Construction of CpG Delivery Nanoplatforms by Functionalized MoS2 Nanosheets for Boosting Antitumor Immunity in Head and Neck Squamous Cell Carcinoma.

Despite the promising achievements of immune checkpoint blockade (ICB) therapy for tumor treatment, its therapeutic effect against solid tumors is limited due to the suppressed tumor immune microenvironment (TIME). Herein, a series of polyethyleneimine (Mw = 0.8k, PEI0.8k )-covered MoS2 nanosheets with different sizes and charge densities are synthesized, and the CpG, a toll-like receptor-9 agonist, is enveloped to construct nanoplatforms for the treatment of head and neck squamous cell carcinoma (HNSCC). It is proved that functionalized nanosheets with medium size display similar CpG loading capacity regardless of low or high PEI0.8k coverage owing to the flexibility and crimpability of 2D backbone. CpG-loaded nanosheets with medium size and low charge density (CpG@MM -PL ) could promote the maturation, antigen-presenting capacity, and proinflammatory cytokines generation of bone marrow-derived dendritic cells (DCs). Further analysis reveals that CpG@MM -PL effectively boosts the TIME of HNSCC in vivo including DC maturation and cytotoxic T lymphocyte infiltration. Most importantly, the combination of CpG@MM -PL and ICB agents anti-programmed death 1 hugely improves the tumor therapeutic effect, inspiring more attempts for cancer immunotherapy. In addition, this work uncovers a pivotal feature of the 2D sheet-like materials in nanomedicine development, which should be considered for the design of future nanosheet-based therapeutic nanoplatforms.

Positively Charged Nanoaggregates Based on Zwitterionic Pillar[5]arene that Combat Planktonic Bacteria and Disrupt Biofilms.

Bacterial biofilms are difficult to eradicate because they are less susceptible to antibiotics and more easily develop resistance. Therefore, there is an urgent need for new materials that can combat planktonic bacteria and disrupt established biofilms. To tackle this challenge, we design a multifunctional zwitterionic pillar[5]arene, which can self-assemble into weakly positively charged nanoaggregates that exhibit antibacterial activity against Gram-negative Escherichia coli (DH5α) and Gram-positive Staphylococcus aureus (SH1000) bacterial strains in solution. In addition, the zwitterionic pillar[5]arene can efficiently disrupt pre-existing Escherichia coli (DH5α) biofilms and kill the biofilm-enclosed bacteria without rapid generation of resistance.

Directed Graphene-Based Nanoplatforms for Hyperthermia: Overcoming Multiple Drug Resistance.

Multidrug resistance (MDR), which leads tumors resistance to traditional anticancer drugs, can cause the failure of chemotherapy treatments. Herein, we present a new way to overcome this problem using smart multifunctional graphene-based drug delivery systems which can target subcellular organelles and show synergistic hyperthermia and chemotherapy. Mitochondria-targeting ligands are conjugated onto the doxorubicin-loaded, polyglycerol-covered nanographene sheets to actively accumulate them inside the mitochondria after charge-mediated cellular internalization. Upon near-infrared (NIR) irradiation, adenosine triphosphate (ATP) synthesis and mitochondrial function were inhibited and doxorubicin released into the cellular interior. The hyperthermia-accelerated drug release led to a highly selective anticancer efficiency, confirmed by in vitro and in vivo experiments.

Bioreducible Peptide-Dendrimeric Nanogels with Abundant Expanded Voids for Efficient Drug Entrapment and Delivery.

Dendrimer-based nanoplatforms have exhibited wide prospects in the field of nanomedicine for drug delivery, without great success due to many predicaments of cytotoxicity, high cost, and low yield. In this work, we report a feasible strategy on dynamic cross-linkings of low-generation peptide dendrimers into bioreducible nanogels for efficient drug controlled release. With a facile fabrication, the disulfide cross-linking of biocompatible peptide dendrimers successfully possess well-defined and stable nanostructures with abundant expanded voids for efficient molecular encapsulation. More importantly, high reducing condition is capable of triggering the cleavage of disulfide bonds, the disintegration of peptide-dendrimeric nanogels, and stimuli-responsive release of guest molecules. The bioreducible nanogels improve antitumor drug internalization, contribute to endosomal escape, and realize intracellular drug controlled release. The doxorubicin-loaded nanogels afford high antitumor efficiency and reduce the side effects to BALB/c mice bearing 4T1 tumor. Therefore, dynamic cross-linkings of low-generation dendrimers into smart nanogels will be an alternative and promising strategy to resolve the dilemmas of current dendrimer-based nanocarriers as well as develop innovative nanoplatforms.

Multifunctional Cationic Hyperbranched Polyaminoglycosides that Target Multiple Mediators for Severe Abdominal Trauma Management.

Trauma and its associated complications, including dysregulated inflammatory responses, severe infection, and disseminated intravascular coagulation (DIC), continue to pose lethal threats worldwide. Following injury, cell-free nucleic acids (cfNAs), categorized as damage-associated molecular patterns (DAMPs), are released from dying or dead cells, triggering local and systemic inflammatory responses and coagulation abnormalities that worsen disease progression. Harnessing cfNA scavenging strategies with biomaterials has emerged as a promising approach for treating posttrauma systemic inflammation. In this study, the effectiveness of cationic hyperbranched polyaminoglycosides derived from tobramycin (HPT) and disulfide-included HPT (ss-HPT) in scavenging cfNAs to mitigate posttrauma inflammation and hypercoagulation is investigated. Both cationic polymers demonstrate the ability to suppress DAMP-induced toll-like receptor (TLR) activation, inflammatory cytokine secretion, and hypercoagulation by efficiently scavenging cfNAs. Additionally, HPT and ss-HPT exhibit potent antibacterial efficacy attributed to the presence of tobramycin in their chemical composition. Furthermore, HPT and ss-HPT exhibit favorable modulatory effects on inflammation and therapeutic outcomes in a cecal ligation puncture (CLP) mouse abdominal trauma model. Notably, in vivo studies reveal that ss-HPT displayed high accumulation and retention in injured organs of traumatized mice while maintaining a higher biodegradation rate in healthy mice, contrasting with findings for HPT. Thus, functionalized ss-HPT, a bioreducible polyaminoglycoside, holds promise as an effective option to enhance therapeutic outcomes for trauma patients by alleviating posttrauma inflammation and coagulation complications.

Functional 2D Nanoplatforms Alleviate Eosinophilic Chronic Rhinosinusitis by Modulating Eosinophil Extracellular Trap Formation.

The therapeutic outcomes of patients with eosinophilic chronic rhinosinusitis (ECRS) remain unsatisfactory, largely because the underlying mechanisms of eosinophilic inflammation are uncertain. Here, it is shown that the nasal secretions of ECRS patients have high eosinophil extracellular trap (EET) and cell-free DNA (cfDNA) levels. Moreover, the cfDNA induced EET formation by activating toll-like receptor 9 (TLR9) signaling. After demonstrating that DNase I reduced eosinophilic inflammation by modulating EET formation, linear polyglycerol-amine (LPGA)-coated TiS2 nanosheets (TLPGA) as functional 2D nanoplatforms with low cytotoxicity, mild protein adsorption, and increased degradation rate is developed. Due to the more flexible linear architecture, TLPGA exhibited higher cfDNA affinity than the TiS2 nanosheets coated with dendritic polyglycerol-amine (TDPGA). TLPGA reduced cfDNA levels in the nasal secretions of ECRS patients while suppressing cfDNA-induced TLR9 activation and EET formation in vitro. TLPGA displayed exceptional biocompatibility, preferential nasal localization, and potent inflammation modulation in mice with eosinophilic inflammation. These results highlight the pivotal feature of the linear molecular architecture and 2D sheet-like nanostructure in the development of anti-inflammation nanoplatforms, which can be exploited for ECRS treatment.

Inhibitory effects of black phosphorus nanosheets on tumor cell proliferation through downregulation of ADIPOQ and downstream signaling pathways.

Exposure to environmental pollutants, including nanomaterials, has a significant impact on tumor progression. The increased demand for black phosphorus nanosheets (BPNSs), driven by their exceptional properties, raises concerns about potential environmental contamination. Assessing their toxicity on tumor growth is essential. Herein, we employed a range of biological techniques, including cytotoxicity measurement, bioinformatics tools, proteomics, target gene overexpression, Western blot analysis, and apoptosis detection, to investigate the toxicity of BPNSs across A549, HepG-2, MCF-7, and Caco-2 cell lines. Our results demonstrated that BPNSs downregulated the expression of ADIPOQ and its associated downstream pathways, such as AMP-activated protein kinase (AMPK), nuclear factor erythroid 2-related factor 2 (Nrf2), and other unidentified pathways. These downregulated pathways ultimately led to mitochondria-dependent apoptosis. Notably, the specific downstream pathways involved varied depending on the type of tumors. These insightful findings not only confirm the consistent inhibitory effects of BPNSs across different tumor cells, but also elucidate the cytotoxicity mechanisms of BPNSs in different tumors, providing valuable information for their safe application and health risk assessment.

Tackling Severe Neutrophilic Inflammation in Airway Disorders with Functionalized Nanosheets.

Severe airway inflammatory disorders impose a significant societal burden, and the available treatments are unsatisfactory. High levels of neutrophil extracellular trap (NET) and cell-free DNA (cfDNA) were detected in the inflammatory microenvironment of these diseases, which are closely associated with persistent uncontrolled neutrophilic inflammation. Although DNase has proven to be effective in mitigating neutrophilic airway inflammation in mice by reducing cfDNA and NET levels, its clinical use is hindered by severe side effects. Here, we synthesized polyglycerol-amine (PGA) with a series of hydroxyl/amine ratios and covered them with black phosphorus (BP) nanosheets. The BP nanosheets functionalized with polyglycerol-50% amine (BP-PGA50) efficiently lowered cfDNA levels, suppressed toll-like receptor 9 (TLR9) activation and inhibited NET formation in vitro. Importantly, BP-PGA50 nanosheets demonstrated substantial accumulation in inflamed airway tissues, excellent biocompatibility, and potent inflammation modulation ability in model mice. The 2D sheet-like structure of BP-PGA50 was identified as a crucial factor for the therapeutic efficacy, and the hydroxyl/amine ratio was revealed as a significant parameter to regulate the protein resistance, cfDNA-binding efficacy, and cytotoxicity. This study shows the promise of the BP-PGA50 nanosheet for tackling uncontrolled airway inflammation, which is also significant for the treatment of other neutrophilic inflammatory diseases. In addition, our work also highlights the importance of proper surface functionalization, such as hydroxyl/amine ratio, in therapeutic nanoplatform construction for inflammation modulation.

Intranasal PAMAM-G3 scavenges cell-free DNA attenuating the allergic airway inflammation.

Allergic airway inflammation (AAI), including allergic rhinitis (AR) and allergic asthma, is driven by epithelial barrier dysfunction and type 2 inflammation. However, the underlying mechanism remains uncertain and available treatments are constrained. Consequently, we aim to explore the role of cell-free DNA (cfDNA) in AAI and assess the potential alleviating effects of cationic polymers (CPs) through cfDNA elimination. Levels of cfDNA were evaluated in AR patients, allergen-stimulated human bronchial epithelium (BEAS-2B cells) and primary human nasal epithelium from both AR and healthy control (HC), and AAI murine model. Polyamidoamine dendrimers-generation 3 (PAMAM-G3), a classic type of cationic polymers, were applied to investigate whether the clearance of cfDNA could ameliorate airway epithelial dysfunction and inhibit AAI. The levels of cfDNA in the plasma and nasal secretion from AR were higher than those from HC (P < 0.05). Additionally, cfDNA levels in the exhaled breath condensate (EBC) were positively correlated with Interleukin (IL)-5 levels in EBC (R = 0.4191, P = 0.0001). Plasma cfDNA levels negatively correlated with the duration of allergen immunotherapy treatment (R = -0.4297, P = 0.006). Allergen stimulated cfDNA secretion in vitro (P < 0.001) and in vivo (P < 0.0001), which could be effectively scavenged with PAMAM-G3. The application of PAMAM-G3 inhibited epithelial barrier dysfunction in vitro and attenuated the development of AAI in vivo. This study elucidates that cfDNA, a promising biomarker for monitoring disease severity, aggravates AAI and the application of intranasal PAMAM-G3 could potentially be a novel therapeutic intervention for AAI. Allergen stimulates the secretion of cell-free DNA (cfDNA) in both human and mouse airway. Intranasal polyamidoamine dendrimers-generation 3 (PAMAM-G3) scavenges cfDNA and alleviates allergic airway inflammation.

Efficient skin interactions of graphene derivatives: challenge, opportunity or both?

Interactions between graphene, with its wide deployment in consumer products, and skin, the body's largest organ and first barrier, are highly relevant with respect to toxicology and dermal delivery. In this work, interaction of polyglycerol-functionalized graphene sheets, with 200 nm average lateral size and different surface charges, and human skin was studied and their potential as topical delivery systems were investigated. While neutral graphene sheets showed no significant skin interaction, their positively and negatively charged counterparts interacted with the skin, remaining in the stratum corneum. This efficient skin interaction bears a warning but also suggests a new topical drug delivery strategy based on the sheets' high loading capacity and photothermal property. Therefore, the immunosuppressive drug tacrolimus was loaded onto positively and negatively charged graphene sheets, and its release measured with and without laser irradiation using liquid chromatography tandem-mass spectrometry. Laser irradiation accelerated the release of tacrolimus, due to the photothermal property of graphene sheets. In addition, graphene sheets with positive and negative surface charges were loaded with Nile red, and their ability to deliver this cargo through the skin was investigated. Graphene sheets with positive surface charge were more efficient than the negatively charged ones in enhancing Nile red penetration into the skin.

Polyglycerol-Amine Covered Nanosheets Target Cell-Free DNA to Attenuate Acute Kidney Injury.

Increased levels of circulating cell-free DNA (cfDNA) are associated with poor clinical outcomes in patients with acute kidney injury (AKI). Scavenging cfDNA by nanomaterials is regarded as a promising remedy for cfDNA-associated diseases, but a nanomaterial-based cfDNA scavenging strategy has not yet been reported for AKI treatment. Herein, polyglycerol-amine (PGA)-covered MoS2 nanosheets with suitable size are synthesized to bind negatively charged cfDNA in vitro, in vivo and ex vivo models. The nanosheets exhibit higher cfDNA binding capacity than polymer PGA and PGA-based nanospheres owing to the flexibility and crimpability of their 2D backbone. Moreover, with low cytotoxicity and mild protein adsorption, the nanosheets effectively reduced serum cfDNA levels and predominantly accumulated in the kidneys to inhibit the formation of neutrophil extracellular traps and renal inflammation, thereby alleviating both lipopolysaccharide and ischemia-reperfusion induced AKI in mice. Further, they decreased the serum cfDNA levels in samples from AKI patients. Thus, PGA-covered MoS2 nanosheets can serve as a potent cfDNA scavenger for treating AKI and other cfDNA-associated diseases. In addition, this work demonstrates the pivotal feature of a 2D sheet-like structure in the development of the cfDNA scavenger, which can provide a new insight into the future design of nanoplatforms for modulating inflammation.

Comparative Analysis of Nucleic Acid-Binding Polymers as Potential Anti-Inflammatory Nanocarriers.

Conventionally, nanocarriers are used to regulate the controlled release of therapeutic payloads. Increasingly, they can also be designed to have an intrinsic therapeutic effect. For example, a positively charged nanocarrier can bind damage-associated molecular patterns, inhibiting toll-like receptor (TLR) pathway activation and thus modulating inflammation. These nucleic acid-binding nanomaterials (NABNs), which scavenge pro-inflammatory stimuli, exist in diverse forms, ranging from soluble polymers to nanoparticles and 2D nanosheets. Unlike conventional drugs that primarily address inflammation symptoms, these NABPs target the upstream inflammation initiation pathway by removing the agonists responsible for inflammation. Many NABNs have demonstrated effectiveness in murine models of inflammatory diseases. However, these scavengers have not been systematically studied and compared within a single setting. Herein, we screen a subset of the most potent NABNs to define their relative efficiency in scavenging cell-free nucleic acids and inhibiting various TLR pathways. This study helps interpret existing in vivo results and provides insights into the future design of anti-inflammatory nanocarriers.

Design of therapeutic biomaterials to control inflammation.

Inflammation plays an important role in the response to danger signals arising from damage to our body and in restoring homeostasis. Dysregulated inflammatory responses occur in many diseases, including cancer, sepsis and autoimmunity. The efficacy of anti-inflammatory drugs, developed for the treatment of dysregulated inflammation, can be potentiated using biomaterials, by improving the bioavailability of drugs and by reducing side effects. In this Review, we first outline key elements and stages of the inflammatory environment and then discuss the design of biomaterials for different anti-inflammatory therapeutic strategies. Biomaterials can be engineered to scavenge danger signals, such as reactive oxygen and nitrogen species and cell-free DNA, in the early stages of inflammation. Materials can also be designed to prevent adhesive interactions of leukocytes and endothelial cells that initiate inflammatory responses. Furthermore, nanoscale platforms can deliver anti-inflammatory agents to inflammation sites. We conclude by discussing the challenges and opportunities for biomaterial innovations in addressing inflammation.

Screening of Tumor Antigens and Construction of Immune Subtypes for mRNA Vaccine Development in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: A growing number of clinical studies have confirmed that mRNA vaccines are effective in the treatment of malignant tumors; however, their efficacy in head and neck squamous cell carcinoma (HNSCC) has not been determined. This study aimed to identify the potential antigens of HNSCC for mRNA vaccine development and further distinguish the immune subtypes of HNSCC to select suitable patients for vaccination. METHODS: We obtained gene expression profiles and corresponding clinical information of HNSCC from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). We visualized the genetic alterations of potential antitumor antigens using cBioPortal and obtained the immune gene set from Immport. The correlation between the expression of the identified antigens and the infiltration of antigen-presenting cells was visualized by Tumor Immune Estimation Resource (TIMER). We evaluated the potential biological functions of different samples and described the immune landscape. RESULTS: Increased expression of three potential tumor antigens, CCR4, TMCO1, and SPACA4, associated with superior prognoses and infiltration of antigen-presenting cells, was identified in HNSCC. Three immune subtypes (C1-C3) with different molecular, cellular, and clinical characteristics were defined. Patients with C3 tumor had a better prognosis, representing an immune "cold" phenotype, which may be more suitable for mRNA vaccination. In addition, different immune characteristics were observed among the three immune subtypes, including markers of immune cells, mutation burden, expression of immune checkpoints, and immune modulators. Finally, the immune landscape of HNSCC showed a high degree of heterogeneity between individual patients. CONCLUSION: CCR4, TMCO1, and SPACA4 may be potential antigens for developing mRNA vaccines against HNSCC, especially for patients with C3 tumor. This study could provide a theoretical basis for the development of an mRNA vaccine against HNSCC.

A Versatile and Robust Platform for the Scalable Manufacture of Biomimetic Nanovaccines.

Biomimetic strategies are useful for designing potent vaccines. Decorating a nanoparticulate adjuvant with cell membrane fragments as the antigen-presenting source exemplifies, such as a promising strategy. For translation, a standardizable, consistent, and scalable approach for coating nanoadjuvant with the cell membrane is important. Here a turbulent mixing and self-assembly method called flash nanocomplexation (FNC) for producing cell membrane-coated nanovaccines in a scalable manner is demonstrated. The broad applicability of this FNC technique compared with bulk-sonication by using ten different core materials and multiple cell membrane types is shown. FNC-produced biomimetic nanoparticles have promising colloidal stability and narrow particle polydispersity, indicating an equal or more homogeneous coating compared to the bulk-sonication method. The potency of a nanovaccine comprised of B16-F10 cancer cell membrane decorating mesoporous silica nanoparticles loaded with the adjuvant CpG is then demonstrated. The FNC-fabricated nanovaccines when combined with anti-CTLA-4 show potency in lymph node targeting, DC antigen presentation, and T cell immune activation, leading to prophylactic and therapeutic efficacy in a melanoma mouse model. This study advances the design of a biomimetic nanovaccine enabled by a robust and versatile nanomanufacturing technique.

Dose-Dependent Carbon-Dot-Induced ROS Promote Uveal Melanoma Cell Tumorigenicity via Activation of mTOR Signaling and Glutamine Metabolism.

Uveal melanoma (UM) is the most common intraocular malignant tumor in adults and has a low survival rate following metastasis; it is derived from melanocytes susceptible to reactive oxygen species (ROS). Carbon dot (Cdot) nanoparticles are a promising tool in cancer detection and therapy due to their unique photophysical properties, low cytotoxicity, and efficient ROS productivity. However, the effects of Cdots on tumor metabolism and growth are not well characterized. Here, the effects of Cdots on UM cell metabolomics, growth, invasiveness, and tumorigenicity are investigated in vitro and in vivo zebrafish and nude mouse xenograft model. Cdots dose-dependently increase ROS levels in UM cells. At Cdots concentrations below 100 µg mL-1, Cdot-induced ROS promote UM cell growth, invasiveness, and tumorigenicity; at 200 µg mL-1, UM cells undergo apoptosis. The addition of antioxidants reverses the protumorigenic effects of Cdots. Cdots at 25-100 µg mL-1 activate Akt/mammalian target of rapamycin (mTOR) signaling and enhance glutamine metabolism, generating a cascade that promotes UM cell growth. These results demonstrate that moderate, subapoptotic doses of Cdots can promote UM cell tumorigenicity. This study lays the foundation for the rational application of ROS-producing nanoparticles in tumor imaging and therapy.

Biomimetic Diselenide-Bridged Mesoporous Organosilica Nanoparticles as an X-ray-Responsive Biodegradable Carrier for Chemo-Immunotherapy.

Chemotherapy causes off-target toxicity and is often ineffective against solid tumors. Targeted and on-demand release of chemotherapeutics remains a challenge. Here, cancer-cell-membrane-coated mesoporous organosilica nanoparticles (MONs) containing X-ray- and reactive oxygen species (ROS)-responsive diselenide bonds for controlled release of doxorubicin (DOX) at tumor sites are developed. DOX-loaded MONs coated with 4T1 breast cancer cell membranes (CM@MON@DOX) show greater accumulation at tumor sites and prolonged blood circulation time versus an uncoated control in mice bearing 4T1 orthotopic mammary tumors. Under low-dose X-ray radiation, the DOX-loaded MONs exhibit carrier degradation-controlled release via cleavage of diselenide bonds, resulting in DOX-mediated immunogenic cell death at the tumor site. Combination with a PD-L1 checkpoint blockade further enhances inhibition of tumor growth and metastasis with low systemic toxicity. Together, the findings show the promise of these biomimetic, radiation-responsive diselenide-bond-bridged MONs in chemo-immunotherapy.

Janus Nanobullets Combine Photodynamic Therapy and Magnetic Hyperthermia to Potentiate Synergetic Anti-Metastatic Immunotherapy.

Photodynamic therapy (PDT) is clinically promising in destructing primary tumors but ineffective against distant metastases. This study reports the use of immunogenic nanoparticles mediated combination of PDT and magnetic hyperthermia to synergistically augment the anti-metastatic efficacy of immunotherapy. Janus nanobullets integrating chlorine e6 (Ce6) loaded, disulfide-bridged mesoporous organosilica bodies with magnetic heads (M-MONs@Ce6) are tailored for redox/pH-triggered photosensitizer release accompanying their matrix degradation. Cancer cell membrane cloaking enables favorable tumor-targeted accumulation and prolonged blood circulation time of M-MONs@Ce6. The combination of PDT and magnetic hyperthermia has a strong synergy anticancer activity and simultaneously elicits a sequence of immunogenic cell death, resulting in synergistically tumor-specific immune responses. When combined with anti-CTLA-4 antibody, the biomimetic and biodegradable nanoparticle enables the notable eradication of primary and deeply metastatic tumors with low systematic toxicity, thus potentially advancing the development of combined hyperthermia, PDT, and checkpoint blockade immunotherapy to combat cancer metastasis.

Mechanistic Understanding of the Interactions between Nano-Objects with Different Surface Properties and α-Synuclein.

Aggregation of the natively unfolded protein α-synuclein (α-syn) is key to the development of Parkinson's disease (PD). Some nanoparticles (NPs) can inhibit this process and in turn be used for treatment of PD. Using simulation strategies, we show here that α-syn self-assembly is electrostatically driven. Dimerization by head-to-head monomer contact is triggered by dipole-dipole interactions and subsequently stabilized by van der Waals interactions and hydrogen bonds. Therefore, we hypothesized that charged nano-objects could interfere with this process and thus prevent α-syn fibrillation. In our simulations, positively and negatively charged graphene sheets or superparamagnetic iron oxide NPs first interacted with α-syn's N/C terminally charged residues and then with hydrophobic residues in the non-amyloid-ß component (61-95) region. In the experimental setup, we demonstrated that the charged nano-objects have the capacity not only to strongly inhibit α-syn fibrillation (both nucleation and elongation) but also to disaggregate the mature fibrils. Through the α-syn fibrillation process, the charged nano-objects induced the formation of off-pathway oligomers.

Multivalent Interactions between 2D Nanomaterials and Biointerfaces.

2D nanomaterials, particularly graphene, offer many fascinating physicochemical properties that have generated exciting visions of future biological applications. In order to capitalize on the potential of 2D nanomaterials in this field, a full understanding of their interactions with biointerfaces is crucial. The uptake pathways, toxicity, long-term fate of 2D nanomaterials in biological systems, and their interactions with the living systems are fundamental questions that must be understood. Here, the latest progress is summarized, with a focus on pathogen, mammalian cell, and tissue interactions. The cellular uptake pathways of graphene derivatives will be discussed, along with health risks, and interactions with membranes-including bacteria and viruses-and the role of chemical structure and modifications. Other novel 2D nanomaterials with potential biomedical applications, such as transition-metal dichalcogenides, transition-metal oxide, and black phosphorus will be discussed at the end of this review.