MicroRNA-induced reprogramming of tumor-associated macrophages for modulation of tumor immune microenvironment.

Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment and typically exhibit pro-tumoral phenotypes. TAMs overexpress the signal regulatory protein alpha (SIRPα) receptor on their surface, which interacts with CD47 on tumor cells to inhibit their phagocytic activity. In this study, we developed lipid nanoparticles modified with an anti-SIRPα antibody (aSIRPα) for the targeted delivery of microRNA-155 (miR155@aSIRPα-LNP) to TAMs, aiming to enhance their anti-tumoral phenotypes within the tumor microenvironment.

Anti-Inflammatory Macrophage-Derived Exosomes Modified With Self-Antigen Peptides for Treatment of Experimental Autoimmune Encephalomyelitis.

Current treatments for autoimmune diseases often involve broad-acting immunosuppressants, which carry risks such as infections and malignancies. This study investigates whether exosomes derived from anti-inflammatory macrophages (AE) and decorated with myelin oligodendrocyte glycoprotein (MOG) peptide (AE/M) can induce immune tolerance in autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis, serves as the autoimmune disease model.

Hybrid lipid nanoparticles with tumor antigen-primed dendritic cell membranes for post-surgical tumor immunotherapy.

Post-surgical tumor recurrence poses a major challenge in cancer treatment due to residual tumor cells and surgery-induced immunosuppression. Here, we developed hybrid nanoparticles, termed T-DCNPs, designed to promote antigen-specific activation of cytotoxic CD8+ T cells while concurrently inhibiting immunosuppressive pathways within the tumor microenvironment. T-DCNPs were formulated by co-extruding lipid nanoparticles containing a transforming growth factor β inhibitor with dendritic cells that were pre-treated with autologous neoantigens derived from surgically excised tumors.

NET formation-mediated in situ protein delivery to the inflamed central nervous system.

Delivering protein drugs to the central nervous system (CNS) is challenging due to the blood-brain and blood-spinal cord barrier. Here we show that neutrophils, which naturally migrate through these barriers to inflamed CNS sites and release neutrophil extracellular traps (NETs), can be leveraged for therapeutic delivery. Tannic acid nanoparticles tethered with anti-Ly6G antibody and interferon-β (aLy6G-IFNβ@TLP) are constructed for targeted neutrophil delivery.

Cell membrane-coated mRNA nanoparticles for enhanced delivery to dendritic cells and immunotherapy.

Cationic polymers such as polyethylenimine have been considered promising carriers for mRNA vaccines. However, their application is hindered by their inherent toxicity and a lack of targeted delivery capability. These issues need to be addressed to develop effective cancer vaccines.

Pathological Microenvironment-Remodeling Nanoparticles to Alleviate Liver Fibrosis: Reversing Hepatocytes-Hepatic Stellate Cells Malignant Crosstalk.

During the onset and malignant development of liver fibrosis, the pernicious interplay between damaged hepatocytes and activated hepatic stellate cells (HSCs) induce a self-perpetuating vicious cycle, deteriorating fibrosis progression and posing a grave threat to public health. The secretions released by damaged hepatocytes and activated HSCs interact through autocrine or paracrine mechanisms, involving multiple signaling pathways. This interaction creates a harsh microenvironment and weakens the therapeutic efficacy of single-cell-centric drugs.

Cytoskeleton-modulating nanomaterials and their therapeutic potentials.

The cytoskeleton, an intricate network of protein fibers within cells, plays a pivotal role in maintaining cell shape, enabling movement, and facilitating intracellular transport. Its involvement in various pathological states, ranging from cancer proliferation and metastasis to the progression of neurodegenerative disorders, underscores its potential as a target for therapeutic intervention. The exploration of nanotechnology in this realm, particularly the use of nanomaterials for cytoskeletal modulation, represents a cutting-edge approach with the promise of novel treatments.

Size-Dependent Effect of Indocyanine Green Nanoimaging Agent for Metastatic Lymph Node Detection.

Identification of metastatic lymph nodes is a crucial step in lymph node dissection to prevent further cancer spread and recurrence. However, the current limitations in metastatic lymph node detection often result in extensive resection of normal lymph nodes, leading to serious complications. The clinical application of indocyanine green (ICG) as a tool for lymph node detection is challenging because of its short plasma half-life and rapid light-induced decomposition and clearance.

Nanomodulator-Mediated Restructuring of Adipose Tissue Immune Microenvironments for Antiobesity Treatment.

In obesity, the interactions between proinflammatory macrophages and adipocytes in white adipose tissues are known to play a crucial role in disease progression by providing inflammatory microenvironments. Here, we report that the functional nanoparticle-mediated modulation of crosstalk between adipocytes and macrophages can remodel adipocyte immune microenvironments. As a functional nanomodulator, we designed antivascular cell adhesion molecule (VCAM)-1 antibody-conjugated and amlexanox-loaded polydopamine nanoparticles (VAPN).

RNA Nanomedicine: Delivery Strategies and Applications.

Delivery of RNA using nanomaterials has emerged as a new modality to expand therapeutic applications in biomedical research. However, the delivery of RNA presents unique challenges due to its susceptibility to degradation and the requirement for efficient intracellular delivery. The integration of nanotechnologies with RNA delivery has addressed many of these challenges.

Lysyl oxidase-responsive anchoring nanoparticles for modulation of the tumor immune microenvironment.

In the tumor microenvironment, lysyl oxidase (LOX) is known to play a key role in stabilizing the tumor extracellular matrix. Here, we designed LOX-responsive nanoparticles to interact with the collagen matrix of the tumor microenvironment. Collagen-coated and imiquimod-loaded polydopamine nanoparticles (CPN/IQ) could form crosslinked structures with the collagen matrix via LOX.

External cold atmospheric plasma-responsive on-site hydrogel for remodeling tumor immune microenvironment.

Although immunotherapy has recently emerged as a promising anti-tumor approach, it remains limited by the immunosuppressive tumor microenvironment. Cold atmospheric plasma irradiation can generate reactive oxygen species and trigger the presentation of tumor-associated antigens. Here, we exploited cold atmospheric plasma for on-site hydrogel application in the tumor environment, aiming to facilitate the sustainable uptake of tumor-associated antigens and nanoadjuvants by dendritic cells.

Tolerogenic Nanovaccine for Prevention and Treatment of Autoimmune Encephalomyelitis.

Herein, a tolerogenic nanovaccine is developed and tested on an animal model of multiple sclerosis. The nanovaccine is constructed to deliver the self-antigen, myelin oligodendrocyte glycoprotein (MOG) peptide, and dexamethasone on an abatacept-modified polydopamine core nanoparticle (AbaLDPN-MOG). AbaLDPN-MOG can target dendritic cells and undergo endocytosis followed by trafficking to lysosomes.

Nanomaterials for antigen-specific immune tolerance therapy.

Impairment of immune tolerance might cause autologous tissue damage or overactive immune response against non-pathogenic molecules. Although autoimmune disease and allergy have complicated pathologies, the current strategies have mainly focused on symptom amelioration or systemic immunosuppression which can lead to fatal adverse events. The induction of antigen-specific immune tolerance may provide therapeutic benefits to autoimmune disease and allergic response, while reducing nonspecific immune adverse responses.

Blood-declustering excretable metal clusters assembled in DNA matrix.

We report polymeric DNA-supported gold clusters that achieve interparticle plasmon-coupling, generate immunotherapeutic effects at the tumor tissue, but decluster in the bloodstream. As immunostimulating DNA, we used polyCpG DNA, which could act as a supporting matrix for metal clusters, enabling the clusters to decluster in the bloodstream. We constructed polyCpG-supported gold nanoclusters (AuPCN).

Sequential Nano-Penetrators of Capillarized Liver Sinusoids and Extracellular Matrix Barriers for Liver Fibrosis Therapy.

During liver fibrogenesis, liver sinusoidal capillarization and extracellular matrix (ECM) deposition construct dual pathological barriers to drug delivery. Upon capillarization, the vanished fenestrae in liver sinusoidal endothelial cells (LSECs) significantly hinder substance exchange between blood and liver cells, while excessive ECM further hinders the delivery of nanocarriers to activated hepatic stellate cells (HSCs). Herein, an efficient nanodrug delivery system was constructed to sequentially break through the capillarized LSEC barrier and the deposited ECM barrier.

In vivo fate and intracellular trafficking of vaccine delivery systems.

With the pandemic of severe acute respiratory syndrome coronavirus 2, vaccine delivery systems emerged as a core technology for global public health. Given that antigen processing takes place inside the cell, the intracellular delivery and trafficking of a vaccine antigen will contribute to vaccine efficiency. Investigations focusing on the in vivo behavior and intracellular transport of vaccines have improved our understanding of the mechanisms relevant to vaccine delivery systems and facilitated the design of novel potent vaccine platforms.

DNA-based artificial dendritic cells for in situ cytotoxic T cell stimulation and immunotherapy.

In immunotherapy, ex vivo stimulation of T cells requires significant resources and effort. Here, we report artificial dendritic cell-mimicking DNA microflowers (DM) for programming T cell stimulation in situ. To mimic dendritic cells, DNA-based artificial dendritic microflowers were constructed, surface-coated with polydopamine, and further modified with anti-CD3 and anti-CD28 antibodies to yield antibody-modified DM (DM-A).

Fibroblast activation protein activated antifibrotic peptide delivery attenuates fibrosis in mouse models of liver fibrosis.

In liver fibrosis, activated hepatic stellate cells are known to overexpress fibroblast activation protein. Here we report a targeted antifibrotic peptide-delivery system in which fibroblast activation protein, which is overexpressed in fibrotic regions of the liver, liberates the antifibrotic peptide melittin by cleaving a fibroblast activation protein-specific site in the peptide. The promelittin peptide is linked to pegylated and maleimide-functionalized liposomes, resulting in promelittin-modified liposomes.

Nanotherapeutics for immune network modulation in tumor microenvironments.

Immunotherapy has shown promise in cancer treatment, and is thus drawing increasing interest in this field. While the standard chemotherapy- and/or radiotherapy-based cancer treatments aim to directly kill cancer cells, immunotherapy uses host immune cell surveillance to fight cancer. In the tumor environment, there is a close relationship between tumor cells and the adjacent immune cells, which are largely suppressed by cancer-related regulation of immune checkpoints, immune-suppressive cytokines, and metabolic factors.