Roseburia intestinalis-derived extracellular vesicles ameliorate colitis by modulating intestinal barrier, microbiome, and inflammatory responses.

Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent gastrointestinal inflammation, lacking a precise aetiology and definitive cure. The gut microbiome is vital in preventing and treating IBD due to its various physiological functions. In the interplay between the gut microbiome and human health, extracellular vesicles secreted by gut bacteria (BEVs) are key mediators.

Nanoengineered Polymeric RNA Nanoparticles for Controlled Biodistribution and Efficient Targeted Cancer Therapy.

RNA nanotechnology, including rolling circle transcription (RCT), has gained increasing interest as a fascinating siRNA delivery nanoplatform for biostable and tumor-targetable RNA-based therapies. However, due to the lack of fine-tuning technologies for RNA nanostructures, the relationship between physicochemical properties and siRNA efficacy of polymeric siRNA nanoparticles (PRNs) with different sizes has not yet been fully elucidated. Herein, we scrutinized the effects of size/surface chemistry-tuned PRNs on the biological and physiological interactions with tumors.

Mucoadhesive chitosan microcapsules for controlled gastrointestinal delivery and oral bioavailability enhancement of low molecular weight peptides.

A bioactive compound, collagen peptide (CP), is widely used for biological activities such as anti-photoaging and antioxidant effects, with increased oral bioavailability because of its low molecular weight and high hydrophilicity. However, controlling release time and increasing retention time in the digestive tract for a more convenient oral administration is still a challenge. We developed CP-loaded chitosan (CS) microcapsules via strong and rapid ionic gelation using a highly negative phytic acid (PA) crosslinker.

Crystallinity-tuned ultrasoft polymeric DNA networks for controlled release of anticancer drugs.

Despite the vast interest in utilizing rolling circle amplification (RCA)-based DNA networks for bioapplications, precise control of the mechanical and physicochemical properties is highly challenging. To address this concern, we aimed to develop ultrasoft self-supporting polymerized DNA networks (pDNets) of variable crystallinities to manipulate sequence-mediated drug release efficiency. A controlled ratio of the inorganic magnesium pyrophosphate (MgPPi) crystal to the organic polymeric DNA resulted in the synthesis of pDNets of various nanoporosities.

Hyaluronic Acid Nanoparticles as a Topical Agent for Treating Psoriasis.

Although conventional topical approaches for treating psoriasis have been offered as an alternative, there are still unmet medical needs such as low skin-penetrating efficacy and off-target adverse effects. A hyaluronic acid nanoparticle (HA-NP) formed by self-assembly of HA-hydrophobic moiety conjugates has been broadly studied as a nanocarrier for long-term and target-specific delivery of drugs, owing to their excellent physicochemical and biological characteristics. Here, we identify HA-NPs as topical therapeutics for treating psoriasis using skin penetration studies and psoriasis animal models.

Plant-derived nanovesicles: Current understanding and applications for cancer therapy.

Plant-derived vesicles (PDVs) are membranous structures that originate from plant cells and are responsible for multiple physiological and pathological functions. In the last decade, PDVs have gained much attention for their involvement in different biological processes, including intercellular communication and defense response, and recent scientific evidence has opened a new avenue for their applications in cancer treatment. Nevertheless, much remains unknown about these vesicles, and current research remains inconsistent.

Discovery and Photoisomerization of New Pyrrolosesquiterpenoids Glaciapyrroles D and E, from Deep-Sea Sediment sp.

Two new pyrrolosesquiterpenes, glaciapyrroles D () and E () were discovered along with the previously reported glaciapyrrole A () from sp. GGS53 strain isolated from deep-sea sediment. This study elucidated the planar structures of and using nuclear magnetic resonance (NMR), mass spectrometry (MS), ultraviolet (UV), and infrared (IR) spectroscopic data.

Surface-Functionalized Polymeric siRNA Nanoparticles for Tunable Targeting and Intracellular Delivery to Hematologic Cancer Cells.

To date, the application of RNA therapeutics to hematologic malignancies has been challenging owing to the resistance of blood cancer cells against conventional transfection methods. Herein, triple-targeting moiety-functionalized polymeric small interfering RNA (siRNA) nanoparticles were systematically developed for efficient targeted delivery of RNA therapeutics to hematologic cancer cells. Polymeric siRNAs were synthesized using rolling circle transcription and were surface-functionalized with three types of targeting moieties─a natural ligand and two additional combinations of cell-specific antibodies─for tunable targetability.

Emerging nanoformulation strategies for phytocompounds and applications from drug delivery to phototherapy to imaging.

Over thousands of years, natural bioactive compounds derived from plants (bioactive phytocompounds, BPCs) have been used worldwide to address human health issues. Today, they are a significant resource for drug discovery in the development of modern medicines. Although many BPCs have promising biological activities, most of them cannot be effectively utilized in drugs for therapeutic applications because of their inherent limitations of low solubility, structural instability, short half-life, poor bioavailability, and non-specific distribution to organs.

Self-assembled hyaluronic acid nanoparticles for osteoarthritis treatment.

Although osteoarthritis (OA) is the most prevalent degenerative joint disease, there is no effective disease-modifying therapy. We report an empty self-assembled hyaluronic acid nanoparticle (HA-NP) as a potential therapeutic agent for OA treatment. In mouse primary articular chondrocytes, HA-NPs blocked the receptor-mediated cellular uptake of free low-molecular-weight HA, and the cellular uptake of HA-NPs increased by ectopic expression of CD44, using an adenoviral delivery system (Ad-Cd44).

Advances in Nanomaterial-Mediated Photothermal Cancer Therapies: Toward Clinical Applications.

Photothermal therapy (PTT) has attracted extensive research attention as a noninvasive and selective treatment strategy for numerous cancers. PTT functions via photothermal effects induced by converting light energy into heat on near-infrared laser irradiation. Despite the great advances in PTT for cancer treatment, the photothermal therapeutics using laser devise only or non-specific small molecule PTT agents has been limited because of its low photothermal conversion efficiency, concerns about the biosafety of the photothermal agents, their low tumor accumulation, and a heat resistance of specific types of cancer.

Bioorthogonally surface-edited extracellular vesicles based on metabolic glycoengineering for CD44-mediated targeting of inflammatory diseases.

Extracellular vesicles (EVs) are essential mediators in intercellular communication that have emerged as natural therapeutic nanomedicines for the treatment of intractable diseases. Their therapeutic applications, however, have been limited by unpredictable in vivo biodistribution after systemic administration. To control the in vivo fate of EVs, their surfaces should be properly edited, depending on the target site of action.

Self-assembled hyaluronic acid nanoparticle suppresses fat accumulation via CD44 in diet-induced obese mice.

Obesity, a major risk factor for type 2 diabetes and cardiovascular diseases, is characterized by an abnormal expansion of adipose tissue. Herein, we investigated the potential of hyaluronic acid nanoparticles (HA-NPs) as therapeutics to treat obesity-related diseases by assessing the in vitro and in vivo effects of HA-NPs on adipogenesis and lipogenesis. Treatment of 3T3-L1 preadipocytes with HA-NPs resulted in a dose-dependent suppression of adipogenesis and lipid accumulation, and decreased the expression of key adipogenic and lipogenic regulators.

Human adipose stem cell-derived extracellular nanovesicles for treatment of chronic liver fibrosis.

Liver fibrosis is an excessive wound healing process that occurs in response to liver damage depending on underlying aetiologies. Currently, there are no effective therapies and FDA-approved therapeutics for the treatment of liver fibrosis except liver transplantation. Multipotent adipose-derived stem cells (ADSCs) have received significant attention as regenerative medicine for liver fibrosis owing to their advantages over stem cells with other origins.

Hypoxia-Responsive Mesoporous Nanoparticles for Doxorubicin Delivery.

Hypoxia, or low oxygen tension, is a common feature of solid tumors. Here, we report hypoxia-responsive mesoporous silica nanoparticles (HR-MSNs) with a 4-nitroimidazole-β-cyclodextrin (NI-CD) complex that is acting as the hypoxia-responsive gatekeeper. When these CD-HR-MSNs encountered a hypoxic environment, the nitroimidazole (NI) gatekeeper portion of CD-HR-MSNs disintegrated through bioreduction of the hydrophobic NI state to the hydrophilic NI state.

Hyaluronic Acid-Based Activatable Nanomaterials for Stimuli-Responsive Imaging and Therapeutics: Beyond CD44-Mediated Drug Delivery.

There is a rapidly increasing interest in developing stimuli-responsive nanomaterials for treating a variety of diseases. By enabling the activation of function locally at the sites of interest, it is possible to increase therapeutic efficacy significantly while simultaneously reducing adverse side effects. While there are many sophisticated nanomaterials available, they are often highly complex and not easily transferrable to industrial scales and clinical settings.

ROS-responsive mesoporous silica nanoparticles for MR imaging-guided photodynamically maneuvered chemotherapy.

Mesoporous silica nanoparticles (MSNs) with stimuli-responsive gatekeepers have been extensively investigated for controlled drug delivery at the target sites. Herein, we developed reactive oxygen species (ROS)-responsive MSNs (R-MSNs), consisting of a gadolinium (Gd)-DOTA complex as the ROS-responsive gatekeeper and polyethylene glycol (PEG)-conjugated chlorin e6 as the ROS generator, for magnetic resonance (MR) imaging-guided photodynamic chemotherapy. Doxorubicin (DOX), chosen as an anticancer drug, was physically encapsulated into DOTA-conjugated MSNs, followed by chemical crosslinking via the addition of GdCl3.

Self-assembled hyaluronic acid nanoparticles: Implications as a nanomedicine for treatment of type 2 diabetes.

Self-assembled hyaluronic acid nanoparticles (HA-NPs) have been extensively investigated for biomedical and pharmaceutical applications owing to their biocompatibility and receptor-binding properties. Here, we report that an empty HA-NP itself not bearing any drug has therapeutic effects on adipose tissue inflammation and insulin resistance. HA-NPs inhibited not only the receptor-mediated internalization of low-molecular-weight (LMW) free HA but also LMW free HA-induced pro-inflammatory gene expression in mouse primary bone marrow-derived macrophages (BMDMs) isolated from wild-type mice, but not in CD44-null (CD44-/-) BMDMs.

Carboxymethyl dextran-based hypoxia-responsive nanoparticles for doxorubicin delivery.

In an attempt to develop the hypoxia-responsive nanoparticles for cancer therapy, a polymer conjugate, consisting of carboxymethyl dextran (CMD) and black hole quencher 3 (BHQ3), was prepared. The polymer conjugate can self-assemble into nanoparticles (CMD-BHQ3 NPs) under aqueous conditions. The anticancer drug, doxorubicin (DOX), was loaded in CMD-BHQ3 NPs to prepare DOX@CMD-BHQ3 NPs.

Gold-stabilized carboxymethyl dextran nanoparticles for image-guided photodynamic therapy of cancer.

Photodynamic therapy (PDT) has been extensively investigated to treat cancer since it induces cell death through the activation of photosensitizers by light. However, its success has been hampered by the insufficient selectivity of photosensitizers to tumor tissues. In an attempt to increase the therapeutic efficacy of PDT by targeting the photosensitizer specifically to the tumor site, we prepared chlorin e6 (Ce6)-loaded gold-stabilized carboxymethyl dextran nanoparticles (Ce6-GS-CNPs).

Endogenous inspired biomineral-installed hyaluronan nanoparticles as pH-responsive carrier of methotrexate for rheumatoid arthritis.

Methotrexate (MTX), an anchor drug for rheumatoid arthritis (RA), has been suffered from refractoriness and high toxicity limiting effective dosage. To mitigate these challenges, the ability to selectively deliver MTX to arthritis tissue is a much sought-after modality for the treatment of RA. In this study, we prepared mineralized nanoparticles (MP-HANPs), composed of PEGylated hyaluronic acid (P-HA) as the hydrophilic shell, 5β-cholanic acid as the hydrophobic core, and calcium phosphate (CaP) as the pH-responsive mineral.

In vivo visualization of endogenous miR-21 using hyaluronic acid-coated graphene oxide for targeted cancer therapy.

Oncogene-targeted nucleic acid therapy has been spotlighted as a new paradigm for cancer therapeutics. However, in vivo delivery issues and uncertainty of therapeutic antisense drug reactions remain critical hurdles for a successful targeted cancer therapy. In this study, we developed a fluorescence-switchable theranostic nanoplatform using hyaluronic acid (HA)-conjugated graphene oxide (GO), which is capable of both sensing oncogenic miR-21 and inhibiting its tumorigenicity simultaneously.

Gold-Nanoclustered Hyaluronan Nano-Assemblies for Photothermally Maneuvered Photodynamic Tumor Ablation.

Optically active nanomaterials have shown great promise as a nanomedicine platform for photothermal or photodynamic cancer therapies. Herein, we report a gold-nanoclustered hyaluronan nanoassembly (GNc-HyNA) for photothermally boosted photodynamic tumor ablation. Unlike other supramolecular gold constructs based on gold nanoparticle building blocks, this system utilizes the nanoassembly of amphiphilic hyaluronan conjugates as a drug carrier for a hydrophobic photodynamic therapy agent verteporfin, a polymeric reducing agent, and an organic nanoscaffold upon which gold can grow.

Zwitterionic mesoporous nanoparticles with a bioresponsive gatekeeper for cancer therapy.

Unlabelled: To enhance cellular uptake and site-specific drug release in the tumor microenvironment, zwitterionic mesoporous silica nanoparticles (Z-MSN) were prepared by introducing a bioresponsive gatekeeper composed of negatively charged carboxylic groups and positively charged quaternary amine groups. When these Z-MSN encountered a mildly acidic environment, their surface charge readily switched from negative to positive by cleavage of an acid-labile maleic amide linkage, thus allowing for effective cellular uptake into tumor tissue. Doxorubicin (DOX) encapsulated in Z-MSN was not significantly released in physiological conditions (pH 7.

A pH-responsive carboxymethyl dextran-based conjugate as a carrier of docetaxel for cancer therapy.

Although docetaxel is available for the treatment of various cancers, its clinical applications are limited by its poor water solubility and toxicity to normal cells, resulting in severe adverse effects. In this study, we synthesized a polymeric conjugate with an acid-labile ester linkage, consisting of carboxymethyl dextran (CMD) and docetaxel (DTX), as a potential anticancer drug delivery system. The conjugate exhibited sustained release of DTX in physiological buffer (pH 7.