The Prospect of Biomimetic Immune Cell Membrane-Coated Nanomedicines for Treatment of Serious Bacterial Infections and Sepsis.

Invasive bacterial infections and sepsis are persistent global health concerns, complicated further by the escalating threat of antibiotic resistance. Over the past 40 years, collaborative endeavors to improve the diagnosis and critical care of septic patients have improved outcomes, yet grappling with the intricate immune dysfunction underlying the septic condition remains a formidable challenge. Anti-inflammatory interventions that exhibited promise in murine models failed to manifest consistent survival benefits in clinical studies through recent decades. Novel therapeutic approaches that target bacterial virulence factors, for example with monoclonal antibodies, aim to thwart pathogen-driven damage and restore an advantage to the immune system. A pioneering technology addressing this challenge is biomimetic nanoparticles-a therapeutic platform featuring nanoscale particles enveloped in natural cell membranes. Borne from the quest for a durable drug delivery system, the original red blood cell-coated nanoparticles showcased a broad capacity to absorb bacterial and environmental toxins from serum. Tailoring the membrane coating to immune cell sources imparts unique characteristics to the nanoparticles suitable for broader application in infectious disease. Their capacity to bind both inflammatory signals and virulence factors assembles the most promising sepsis therapies into a singular, pathogen-agnostic therapeutic. This review explores the ongoing work on immune cell-coated nanoparticle therapeutics for infection and sepsis. SIGNIFICANCE STATEMENT: Invasive bacterial infections and sepsis are a major global health problem made worse by expanding antibiotic resistance, meaning better treatment options are urgently needed. Biomimetic cell-membrane-coated nanoparticles are an innovative therapeutic platform that deploys a multifaceted mechanism to action to neutralize microbial virulence factors, capture endotoxins, and bind excessive host proinflammatory cytokines, seeking to reduce host tissue injury, aid in microbial clearance, and improve patient outcomes.

Cell-derived biomimetic nanoparticles for the targeted therapy of ALI/ARDS.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common clinical critical diseases with high morbidity and mortality. Especially since the COVID-19 outbreak, the mortality rates of critically ill patients with ARDS can be as high as 60%. Therefore, this problem has become a matter of concern to respiratory critical care. To date, the main clinical measures for ALI/ARDS are mechanical ventilation and drug therapy. Although ventilation treatment reduces mortality, it increases the risk of hyperxemia, and drug treatment lacks safe and effective delivery methods. Therefore, novel therapeutic strategies for ALI/ARDS are urgently needed. Developments in nanotechnology have allowed the construction of a safe, efficient, precise, and controllable drug delivery system. However, problems still encounter in the treatment of ALI/ARDS, such as the toxicity, poor targeting ability, and immunogenicity of nanomaterials. Cell-derived biomimetic nanodelivery drug systems have the advantages of low toxicity, long circulation, high targeting, and high bioavailability and show great therapeutic promises for ALI/ARDS owing to their acquired cellular biological features and some functions. This paper reviews ALI/ARDS treatments based on cell membrane biomimetic technology and extracellular vesicle biomimetic technology, aiming to achieve a significant breakthrough in ALI/ARDS treatments.

Biomimetic nanoparticles deliver mRNAs encoding costimulatory receptors and enhance T cell mediated cancer immunotherapy.

Antibodies targeting costimulatory receptors of T cells have been developed for the activation of T cell immunity in cancer immunotherapy. However, costimulatory molecule expression is often lacking in tumor-infiltrating immune cells, which can impede antibody-mediated immunotherapy. Here, we hypothesize that delivery of costimulatory receptor mRNA to tumor-infiltrating T cells will enhance the antitumor effects of antibodies. We first design a library of biomimetic nanoparticles and find that phospholipid nanoparticles (PL1) effectively deliver costimulatory receptor mRNA (CD137 or OX40) to T cells. Then, we demonstrate that the combination of PL1-OX40 mRNA and anti-OX40 antibody exhibits significantly improved antitumor activity compared to anti-OX40 antibody alone in multiple tumor models. This treatment regimen results in a 60% complete response rate in the A20 tumor model, with these mice being resistant to rechallenge by A20 tumor cells. Additionally, the combination of PL1-OX40 mRNA and anti-OX40 antibody significantly boosts the antitumor immune response to anti-PD-1 + anti-CTLA-4 antibodies in the B16F10 tumor model. This study supports the concept of delivering mRNA encoding costimulatory receptors in combination with the corresponding agonistic antibody as a strategy to enhance cancer immunotherapy.

Tumor-derived biomimetic nanozyme with immune evasion ability for synergistically enhanced low dose radiotherapy.

High doses of radiation can cause serious side effects and efficient radiosensitizers are urgently needed. To overcome this problem, we developed a biomimetic nanozyme system (CF) by coating pyrite (FeS2) into tumor-derived exosomes for enhanced low-dose radiotherapy (RT). CF system give FeS2 with immune escape and homologous targeting abilities. After administration, CF with both glutathione oxidase (GSH-OXD) and peroxidase (POD) activities can significantly lower the content of GSH in tumor tissues and catalyze intracellular hydrogen peroxide (H2O2) to produce a large amount of ·OH for intracellular redox homeostasis disruption and mitochondria destruction, thus reducing RT resistance. Experiments in vivo and in vitro showed that combining CF with RT (2 Gy) can provide a substantial suppression of tumor proliferation. This is the first attempt to use exosomes bionic FeS2 nanozyme for realizing low-dose RT, which broaden the prospects of nanozymes.

Injectable Hydrogel Capable of In Situ Covalent Crosslinking for Permanent Embolization.

Vascular embolization provides an effective approach for the treatment of hemorrhage, aneurysms, and other vascular abnormalities. However, current embolic materials, such as metallic coils and liquid embolic agents, are limited by their inability to provide safe, consistent, and controlled embolization. Here, we report an injectable hydrogel that can remain at the injection site and subsequently undergo in situ covalent crosslinking, leading to the formation of a dual-crosslinking network (DCN) hydrogel for endovascular embolization. The DCN hydrogel is simple to prepare, easy to deploy via needles and catheters, and mechanically stable at the target injection site, thereby avoiding embolization of nontarget vessels. It possesses efficient hemostatic activity and good biocompatibility. The DCN hydrogel is also clearly visible under X-ray imaging, thereby allowing for targeted embolization. In vivo tests in a rabbit artery model demonstrates that the DCN hydrogel is effective in achieving immediate embolization of the target artery with long-term occlusion by inducing luminal fibrosis. Collectively, the DCN hydrogel provides a viable, biocompatible, and cost-effective alternative to existing embolic materials with clinical translation potential for endovascular embolization.

Restoring Cardiac Functions after Myocardial Infarction-Ischemia/Reperfusion via an Exosome Anchoring Conductive Hydrogel.

Both myocardial infarction (MI) and the follow-up reperfusion will lead to an inevitable injury to myocardial tissues, such as cardiac dysfunctions, fibrosis, and reduction of intercellular cell-to-cell interactions. Recently, exosomes (Exo) derived from stem cells have demonstrated a robust capability to promote angiogenesis and tissue repair. However, the short half-life of Exo and rapid clearance lead to insufficient therapeutic doses in the lesion area. Herein, an injectable conductive hydrogel is constructed to bind Exo derived from human umbilical cord mesenchymal stem cells to treat myocardial injuries after myocardial infarction-ischemia/reperfusion (MI-I/R). To this end, a hyperbranched epoxy macromer (EHBPE) grafted by an aniline tetramer (AT) was synthesized to cross-link thiolated hyaluronic acid (HA-SH) and thiolated Exo anchoring a CP05 peptide via an epoxy/thiol "click" reaction. The resulting Gel@Exo composite system possesses multiple features, such as controllable gelation kinetics, shear-thinning injectability, conductivity matching the native myocardium, soft and dynamic stability adapting to heartbeats, and excellent cytocompatibility. After being injected into injured hearts of rats, the hydrogel effectively prolongs the retention of Exo in the ischemic myocardium. The cardiac functions have been considerably improved by Gel@Exo administration, as indicated by the enhancing ejection fraction and fractional shortening, and reducing fibrosis area. Immunofluorescence staining and reverse transcription-polymerase chain reaction (RT-PCR) results demonstrate that the expression of cardiac-related proteins (Cx43, Ki67, CD31, and α-SMA) and genes (VEGF-A, VEGF-B, vWF, TGF-ß1, MMP-9, and Serca2a) are remarkably upregulated. The conductive Gel@Exo system can significantly improve cell-to-cell interactions, promote cell proliferation and angiogenesis, and result in a prominent therapeutic effect on MI-I/R, providing a promising therapeutic method for injured myocardial tissues.

29Si Isotope-Enriched Silicon Nanoparticles for an Efficient Hyperpolarized Magnetic Resonance Imaging Probe.

Silicon particles have garnered attention as promising biomedical probes for hyperpolarized 29Si magnetic resonance imaging and spectroscopy. However, due to the limited levels of hyperpolarization for nanosized silicon particles, microscale silicon particles have primarily been the focus of dynamic nuclear polarization (DNP) applications, including in vivo magnetic resonance imaging (MRI). To address these current challenges, we developed a facile synthetic method for partially 29Si-enriched porous silicon nanoparticles (NPs) (160 nm) and examined their usability in hyperpolarized 29Si MRI agents with enhanced signals in spectroscopy and imaging. Hyperpolarization characteristics, such as the build-up constant, the depolarization time (T1), and the overall enhancement of the 29Si-enriched silicon NPs (10 and 15%), were thoroughly investigated and compared with those of a naturally abundant NP (4.7%). During optimal DNP conditions, the 15% enriched silicon NPs showed more than 16-fold higher enhancements─far beyond the enrichment ratio─than the naturally abundant sample, further improving the signal-to-noise ratio in in vivo 29Si MRI. The 29Si-enriched porous silicon NPs used in this work are potentially capable to serve as drug-delivery vehicles in addition to hyperpolarized 29Si in vivo, further enabling their potential future applicability as a theragnostic platform.

Injectable non-leaching tissue-mimetic bottlebrush elastomers as an advanced platform for reconstructive surgery.

Current materials used in biomedical devices do not match tissue's mechanical properties and leach various chemicals into the body. These deficiencies pose significant health risks that are further exacerbated by invasive implantation procedures. Herein, we leverage the brush-like polymer architecture to design and administer minimally invasive injectable elastomers that cure in vivo into leachable-free implants with mechanical properties matching the surrounding tissue. This strategy allows tuning curing time from minutes to hours, which empowers a broad range of biomedical applications from rapid wound sealing to time-intensive reconstructive surgery. These injectable elastomers support in vitro cell proliferation, while also demonstrating in vivo implant integrity with a mild inflammatory response and minimal fibrotic encapsulation.

miR-451 protects against ischemic stroke by targeting Phd3.

Ischemic stroke still remains a therapeutic challenge due to its complex pathogenesis and implications. By screening biomarkers in the peripheral blood of ischemic stroke patients, miR-451 was identified as a differentially expressed miRNA along the disease course of ischemic stroke. To investigate the role of miR-451, middle cerebral artery occlusion (MCAO) was performed as an ischemic stroke model in mice. Intracerebroventricular administration of miR-451 mimic in the MCAO mice significantly decreased infarct size, while miR-451 inhibitor significantly increased infarct size. To understand the molecular mechanism of the protective effect of miR-451, Phd3 (also Egln3) was validated as a new miR-451 target. Either fewer or more Phd3-positive cells were observed in brain sections from mice receiving miR-451 mimic or inhibitor, respectively. In addition, the levels of p53 (a known Phd3 target) were significantly downregulated when the levels of Phd3 were reduced, suggesting its participation in reducing apoptosis after the miR-451 administration. Indeed, reduced apoptosis upon miR-451 mimic administration was detected by TUNEL staining. In conclusion, this study demonstrated a new protective role of miR-451 in cerebral ischemia and identified Phd3 as a novel miR-451 target, linking the mechanism to the involvement of p53 in the regulation of apoptosis during the pathogenesis of ischemic stroke.

Modulation of the mucosal immune response of red tilapia (Oreochromis sp.) against columnaris disease using a biomimetic-mucoadhesive nanovaccine.

Columnaris, a highly contagious bacterial disease caused by Flavobacterium columnare, is recognized as one of the most important infectious diseases in farmed tilapia, especially during the fry and fingerling stages of production. The disease is associated with characteristic lesions in the mucosa of affected fish, particularly their skin and gills. Vaccines delivered via the mucosa are therefore of great interest to scientists developing vaccines for this disease. In the present study, we characterized field isolates of F. columnare obtained from clinical columnaris outbreaks in red tilapia to select an isolate to use as a candidate for our vaccine study. This included characterizing its colony morphology, genotype and virulence status. The isolate was incorporated into a mucoadhesive polymer chitosan-complexed nanovaccine (CS-NE), the efficacy of which was determined by experimentally infecting red tilapia that had been vaccinated with the nanoparticles by immersion. The experimental infection was performed 30-days post-vaccination (dpv), which resulted in 89% of the unvaccinated control fish dying, while the relative percentage survival (RPS) of the CS-NE vaccinated group was 78%. Histology of the mucosal associated lymphoid tissue (MALT) showed a significantly higher presence of leucocytes and a greater antigen uptake by the mucosal epithelium in CS-NE vaccinated fish compared to control fish and whole cell vaccinated fish, respectively, and there was statistically significant up-regulation of IgT, IgM, TNF α, IL1-ß and MHC-1 genes in the gill of the CS-NE vaccinated group. Overall, the results of our study confirmed that the CS-NE particles achieved better adsorption onto the mucosal surfaces of the fish, elicited great vaccine efficacy and modulated the MALT immune response better than the conventional whole cell-killed vaccine, demonstrating the feasibility of the mucoadhesive nano-immersion vaccine as an effective delivery system for the induction of a mucosal immune response against columnaris disease in tilapia.

Nanozymes go oral: nanocatalytic medicine facilitates dental health.

Nanozymes are multi-functional nanomaterials with enzyme-like activity, which rapidly won a place in biomedicine due to their number of nanocatalytic materials types and applications. Yan and Gao first discovered horseradish peroxidase-like activity in ferromagnetic nanoparticles in 2007. With the joint efforts of many scientists, a new concept-nanocatalytic medicine-is emerging. Nanozymes overcome the inherent disadvantages of natural enzymes, such as poor environmental stability, high production costs, difficult storage and so on. Their progress in dentistry is following the advancement of materials science. The oral research and application of nanozymes is becoming a new branch of nanocatalytic medicine. In order to highlight the great contribution of nanozymes facilitating dental health, we first review the overall research progress of multi-functional nanozymes in oral related diseases, including treating dental caries, dental pulp diseases, oral ulcers and peri-implantitis; the monitoring of oral cancer, oral bacteria and ions; and the regeneration of soft and hard tissue. Additionally, we also propose the challenges remaining for nanozymes in terms of their research and application, and mention future concerns. We believe that the new catalytic nanomaterials will play important roles in dentistry in the future.

Novel biomimetic nanostructured lipid carriers for cancer therapy: preparation, characterization, and in vitro/in vivo evaluation.

Nanostructured lipid carriers (NLC) have become a research hotspot, wherein cancer-targeting effects are enhanced and side effects of chemotherapy are overcome. Usually, accelerated blood clearance (ABC) occurs after repeated injections, without changing the immunologic profile, despite PEGylation which prolongs the circulation function. To overcome these problems, we designed a red blood cell-membrane-coated NLC (RBCm-NLC), which was round-like, with a particle size of 60.33 ± 3.04 nm and a core-shell structure. Its stability was good, the drug paclitaxel (PTX) release from RBCm-PTX-NLC was less than 30% at pH7.4 and pH6.5, and the integrity of RBC membrane surface protein was maintained before and after preparation. Additionally, in vitro assays showed that, with the RBCm coating, the cellular uptake of the NLC by cancer cells was significantly enhanced. RBCm-NLC can avoid recognition by macrophage cells and prolong circulation time in vivo. In S180 tumor-bearing mice, the DiR-labeled RBCm-NLC group showed a stronger fluorescence signal and longer retention in tumor tissues, indicating a prompt tumor-targeting effect and extended blood circulation. Importantly, RBCm-PTX-NLC enhanced the antitumor effect and extended the survival period significantly in vivo. In summary, biomimetic NLC offered a novel strategy for drug delivery in cancer therapy.

Mimetics of extra virgin olive oil phenols with anti-cancer stem cell activity.

The extra virgin olive oil (EVOO) dihydroxy-phenol oleacein is a natural inhibitor of multiple metabolic and epigenetic enzymes capable of suppressing the functional traits of cancer stem cells (CSC). Here, we used a natural product-inspired drug discovery approach to identify new compounds that phenotypically mimic the anti-CSC activity of oleacein. We coupled 3D quantitative structure-activity relationship-based virtual profiling with phenotypic analysis using 3D tumorsphere formation as a gold standard for assessing the presence of CSC. Among the top 20 computationally-predicted oleacein mimetics, four fulfilled the phenotypic endpoint of specifically suppressing the tumorsphere-initiating capacity of CSC, in the absence of significant cytotoxicity against differentiated cancer cells growing in 2D cultures in the same low micromolar concentration range. Of these, 3,4-dihydrophenetyl butyrate -a lipophilic ester conjugate of the hydroxytyrosol moiety of oleacein- and (E)-N-allyl-2-((5-nitrofuran-2-yl)methylene)hydrazinecarbothioamide) -an inhibitor of Trypanosoma cruzi triosephosphate isomerase- were also highly effective at significantly reducing the proportion of aldehyde dehydrogenase (ALDH)-positive CSC-like proliferating cells. Preservation of the mTOR/DNMT binding mode of oleacein was dispensable for suppression of the ALDH+-CSC functional phenotype in hydroxytyrosol-unrelated mimetics. The anti-CSC chemistry of complex EVOO phenols such as oleacein can be phenocopied through the use of mimetics capturing its physico-chemical properties.

Controllable gelation of artificial extracellular matrix for altering mass transport and improving cancer therapies.

Global alterations in the metabolic network provide substances and energy to support tumor progression. To fuel these metabolic processes, extracellular matrix (ECM) plays a dominant role in supporting the mass transport and providing essential nutrients. Here, we report a fibrinogen and thrombin based coagulation system to construct an artificial ECM (aECM) for selectively cutting-off the tumor metabolic flux. Once a micro-wound is induced, a cascaded gelation of aECM can be triggered to besiege the tumor. Studies on cell behaviors and metabolomics reveal that aECM cuts off the mass transport and leads to a tumor specific starvation to inhibit tumor growth. In orthotopic and spontaneous murine tumor models, this physical barrier also hinders cancer cells from distant metastasis. The in vivo gelation provides an efficient approach to selectively alter the tumor mass transport. This strategy results in a 77% suppression of tumor growth. Most importantly, the gelation of aECM can be induced by clinical operations such as ultrasonic treatment, surgery or radiotherapy, implying this strategy is potential to be translated into a clinical combination regimen.

A Systems Biology Workflow for Drug and Vaccine Repurposing: Identifying Small-Molecule BCG Mimics to Reduce or Prevent COVID-19 Mortality.

PURPOSE: Coronavirus disease 2019 (COVID-19) is expected to continue to cause worldwide fatalities until the World population develops 'herd immunity', or until a vaccine is developed and used as a prevention. Meanwhile, there is an urgent need to identify alternative means of antiviral defense. Bacillus Calmette-Guérin (BCG) vaccine that has been recognized for its off-target beneficial effects on the immune system can be exploited to boast immunity and protect from emerging novel viruses. METHODS: We developed and employed a systems biology workflow capable of identifying small-molecule antiviral drugs and vaccines that can boast immunity and affect a wide variety of viral disease pathways to protect from the fatal consequences of emerging viruses. RESULTS: Our analysis demonstrates that BCG vaccine affects the production and maturation of naïve T cells resulting in enhanced, long-lasting trained innate immune responses that can provide protection against novel viruses. We have identified small-molecule BCG mimics, including antiviral drugs such as raltegravir and lopinavir as high confidence hits. Strikingly, our top hits emetine and lopinavir were independently validated by recent experimental findings that these compounds inhibit the growth of SARS-CoV-2 in vitro. CONCLUSIONS: Our results provide systems biology support for using BCG and small-molecule BCG mimics as putative vaccine and drug candidates against emergent viruses including SARS-CoV-2.

Hemoglobin-mediated biomimetic synthesis of paramagnetic O2-evolving theranostic nanoprobes for MR imaging-guided enhanced photodynamic therapy of tumor.

The hypoxic microenvironment in solid tumors severely limits the efficacy of photodynamic therapy (PDT). Therefore, the development of nanocarriers co-loaded with photosensitizers and oxygen, together with imaging guidance ability, is of great significance in cancer therapy. However, previously reported synthetic methods for these multi-functional probes are complicated, and the raw materials used are toxic. Methods: Herein, the human endogenous protein, hemoglobin (Hb), was used for the simultaneous biomimetic synthesis of Gd-based nanostructures and co-loading of Chlorine e6 (Ce6) and oxygen for alleviating the hypoxic environment of tumors and accomplishing magnetic resonance imaging (MRI)-guided enhanced PDT. The Gd@HbCe6-PEG nanoprobes were synthesized via a green and protein biomimetic approach. The physicochemical properties, including relaxivity, oxygen-carrying/release capability, and PDT efficacy of Gd@HbCe6-PEG, were measured in vitro and in vivo on tumor-bearing mice after intravenous injection. Morphologic and functional MRI were carried out to evaluate the efficacy of PDT. Results: The results demonstrated the successful synthesis of compact Gd@HbCe6-PEG nanostructures with desired multi-functionalities. Following treatment with the nanoparticles, the embedded MR moiety was effective in lighting tumor lesions and guiding therapy. The oxygen-carrying capability of Hb after biomimetic synthesis was confirmed by spectroscopic analysis and oxygen detector in vitro. Further, tumor oxygenation for alleviating tumor hypoxia in vivo after intravenous injection of Gd@HbCe6-PEG was verified by photoacoustic imaging and immunofluorescence staining. The potent treatment efficacy of PDT on early-stage was observed by the morphologic and functional MR imaging. Importantly, rapid renal clearance of the particles was observed after treatment. Conclusion: In this study, by using a human endogenous protein, we demonstrated the biomimetic synthesis of multi-functional nanoprobes for simultaneous tumor oxygenation and imaging-guided enhanced PDT. The therapeutic efficacy could be quantitatively confirmed at 6 h post PDT with diffusion-weighted imaging (DWI).

Bioinspired biliverdin/silk fibroin hydrogel for antiglioma photothermal therapy and wound healing.

Rationale: Photothermal therapy employs the photoabsorbers to generate heat under the near-infrared (NIR) irradiation for thermal tumor ablation. However, NIR irradiation might damage the adjacent tissue due to the leakage of the photoabsorbers and the residual materials after treatment might hinder the local healing process. A bifunctional hydrogel that holds both photothermal property and potent pro-healing ability provides a viable option to resolve this issue. Methods: In this study, we developed a bioinspired green hydrogel (BVSF) with the integration of bioproduct biliverdin into natural derived silk fibroin matrix for antiglioma photothermal therapy and wound healing. Results: The BVSF hydrogel possessed excellent and controllable photothermal activity under NIR irradiation and resulted in effective tumor ablation both in vitro and in vivo. Additionally, the BVSF hydrogel exerted anti-inflammatory effects both in vitro and in vivo, and stimulated angiogenesis and wound healing in a full-thickness defect rat model. Conclusion: Overall, this proof-of-concept study was aimed to determine the feasibility and reliability of using an all-natural green formulation for photothermal therapy and post-treatment care.

Molecularly Imprinted Polymers: Antibody Mimics for Bioimaging and Therapy.

Molecularly imprinted polymers (MIPs) are tailor-made chemical receptors that recognize and bind target molecules with a high affinity and selectivity. MIPs came into the spotlight in 1993 when they were dubbed "antibody mimics," and ever since, they have been widely studied for the extraction or trapping of chemical pollutants, in immunoassays, and for the design of sensors. Owing to novel synthesis strategies resulting in more biocompatible MIPs in the form of soluble nanogels, these synthetic antibodies have found favor in the biomedical domain since 2010, when for the first time, they were shown to capture and eliminate a toxin in live mice. This review, covering the years 2015-2020, will first describe the rationale behind these antibody mimics, and the different synthesis methods that have been employed for the preparation of MIPs destined for in vitro and in vivo targeting and bioimaging of cancer biomarkers, an emerging and fast-growing area of MIP applications. MIPs have been synthesized for targeting and visualizing glycans and protein-based cell receptors overexpressed in certain diseases, which are well-known biomarkers for example for tumors. When loaded with drugs, the MIPs could locally kill the tumor cells, making them efficient therapeutic agents. We will end the review by reporting how MIPs themselves can act as therapeutics by inhibiting cancer growth. These works mark a new opening in the use of MIPs for antibody therapy and even immunotherapy, as materials of the future in nanomedicine.

Biomimetic theranostic strategy for anti-metastasis therapy of breast cancer via the macrophage membrane camouflaged superparticles.

The rational design of theranostic systems are critical for addressing challenging issues associated with cancers. Toward this objective, the multifunctional biomimetic superparticle, termed as DOX-QDs-Lip@M, which can specifically deliver drug to tumor and synergistically monitor their therapeutic effects, was fabricated. Initially, anticancer drug doxorubicin hydrochloride (DOX) and imaging agent quaternary quantum dots (QDs) were loaded into the hydrophilic core region and hydrophobic chamber of liposome by self-assembly method, respectively. The integrated nanostructure can greatly increase the fluorescence intensity of signal unit and tremendously improve the diagnostic sensitivity. Subsequently, the biomimetic DOX-QDs-Lip@M was constructed by fusing and coating the isolated macrophage membranes on the surface of liposome, which can consequently extend the circulation of the whole blood and effectively target the tumor sites. Moreover, the naturally formed biofilm can stabilize the artificial liposome structure, which can prevent the leakage of the loaded materials in the liposome. These integrated properties endow the biomimetic DOX-QDs-Lip@M with improved tumor imaging and anti-metastasis treatment in living systems.

Biomimetic hydrogels with spatial- and temporal-controlled chemical cues for tissue engineering.

Biomimetic hydrogels have emerged as the most useful tissue engineering scaffold materials. Their versatile chemistry can recapitulate multiple physical and chemical features to integrate cells, scaffolds, and signaling molecules for tissue regeneration. Due to their highly hydrophilic nature hydrogels can recreate nutrient-rich aqueous environments for cells. Soluble regulatory molecules can be incorporated to guide cell proliferation and differentiation. Importantly, the controlled dynamic parameters and spatial distribution of chemical cues in hydrogel scaffolds are critical for cell-cell communication, cell-scaffold interaction, and morphogenesis. Herein, we review biomimetic hydrogels that provide cells with spatiotemporally controlled chemical cues as tissue engineering scaffolds. Specifically, hydrogels with temporally controlled growth factor-release abilities, spatially controlled conjugated bioactive molecules/motifs, and targeting delivery and reload properties for tissue engineering applications are discussed in detail. Examples of hydrogels that possess clinically favorable properties, such as injectability, self-healing ability, stimulus-responsiveness, and pro-remodeling features, are also covered.