Amplifying glioblastoma immunotherapy: T cell shielding through Nitric oxide/reactive oxygen species scavenging nanoparticles Potentiates anti-PD-1.

Despite the success of immune checkpoint blockade (ICB) therapy in various cancers, its efficacy faces challenges in glioblastoma (GBM) due to the immunosuppressive cold-tumor microenvironment. The scarcity of tumor-infiltrating T cells and the suppression of T cell activity significantly limit therapeutic outcomes in GBM. Nitric oxide (NO) and reactive oxygen species (ROS) from tumor-associated myeloid cells (TAMCs) are key contributors to T cell suppression, reducing ICB therapy effectiveness.

Poly(β-amino ester) polymer library with monomer variation for mRNA delivery.

Non-viral vectors for mRNA delivery primarily include lipid nanoparticles (LNPs) and polymers. While LNPs are known for their high mRNA delivery efficiency, they can induce excessive immune responses and cause off-target effects, potentially leading to side effects. In this study, we aimed to explore polymer-based mRNA delivery systems as a viable alternative to LNPs, focusing on their mRNA delivery efficiency and potential application in mRNA vaccines.

Frequency-hopping along with resolution-turning for fast and enhanced reconstruction in ultrasound tomography.

The distorted Born iterative (DBI) method is considered to obtain images with high-contrast and resolution. Besides satisfying the Born approximation condition, the frequency-hopping (FH) technique is necessary to gradually update the sound contrast from the first iteration and progress to the actual sound contrast of the imaged object in subsequent iterations. Inspired by the fact that the higher the frequency, the higher the resolution.

Nitric oxide-scavenging hyaluronic acid nanoparticles for osteoarthritis treatment.

Osteoarthritis (OA) is a degenerative arthritis disease marked by inflammation, pain, and cartilage deterioration. Elevated nitric oxide (NO) levels play a pivotal role in mediating OA-related inflammation and are found in abundance within OA joints. This study introduces a NO-scavenging hyaluronic acid conjugate (HA-NSc) bearing both lubrication and anti-inflammatory properties for the treatment of osteoarthritis.

Dextran Sulfate Nanocarriers: Design, Strategies and Biomedical Applications.

Dextran sulfate (DXS) is a hydrophilic, non-toxic, biodegradable, biocompatible and safe biopolymer. These biomedically relevant characteristics make DXS a promising building block in the development of nanocarrier systems for several biomedical applications, including imaging and drug delivery. DXS polyanion can bind with metal oxide nanomaterials, biological receptors and therapeutic drug molecules.

Recent Advances in Biomedical Applications of Polymeric Nanoplatform Assisted with Two-Photon Absorption Process.

Polymers are well-recognized carriers useful for delivering therapeutic drug and imaging probes to the target specified in the defined pathophysiological site. The functional drug molecules and imaging agents were chemically attached or physically loaded in the carrier polymer matrix via cleavable spacers. Using appropriate targeting moieties, these polymeric carriers (PCs) loaded with functional molecules were designed to realize target-specific delivery at the cellular level.

Immunostimulation of tumor microenvironment by targeting tumor-associated macrophages with hypoxia-responsive nanocomplex for enhanced anti-tumor therapy.

Tumor-associated macrophages (TAMs), which dampen the therapeutic efficacy of cancer immunotherapy, are the key players in the immunosuppressive tumor microenvironment (TME). Therefore, reprogramming TAMs into tumoricidal M1 macrophages possesses considerable potential as a novel immunotherapy. However, the low bioavailability of polarization agents and limited accumulation of TAMs restrict their anti-tumor efficacy.

Eye Movement Signal Classification for Developing Human-Computer Interface Using Electrooculogram.

Human-computer interfaces (HCI) allow people to control electronic devices, such as computers, mouses, wheelchairs, and keyboards, by bypassing the biochannel without using motor nervous system signals. These signals permit communication between people and electronic-controllable devices. This communication is due to HCI, which facilitates lives of paralyzed patients who do not have any problems with their cognitive functioning.

Enzyme-Triggered Disassembly of Polymeric Micelles by Controlled Depolymerization via Cascade Cyclization for Anticancer Drug Delivery.

The high activity of specific enzymes in cancer has been utilized in cancer diagnosis, as well as tumor-targeted drug delivery. NAD(P)H:quinone oxidoreductase-1 (NQO1), an overexpressed enzyme in certain tumor types, maintains homeostasis and inhibits oxidative stress caused by elevated reactive oxygen species (ROS) in tumor cells. The activity of NQO1 in lung and liver cancer cells is increased compared to that in normal cells.

Polymer/Aptamer-Integrated Gold Nanoconstruct Suppresses the Inflammatory Process by Scavenging ROS and Capturing Pro-inflammatory Cytokine TNF-α.

In the present study, we report a rationally designed polymer/aptamer-integrated gold (Au) nanoconstruct capable of scavenging reactive oxygen species (ROS) and capturing tumor necrosis factor alpha (TNF-α) and investigate its potential as an anti-inflammatory agent for the treatment of peritonitis. By taking advantage of specific interactions between ATP and both ATP aptamer and polymeric phenylboronic acid (pPBA), we construct a unique polymer-coated Au nanoconstruct equipped with TNF-α aptamer and ATP aptamer. The formed phenylboronic ester and TNF-α aptamer in the nanoconstruct is capable of scavenging ROS and capturing of TNF-α, respectively.

Tumor Microenvironment Sensitive Nanocarriers for Bioimaging and Therapeutics.

The tumor microenvironment (TME), which is composed of cancer cells, stromal cells, immune cells, and extracellular matrices, plays an important role in tumor growth and progression. Thus, targeting the TME using a well-designed nano-drug delivery system is emerging as a promising strategy for the treatment of solid tumors. Compared to normal tissues, the TME presents several distinguishable physiological features such as mildly acidic pH, hypoxia, high level of reactive oxygen species, and overexpression of specific enzymes, that are exploited as stimuli to induce specific changes in the nanocarrier structures, and thereby facilitates target-specific delivery of imaging or chemotherapeutic agents for the early diagnosis or effective treatment, respectively.

Polymersomes with singlet oxygen-labile poly(β-aminoacrylate) membrane for NIR light-controlled combined chemo-phototherapy.

Engineering the membrane of the polymersomes with biologically relevant stimuli-responsive units enables spatial and temporal controlled drug release for effective therapy. Herein, we introduce a new-type of polymersomes featuring reactive oxygen species singlet oxygen (O)-labile membrane by employing a versatile stereoregular amphiphilic poly(ethylene glycol)-block-poly(β-aminoacrylate)-block-poly(ethylene glycol) copolymers, which are synthesized through a facile one pot modular amino-alkynoate click polymerization between secondary amines and activated alkynes. These polymersomes readily co-encapsulate an anticancer drug doxorubicin (DOX) and a near infrared (NIR) photosensitizer IR-780 with hydrophobic characteristics in the membrane, and the resulting polymersomes show efficient uptake by the tumor cells.

Harnessing the Formation of Natural Killer-Tumor Cell Immunological Synapses for Enhanced Therapeutic Effect in Solid Tumors.

The formation of an immunological synapse (IS) on recognition of a cancer cell is the main mechanism underlying the natural killer (NK)-cell-mediated killing of tumor cells. Herein, an integrative strategy for cancer therapy against solid tumors is reported, in which alterations in the cleft of IS, following the secretion of acidic granular content, are utilized as a trigger for the delivery of chemotherapeutic drugs. NK cells are decorated with the IS-environment-responsive micellar system to ensure the release of the payload when they attack cancer cells.

A cyotosol-selective nitric oxide bomb as a new paradigm of an anticancer drug.

We have reported rational design of a polymeric NO delivery micelle as a cytosol-selective NO bomb. Protected NO-donors are released from the micelle under endolysosomal conditions, and then deprotected by cytosolic glutathione. Cytosol-selective NO delivery facilitates significant tumor regression without the aid of other therapeutic modalities even in intravenous administrations.

Tumor vasodilation by N-Heterocyclic carbene-based nitric oxide delivery triggered by high-intensity focused ultrasound and enhanced drug homing to tumor sites for anti-cancer therapy.

Nitric oxide (NO) is widely known as an effective vasodilator at low concentrations. Drug delivery systems combined with NO can dilate blood vessels surrounding tumor tissues, and the drug accumulation in tumors is accelerated by the enhanced permeability and retention effect, leading to an improvement in the anti-tumor effect. N-heterocyclic carbene-based NO donors (e.

Miktoarm Amphiphilic Block Copolymer with Singlet Oxygen-Labile Stereospecific β-Aminoacrylate Junction: Synthesis, Self-Assembly, and Photodynamically Triggered Drug Release.

Incorporation of a desired stimuli-responsive unit in a stereospecific manner at the specific location within a nonlinear block copolymer architecture is a challenging task in synthetic polymer chemistry. Herein, we report a facile and versatile method to synthesize AB miktoarm block copolymers bearing a singlet oxygen (O)-labile regio and stereospecific β-aminoacrylate linkage with 100% E-configuration at the junction via a combination of amino-yne click chemistry and ring opening polymerization. Using this strategy, a series of O-responsive AB amphiphilic miktoarm (MA) copolymers composed of hydrophilic polyethylene glycol (PEG) as the A constituent and hydrophobic polycaprolactone (PCL) as the B constituent (MA-PEG- b-PCL) was synthesized by varying the block length of PCL.

Synthesis and Characterization of Nitric Oxide-Releasing Platinum(IV) Prodrug and Polymeric Micelle Triggered by Light.

Herein, we report the proof of concept of photoresponsive chemotherapeutics comprising nitric oxide-releasing platinum prodrugs and polymeric micelles. Photoactivatable nitric oxide-releasing donors were integrated into the axial positions of a platinum(IV) prodrug, and the photolabile hydrophobic groups were grafted in the block copolymers. The hydrophobic interaction between nitric oxide donors and the photolabile groups allowed for the loading of platinum drugs and nitric oxide-releasing donors in the photolabile polymeric micelles.

Reactive-Oxygen-Species-Responsive Drug Delivery Systems: Promises and Challenges.

Given the increasing evidence indicates that many pathological conditions are associated with elevated reactive oxygen species (ROS) levels, there have been growing research efforts focused on the development of ROS-responsive carrier systems because of their promising potential to realize more specific diagnosis and effective therapy. By judicious utilization of ROS-responsive functional moieties, a wide range of carrier systems has been designed for ROS-mediated drug delivery. In this review article, insights into design principle and recent advances on the development of ROS-responsive carrier systems for drug delivery applications are provided alongside discussion of their in vitro and in vivo evaluation.

Visible light-induced singlet oxygen-mediated intracellular disassembly of polymeric micelles co-loaded with a photosensitizer and an anticancer drug for enhanced photodynamic therapy.

Herein, we report a biocompatible amphiphilic block copolymer micelle bearing a singlet oxygen-sensitive vinyldithioether cleavable linker at the core-shell junction, which undergoes singlet oxygen-mediated photocleavage in the presence of visible light. The micelle facilitates the light-responsive release of singlet oxygen and an anticancer drug for enhanced photodynamic therapy.

Hyaluronic acid-based conjugates for tumor-targeted drug delivery and imaging.

In recent years, hyaluronic acid (HA) has attracted significant interest in development of drug delivery systems because of its intrinsic physicochemical and biological properties, including water solubility, viscoeleasticity, non-immunogenicity, biocompatibility, and biodegradability. In addition, HA has the ability to selectively bind specific receptors on the disease-related cells such as cancer cells and activated macrophages, followed by receptor-mediated endocytosis. Owing to these unique features, HA has been extensively used for development of the targetable carriers to deliver the therapeutic and imaging agents.

A platform for nitric oxide delivery.

Nitric oxide (NO) is one of the structurally smallest pharmaceutical molecules, which shows great potential as an anti-restenosis, wound healing, anticancer, and antibacterial agent. To date, while most of the studies have focused mainly on demonstrating the versatility of the NO-releasing materials, little effort has been made on developing successful NO-delivery strategies for advancing NO-mediated therapy. Thus, the quest for a rationally designed NO-delivery system is becoming one of the important issues in the biomedical applications of NO.

Dextran sulfate-coated superparamagnetic iron oxide nanoparticles as a contrast agent for atherosclerosis imaging.

The hallmark of atherosclerosis in its early pathogenic process is the overexpression of class A scavenger receptors (SR-A) by activated macrophages. In this study, dextran sulfate-coated superparamagnetic iron oxide nanoparticles (DS-SPIONs), as a magnetic resonance (MR) imaging contrast agent of atherosclerosis, was prepared via the facile co-precipitation method using a versatile double-hydrophilic block copolymer comprising of a DS segment (ligand for SR-A) and a poly(glyclerol methacrylate) segment (SPIONs surface-anchoring unit). The physicochemical properties of the DS-SPIONs were investigated using various instruments.

Cyclodextrin-based nanocomplexes for sustained delivery of human growth hormone.

The use of human growth hormone (hGH) as a therapeutic protein has been limited by its instability in biological fluids and short biological half-life in vivo. In this study, glycol chitosan (GC) bearing beta-cyclodextrin (GC-betaCD) as the carrier of hGH was synthesized by the covalent attachment of a carboxymethyl derivative of betaCD to the GC backbone via amide bond formation. The GC-betaCD conjugate could form self-assembled nanoparticles (340 nm in mean diameter) in an aqueous solution, resulting from hydrogen bonding among betaCDs at the backbone of the conjugate.

Carboxymethyl dextran-cyclodextrin conjugate as the carrier of doxorubicin.

The carboxymethyl dextran-y-cyclodextrin (CMD-yCD) conjugate was prepared as the carrier for the delivery of the poorly water-soluble anticancer drug, doxorubicin (DOX). The conjugate could form self-assembled nanoparticles (315 nm in diameter) in an aqueous solution, which might be due to the hydrogen bonding among yCD molecules in the conjugate. DOX was effectively encapsulated into CMD-yCD nanoparticles (CMD-NPs) by the emulsion method.