Advances in Nano-Functional Materials in Targeted Thrombolytic Drug Delivery.

Thrombotic disease has been listed as the third most fatal vascular disease in the world. After decades of development, clinical thrombolytic drugs still cannot avoid the occurrence of adverse reactions such as bleeding. A number of studies have shown that the application of various nano-functional materials in thrombus-targeted drug delivery, combined with external stimuli, such as magnetic, near-infrared light, ultrasound, etc., enrich the drugs in the thrombus site and use the properties of nano-functional materials for collaborative thrombolysis, which can effectively reduce adverse reactions such as bleeding and improve thrombolysis efficiency. In this paper, the research progress of organic nanomaterials, inorganic nanomaterials, and biomimetic nanomaterials for drug delivery is briefly reviewed.

Biomimetic retractable DNA nanocarrier with sensitive responsivity for efficient drug delivery and enhanced photothermal therapy.

BACKGROUND: The coalition of DNA nanotechnology with diversiform inorganic nanoparticles offers powerful tools for the design and construction of stimuli-responsive drug delivery systems with spatiotemporal controllability, but it remains challenging to achieve high-density oligonucleotides modification close to inorganic nanocores for their sensitive responsivity to optical or thermal signals. RESULTS: Inspired by Actinia with retractable tentacles, here we design an artificial nano-Actinia consisted of collapsible DNA architectures attached on gold nanoparticle (AuNP) for efficient drug delivery and enhanced photothermal therapy. The collapsible spheroidal architectures are formed by the hybridization of long DNA strand produced in situ through rolling circle amplification with bundling DNA strands, and contain numerous double-helical segments for the intercalative binding of quercetin as the anti-cancer drug. Under 800-nm light irradiation, the photothermal conversion of AuNPs induces intensive localized heating, which unwinds the double helixes and leads to the disassembly of DNA nanospheres on the surface of AuNPs. The consequently released quercetin can inhibit the expression of heat shock protein 27 and decrease the thermal resistance of tumor cells, thus enhancing photothermal therapy efficacy. CONCLUSIONS: By combining the deformable DNA nanostructures with gold nanocores, this Actinia-mimetic nanocarrier presents a promising tool for the development of DNA-AuNPs complex and opens a new horizon for the stimuli-responsive drug delivery.

Erythrocyte membrane with CLIPPKF as biomimetic nanodecoy traps merozoites and attaches to infected red blood cells to prevent Plasmodium infection.

BACKGROUND: Malaria remains a serious threat to global public health. With poor efficacies of vaccines and the emergence of drug resistance, novel strategies to control malaria are urgently needed. RESULTS: We developed erythrocyte membrane-camouflaged nanoparticles loaded with artemether based on the growth characteristics of Plasmodium. The nanoparticles could capture the merozoites to inhibit them from repeatedly infecting normal erythrocytes, owing to the interactions between merozoites and heparin-like molecules on the erythrocyte membrane. Modification with a phosphatidylserine-targeting peptide (CLIPPKF) improved the drug accumulation in infected red blood cells (iRBCs) from the externalized phosphatidylserine induced by Plasmodium infection. In Plasmodium berghei ANKA strain (pbANKA)-infected C57BL/6 mice, the nanoparticles significantly attenuated Plasmodium-induced inflammation, apoptosis, and anemia. We observed reduced weight variation and prolonged survival time in pbANKA-challenged mice, and the nanoparticles showed good biocompatibility and negligible cytotoxicity. CONCLUSION: Erythrocyte membrane-camouflaged nanoparticles loaded with artemether were shown to provide safe and effective protection against Plasmodium infection.

Solid-phase synthesis of three-armed star-shaped peptoids and their hierarchical self-assembly.

Due to the branched structure feature and unique properties, a variety of star-shaped polymers have been designed and synthesized. Despite those advances, solid-phase synthesis of star-shaped sequence-defined synthetic polymers that exhibit hierarchical self-assembly remains a significant challenge. Hence, we present an effective strategy for the solid-phase synthesis of three-armed star-shaped peptoids, in which ethylenediamine was used as the centric star pivot. Based on the sequence of monomer addition, a series of AA'A''-type and ABB'-type peptoids were synthesized and characterized by UPLC-MS (ultrahigh performance liquid chromatography-mass spectrometry). By taking advantage of the easy-synthesis and large side-chain diversity, we synthesized star-shaped peptoids with tunable functions. We further demonstrated the aqueous self-assembly of some representative peptoids into biomimetic nanomaterials with well-defined hierarchical structures, such as nanofibers and nanotubes. These results indicate that star-shaped peptoids offer the potential in self-assembly of biomimetic nanomaterials with tunable chemistries and functions.

Carbon dots on V2O5 nanowires are a viable peroxidase mimic for colorimetric determination of hydrogen peroxide and glucose.

A nanocomposite was hydrothermally prepared from C-dots and V2O5 nanowires, and characterized by TEM, FTIR and XRD. Due to the synergistic effects between C-dots and V2O5 nanowires, the nanocomposite is found to possess peroxidase-mimicking activity. This finding was exploited to design colorimetric methods for determination of H2O2 and glucose (via glucose oxidase) by using of 3,3',5,5'-tetramethylbenzidine (TMB) as the chromogenic substrate. The C-dot/V2O5 nanocomposite catalyzes hydrogen peroxide to oxidize TMB and the resultant product, i.e., TMB* produces a blue color in the solution. Also for glucose determination, at first glucose reacts with dissolved oxygen in the presence of glucose oxidase and generates H2O2. Then, produced H2O2 was monitored by the C-dot/V2O5 nanozyme in the presence of TMB. Intensity of the blue color in the solution at wavelength of 650 nm is an indication of H2O2 or glucose concentration. The response to H2O2 is linear in the 0.5-520 µM concentration ranges, and that for glucose from 0.7 µM to 300 µM. Graphical abstract Schematic presentation of peroxidase mimicking activity of C-dot/V2O5 nanocomposite and its application as sensitive colorimetric H2O2/glucose assay by using of 3,3',5,5'-tetramethylbenzidine (TMB) as chromogenic substrate to induce a typical blue color reaction.

Nano-Engineered Biomimetic Optical Sensors for Glucose Monitoring in Diabetes.

Diabetes is a rapidly growing disease that can be monitored at an individual level by controlling the blood glucose level, hence minimizing the negative impact of the disease. Significant research efforts have been focused on the design of novel and improved technologies to overcome the limitations of existing glucose analysis methods. In this context, nanotechnology has enabled the diagnosis at the single cell and molecular level with the possibility of incorporation in advanced molecular diagnostic biochips. Recent years have witnessed the exploration and synthesis of various types of nanomaterials with enzyme-like properties, with their subsequent integration into the design of biomimetic optical sensors for glucose monitoring. This review paper will provide insights on the type, nature and synthesis of different biomimetic nanomaterials. Moreover, recent developments in the integration of these nanomaterials for optical glucose biosensing will be highlighted, with a final discussion on the challenges that must be addressed for successful implementation of these nano-devices in the clinical applications is presented.

Biomimetic Chiral Nanomaterials with Selective Catalysis Activity.

Chiral nanomaterials with unique chiral configurations and biocompatible ligands have been booming over the past decade for their interesting chiroptical effect, unique catalytical activity, and related bioapplications. The catalytic activity and selectivity of chiral nanomaterials have emerged as important topics, that can be potentially controlled and optimized by the rational biochemical design of nanomaterials. In this review, chiral nanomaterials synthesis, composition, and catalytic performances of different biohybrid chiral nanomaterials are discussed. The construction of chiral nanomaterials with multiscale chiral geometries along with the underlying principles for enhancing chiroptical responses are highlighted. Various biochemical approaches to regulate the selectivity and catalytic activity of chiral nanomaterials for biocatalysis are also summarized. Furthermore, attention is paid to specific chiral ligands, materials compositions, structure characteristics, and so on for introducing selective catalytic activities of representative chiral nanomaterials, with emphasis on substrates including small molecules, biological macromolecule, and in-site catalysis in living systems. Promising progress has also been emphasized in chiral nanomaterials featuring structural versatility and improved chiral responses that gave rise to unprecedented chances to utilize light for biocatalytic applications. In summary, the challenges, future trends, and prospects associated with chiral nanomaterials for catalysis are comprehensively proposed.

Biomimetic nanomaterials in myocardial infarction treatment: Harnessing bionic strategies for advanced therapeutics.

Myocardial infarction (MI) and its associated poor prognosis pose significant risks to human health. Nanomaterials hold great potential for the treatment of MI due to their targeted and controlled release properties, particularly biomimetic nanomaterials. The utilization of biomimetic strategies based on extracellular vesicles (EVs) and cell membranes will serve as the guiding principle for the development of nanomaterial therapy in the future. In this review, we present an overview of research progress on various exosomes derived from mesenchymal stem cells, cardiomyocytes, or induced pluripotent stem cells in the context of myocardial infarction (MI) therapy. These exosomes, utilized as cell-free therapies, have demonstrated the ability to enhance the efficacy of reducing the size of the infarcted area and preventing ischaemic reperfusion through mechanisms such as oxidative stress reduction, polarization modulation, fibrosis inhibition, and angiogenesis promotion. Moreover, EVs can exert cardioprotective effects by encapsulating therapeutic agents and can be engineered to specifically target the infarcted myocardium. Furthermore, we discuss the use of cell membranes derived from erythrocytes, stem cells, immune cells and platelets to encapsulate nanomaterials. This approach allows the nanomaterials to camouflage themselves as endogenous substances targeting the region affected by MI, thereby minimizing toxicity and improving biocompatibility. In conclusion, biomimetic nano-delivery systems hold promise as a potentially beneficial technology for MI treatment. This review serves as a valuable reference for the application of biomimetic nanomaterials in MI therapy and aims to expedite the translation of NPs-based MI therapeutic strategies into practical clinical applications.

Research Progress on Biomimetic Nanomaterials for Electrochemical Glucose Sensors.

Diabetes has become a chronic disease that necessitates timely and accurate detection. Among various detection methods, electrochemical glucose sensors have attracted much attention because of low cost, real-time detection, and simple and easy operation. Nonenzymatic biomimetic nanomaterials are the vital part in electrochemical glucose sensors. This review article summarizes the methods to enhance the glucose sensing performance of noble metal, transition metal oxides, and carbon-based materials and introduces biomimetic nanomaterials used in noninvasive glucose detection in sweat, tear, urine, and saliva. Based on these, this review provides the foundation for noninvasive determination of trace glucose for diabetic patients in the future.

Dual-Targeting Biomimetic Nanomaterials for Photo-/Chemo-/Antiangiogenic Synergistic Therapy.

Avoiding the low specificity of phototheranostic reagents at the tumor site is a major challenge in cancer phototherapy. Meanwhile, angiogenesis in the tumor is not only the premise of tumor occurrence but also the basis of tumor growth, invasion, and metastasis, making it an ideal strategy for tumor therapy. Herein, biomimetic cancer cell membrane-coated nanodrugs (mBPP NPs) have been prepared by integrating (i) homotypic cancer cell membranes for evading immune cell phagocytosis to increase drug accumulation, (ii) protocatechuic acid for tumor vascular targeting along with chemotherapy effect, and (iii) near-infrared phototherapeutic agent diketopyrrolopyrrole derivative for photodynamic/photothermal synergetic therapy. The mBPP NPs exhibit high biocompatibility, superb phototoxicity, excellent antiangiogenic ability, and double-trigging cancer cell apoptosis in vitro. More significantly, mBPP NPs could specifically bind to tumor cells and vasculature after intravenous injection, inducing fluorescence and photothermal imaging-guided tumor ablation without recurrence and side effects in vivo. The biomimetic mBPP NPs could cause drug accumulation at the tumor site, inhibit tumor neovascularization, and improve phototherapy efficiency, providing a novel avenue for cancer treatment.

Application of Cell Membrane-Coated Nanomaterials for Tumor Treatment.

Tumors are a major cause of human mortality worldwide, and the rapid development of nanomaterials (NMs) for tumor therapy and drug delivery has provided new treatment methods. However, NMs' high immunogenicity, short circulation time, and low specificity limit their application in tumor therapy. In recent years, bionanomaterials using cell membranes have emerged to overcome the shortcomings of monomeric NMs. Cell membrane-encapsulated NMs extracted from multiple cells not only retain the physicochemical properties of NMs but also inherit the biological functions of the source cells, aiding in drug delivery. The combination of the cell membrane and drug-loading NMs offers an efficient and targeted drug delivery system tailored to the tumor microenvironment. The research and application of this method have been widely carried out in the academic field of tumor diagnosis and treatment. This review presents the recent research progress of cell membrane-coated NMs as drug carriers in tumor therapy, including cell membrane extraction methods, encapsulation strategies, and the applications of cell membrane-encapsulated NMs in tumor therapy. We believe that biomimetic nanomaterials will be a promising and novel anticancer strategy in the future, and their wide application will certainly bring vitality to the field of tumor diagnosis and treatment. The combination of membrane and drug-loading nanomaterials embodies a highly efficient and target drug delivery system tailored to the tumor microenvironment, which broadens a new path of drug delivery for future cancer treatment. Meanwhile, it is also a perfect combination and application of biomedical nanomaterials, which is of great significance.

Advanced bioactive nanomaterials for diagnosis and treatment of major chronic diseases.

With the rapid innovation of nanoscience and technology, nanomaterials have also been deeply applied in the medical and health industry and become one of the innovative methods to treat many diseases. In recent years, bioactive nanomaterials have attracted extensive attention and have made some progress in the treatment of some major chronic diseases, such as nervous system diseases and various malignant tumors. Bioactive nanomaterials depend on their physical and chemical properties (crystal structure, surface charge, surface functional groups, morphology, and size, etc.) and direct produce biological activity and play to the role of the treatment of diseases, compared with the traditional nanometer pharmaceutical preparations, biological active nano materials don't exert effects through drug release, way more directly, also is expected to be more effective for the treatment of diseases. However, further studies are needed in the evaluation of biological effects, fate in vivo, structure-activity relationship and clinical transformation of bionanomaterials. Based on the latest research reports, this paper reviews the application of bioactive nanomaterials in the diagnosis and treatment of major chronic diseases and analyzes the technical challenges and key scientific issues faced by bioactive nanomaterials in the diagnosis and treatment of diseases, to provide suggestions for the future development of this field.

Spanning Network Gels from Nanoparticles and Graph Theoretical Analysis of Their Structure and Properties.

Gels self-assembled from colloidal nanoparticles (NPs) translate the size-dependent properties of nanostructures to materials with macroscale volumes. Large spanning networks of NP chains provide high interconnectivity within the material necessary for a wide range of properties from conductivity to viscoelasticity. However, a great challenge for nanoscale engineering of such gels lies in being able to accurately and quantitatively describe their complex non-crystalline structure that combines order and disorder. The quantitative relationships between the mesoscale structural and material properties of nanostructured gels are currently unknown. Here, it is shown that lead telluride NPs spontaneously self-assemble into a spanning network hydrogel. By applying graph theory (GT), a method for quantifying the complex structure of the NP gels is established using a topological descriptor of average nodal connectivity that is found to correlate with the gel's mechanical and charge transport properties. GT descriptions make possible the design of non-crystalline porous materials from a variety of nanoscale components for photonics, catalysis, adsorption, and thermoelectrics.

An anti-inflammatory and neuroprotective biomimetic nanoplatform for repairing spinal cord injury.

Spinal cord regeneration after a spinal cord injury (SCI) remains a difficult challenge due to the complicated inflammatory microenvironment and neuronal damage at the injury sites. In this study, retinoic acid (RA) and curcumin (Cur) were co-loaded with bovine serum albumin (BSA) self-assembly to obtain RA@BSA@Cur nanoparticles (NPs) for SCI treatment. Cur, as an antioxidant drug, facilitated reactive oxygen species (ROS) scavenging, and decreased the amount of inflammatory factors secreted by macrophages, while RA could enhance neurite extensions and neural differentiation. The constructed RA@BSA@Cur NPs not only induced polarization of macrophages toward pro-regenerative phenotypes and markedly reduced the inflammatory response of macrophages or microglia, but also increased neurite length in PC12 cells and neuronal differentiation of bone marrow mesenchymal stem cells, improved the differentiation of neural stem cells (NSCs) into ß3-tubulin+ neurons, and reversed the pro-astrocyte differentiation effect of inflammatory cytokines on NSCs. In vivo experiments revealed that RA@BSA@Cur NPs regulated the phenotypic polarization of macrophages, inhibited the release of inflammatory mediators, promoted functional neuron regeneration and motor function, and further inhibited scar tissue formation. This study highlighted that the BSA-based biomimetic nanomaterials could be used as ROS scavengers and nerve regeneration promoters for treating SCI.

Ganglioside-Functionalized Nanoparticles for Chimeric Antigen Receptor T-Cell Activation at the Immunological Synapse.

Chimeric Antigen Receptor (CAR) T cell therapy has proven to be an effective strategy against hematological malignancies but persistence and activity against solid tumors must be further improved. One emerging strategy for enhancing efficacy is based on directing CAR T cells to antigen presenting cells (APCs). Activation of CAR T cells at the immunological synapse (IS) formed between APC and T cell is thought to promote strong, persistent antigen-specific T cell-mediated immune responses but requires integration of CAR ligands into the APC/T-cell interface. Here, we demonstrate that CAR ligand functionalized, lipid-coated, biodegradable polymer nanoparticles (NPs) that contain the ganglioside GM3 (GM3-NPs) bind to CD169 (Siglec-1)-expressing APCs and localize to the cell contact site between APCs and CAR T cells upon initiation of cell conjugates. The CD169+ APC/CAR T-cell interface is characterized by a strong optical colocalization of GM3-NPs and CARs, enrichment of F-actin, and recruitment of ZAP-70, indicative of integration of GM3-NPs into a functional IS. Ligands associated with GM3-NPs localized to the APC/T-cell contact site remain accessible to CARs and result in robust T-cell activation. Overall, this work identifies GM3-NPs as a potential antigen delivery platform for active targeting of CD169 expressing APCs and enhancement of CAR T-cell activation at the NP-containing IS.

Smart Nanocarriers for Targeted Cancer Therapy.

Cancer is considered one of the most threatening diseases worldwide. Although many therapeutic approaches have been developed and optimized for ameliorating patient's conditions and life expectancy, however, it frequently remains an incurable pathology. Notably, conventional treatments may reveal inefficient in the presence of metastasis development, multidrug resistance and inability to achieve targeted drug delivery. In the last decades, nanomedicine has gained a prominent role, due to many properties ascribable to nanomaterials. It is worth mentioning their small size, their ability to be loaded with small drugs and bioactive molecules and the possibility to be functionalized for tumor targeting. Natural vehicles have been exploited, such as exosomes, and designed, such as liposomes. Biomimetic nanomaterials have been engineered, by modification with biological membrane coating. Several nanoparticles have already entered clinical trials and some liposomal formulations have been approved for therapeutic applications. In this review, natural and synthetic nanocarriers functionalized for actively targeting cancer cells will be described, focusing on their advantages with respect to conventional treatments. Recent innovations related to biomimetic nanoparticles camouflaged with membranes isolated from different types of cells will be reported, together with their promising applications. Finally, a short overview on the latest advances in carrier-free nanomaterials will be provided.

Commitment of Autologous Human Multipotent Stem Cells on Biomimetic Poly-L-lactic Acid-Based Scaffolds Is Strongly Influenced by Structure and Concentration of Carbon Nanomaterial.

Nanocomposite scaffolds combining carbon nanomaterials (CNMs) with a biocompatible matrix are able to favor the neuronal differentiation and growth of a number of cell types, because they mimic neural-tissue nanotopography and/or conductivity. We performed comparative analysis of biomimetic scaffolds with poly-L-lactic acid (PLLA) matrix and three different p-methoxyphenyl functionalized carbon nanofillers, namely, carbon nanotubes (CNTs), carbon nanohorns (CNHs), and reduced graphene oxide (RGO), dispersed at varying concentrations. qRT-PCR analysis of the modulation of neuronal markers in human circulating multipotent cells cultured on nanocomposite scaffolds showed high variability in their expression patterns depending on the scaffolds' inhomogeneities. Local stimuli variation could result in a multi- to oligopotency shift and commitment towards multiple cell lineages, which was assessed by the qRT-PCR profiling of markers for neural, adipogenic, and myogenic cell lineages. Less conductive scaffolds, i.e., bare poly-L-lactic acid (PLLA)-, CNH-, and RGO-based nanocomposites, appeared to boost the expression of myogenic-lineage marker genes. Moreover, scaffolds are much more effective on early commitment than in subsequent differentiation. This work suggests that biomimetic PLLA carbon-nanomaterial (PLLA-CNM) scaffolds combined with multipotent autologous cells can represent a powerful tool in the regenerative medicine of multiple tissue types, opening the route to next analyses with specific and standardized scaffold features.

A lanthanide-peptide-derived bacterium-like nanotheranostic with high tumor-targeting, -imaging and -killing properties.

Nanostructures formed with bioactive peptides offer an exciting prospect in clinical oncology as a novel class of therapeutic agents for human cancers. Despite their therapeutic potential, however, peptide-based nanomedicines are often inefficacious in vivo due to low cargo-loading efficiency, poor tumor cell-targeting specificity and limited drug accumulation in tumor tissues. Here, we describe the design, via assembly of a p53-activating peptide termed PMI, functionalized PEG and fluorescent lanthanide oxyfluoride nanocrystals, of a novel nanotheranostic shaped in flexible rods. This lanthanide-peptide nanorod or LProd of bionic nature exhibited significantly enhanced tumor-targeting and -imaging properties compared to its spherical counterpart. Importantly, LProd potently inhibited tumor growth in a mouse model of human colon cancer through activating tumor suppressor protein p53 via MDM2/MDMX antagonism, while maintaining a highly favorable biosafety profile. Our data demonstrate that LProd as a multifunctional theranostic platform is ideally suited for tumor-specific peptide drug delivery with real-time disease tracking, thereby broadly impacting clinical development of antitumor peptides.

Biomimetic nanomaterials: Development of protein coated nanoceria as a potential antioxidative nano-agent for the effective scavenging of reactive oxygen species in vitro and in zebrafish model.

Reactive oxygen species (ROS) induced oxidative stress is one of the major factors responsible for initiation of several intracellular toxic events that leads to cell death. Antioxidant enzymes defence system of the body is responsible for maintaining the oxidative balance and cellular homeostasis. Several diseases are promoted by the excessive oxidative stress caused by the impaired antioxidant defence system that leads to oxidant/antioxidant imbalance in the body. In order to restore or precise the aberrant antioxidant system, a large number of catalytic nanoparticles has been screened so far. Exceptional antioxidative activity of nanoceria made it as a potential antioxidative nano-agent for the effective scavenging of toxic ROS. In this work albumin coated nanoceria (ANC) was synthesized and further characterised by various physicochemical techniques. The antioxidant and superoxide dismutase (SOD) assay confirm that the albumin coating do not alter the antioxidant potential of ANC. The biocompatibility and protective efficacy of ANC against oxidative stress was investigated both in vitro and in vivo in human lung epithelial (L-132) cells and zebrafish embryos, respectively. The inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy (TEM) and field emission scanning electron microscope (FE-SEM) analysis corroborates the uptake of ANC by the cells. Furthermore, the semi-quantitative gene expression studies confirmed that the ANC successfully defend the cells against oxidative stress by preserving the antioxidant system of the cells. Thus, the current work open up a new avenue for the development of improved antioxidant nano-drug therapies.