inspired by this process, biomimetic delivery systems leveraging the intrinsic ability of circulatory cells to target tumors exhibit considerable potential in cancer theranostics. Besides human circulatory cell‐mediated hitchhiking, bacteria‐driven hitchhiking strategies also manifest promise in cancer therapy. Such tactics are primarily built using nonpathogenic invasive bacteria with tumor homing capabilities. The chemotherapeutic cargos are hitchhiked onto the circulatory cells or bacterial spores for tumor‐targeted delivery. By integrating the benefits of such cells and therapeutic cargo, numerous efficient delivery systems that implement the notion of hitchhiking for cancer therapy are generated. Following an overview of several hitchhiking concepts, this article reviews various cellular and bacterial hitchhiking approaches for cancer treatment. Additionally, the challenges and prospects in the field of cancer theranostics related to hitchhiking are also discussed.

Biomimetic Metal-Organic Frameworks as Targeted Vehicles to Enhance Osteogenesis.

Although engineered nanoparticles loaded with specific growth factors are used to regulate differentiation of stem cells, the low loading efficiency and biocompatibility are still great challenges in tissue repair. A nature-inspired biomimetic delivery system with targeted functions is attractive for enhancing cell activity and controlling cell fate. Herein, a stem cell membrane (SCM)-wrapped dexamethasone (DEX)-loaded zeolitic imidazolate framework-8 (ZIF-8) is constructed, which integrates the synthetic nanomaterials with native plasma membrane, to achieve efficient DEX delivery and DEX-mediated bone repair. The DEX@ZIF-8-SCM enables high DEX loading capacity, modulates the sustained release, and facilitates the specific uptake of mesenchymal stem cells (MSCs), owing to the porous property of ZIF-8 and the innate targeting capability of SCM. The endocytosed DEX@ZIF-8-SCM shows high cytocompatibility and greatly enhances the osteogenic differentiation of MSCs. Furthermore, RNA-sequencing data reveal that the phosphoinositide 3-kinase (PI3K)-Akt signaling pathways are activated and dominantly involved in the accelerated osteogenesis. In the bone defect model, the administrated DEX@ZIF-8-SCM exerts excellent biocompatibility and effectively promotes bone regeneration. Overall, the SCM-derived biomimetic nanoplatform achieves targeted delivery, excellent biosafety, and enhanced osteogenic differentiation and bone repair, which provides a new and valid strategy for treating various tissue injuries.

Advancement of Biomimetic Nanoparticles for Targeted Drug Delivery

There has been an increasing requirement for more efficient and less iatrogenic therapies for drug delivery, encouraging researches to develop new vectors that ensure targeted delivery of drugs and other therapeutic agents in medicine. Traditional synthetic drug vectors which include polymer and lipid particles are not preferred for clinical applications due to their high cytotoxicity, greater immunogenicity and low cell membrane penetrability. On the other hand, natural particulates ranging from pathogens to mammalian cells are specially optimized forin vivofunctions and possess features desirable for drug delivery vectors. Biomimetics involves exploiting biological organisms, cells and molecules or deriving inspiration from them. The Biomimetic Nanoparticles have ushered a new generation of drug carriers, attracting researchers because of their excellent biocompatibility, biodistribution, low chances of recognition and removal by the immune system. Their ability to mimic the bio-structure and function of the biological system makes them reliable drug delivery vectors especially for disease targeting. The advanced biotechnology tools used for engineering synthetic and natural derived nano-systems along with better understanding of biological systems, have enabled researchers to apply these ideas to the delivery of drugs, small interfering RNA, proteins and other therapeutic agents. This review summarizes recent advances in biomimetic nanoparticles used for targeted drug delivery in medicine, obtained by processing synthetic materials using biomimetics. The challenges of biomimetic delivery systems and future directions are also discussed and proposed herein.