Redox-responsive Polymer Research Articles

Intratumoral delivery of Mitomycin C using bio-responsive Gellan Gum Nanogel: In-vitro evaluation and enhanced chemotherapeutic efficacy.

Intratumoral drug delivery systems hold immense promise in overcoming the limitations of conventional IV chemotherapy, particularly in enhancing therapeutic efficacy and minimizing systemic side effects. In this study, we introduce a novel redox-responsive intratumoral nanogel system that combines the biocompatibility of natural polysaccharides with the tailored properties of synthetic polymers. The nanogel features a unique cross-linked architecture incorporating redox-sensitive segments, designed to leverage the elevated glutathione levels in the tumor microenvironment for controlled drug release. Synthesis was performed using a microwave-assisted free radical polymerization technique, which facilitated efficient and rapid cross-linking. A Quality by Design strategy was implemented to optimize key parameters, ensuring the nanogel's suitability for intratumoral delivery, including ideal injectability, viscosity, and drug release characteristics. Mitomycin C (MMC), a chemotherapeutic agent effective against hypoxic tumor cells, was efficiently loaded within the cross-linked nanogel. Optimal stability and drug loading were achieved at a 2:1 nanogel/MMC ratio. The nanogel's structure and composition were confirmed using elemental analysis, FTIR, NMR spectroscopy, and XRD. Stability studies demonstrated its robustness in simulated physiological conditions. In vitro evaluations revealed enhanced cellular uptake of the MMC-loaded nanogel, leading to effective cell cycle arrest, mitochondrial membrane potential disruption, and apoptosis, Co-localization studies with Lysotracker Green, a lysosomal marker, revealed that the nanogels were trafficked to lysosomes. Pharmacokinetic analysis showed significantly reduced systemic exposure (lower plasma Cmax) compared to intravenous administration, while biodistribution studies using IVIS imaging demonstrated prolonged retention of the nanogel within tumor tissues. In vivo studies using a 4T1 xenograft mouse model highlighted the superior antitumor efficacy of the intratumoral nanogel system compared to free MMC. The nanogel treatment resulted in significant tumor volume reduction, minimal changes in body weight, and reduced lung metastasis, as confirmed by histological analysis (HE staining). Ki67 and TUNEL assays of tumor tissues further substantiated the nanogel's ability to suppress proliferation and induce apoptosis. These outcomes directly correlate with our goal of using a redox responsive nanogel system to improve localized drug delivery and minimize systemic side effects. This biodegradable, redox-responsive polymer system represents a significant advance in nanomedicine, offering a promising platform for safe and effective localized cancer therapy.

Superparamagnetic iron oxide nanoparticles functionalized with on-demand redox-responsive contractible coordination polymer brush as molecular actuator driven by π-dimerization

Nanomachines require molecular actuators to be coupled to a condensed phase. In this work, a redox responsive 1D contractible coordination polymer (ZnL) used as non-interlocked actuator is grafted onto superparamagnetic iron oxide nanoparticles (SPIONs) in a brush-like configuration. Oxidized rod-like ZnL oligomers have ability to reversibly self-fold upon reduction via π-dimerization of their bis-viologen units. Unlike in usual responsive brushes, ZnL chains behave individually, generating spatially controlled mechanical motion at nanoparticle surface associated to significant variations of particle diameters. ZnL oligomers were “grafted to” SPIONs in a single step. Reduction of colloidal dispersions was perform by visible light illumination with the help of a photoreductant. π-dimerization was assessed by UV–vis–NIR and reversible contraction of ZnL brush was characterized by DLS. Effects of ZnL chains length and grafting density on mechanism and performance of contractibility were studied. ZnL brush can alternately be contracted and extended with excellent reversibility. Combined UV–vis–NIR, DLS and TGA analyses demonstrate that π-dimerization is only intramolecular and that chains behave as independent actuators. Maximal contraction of 22 nm is obtained for largest particles (DH = 86 nm). Full to partial contraction of the brush depends on grafting density with a threshold at ≈ 47 chains per particle.

Redox-responsive polymer micelles co-encapsulating immune checkpoint inhibitors and chemotherapeutic agents for glioblastoma therapy

Immunotherapy with immune checkpoint blockade (ICB) for glioblastoma (GBM) is promising but its clinical efficacy is seriously challenged by the blood-tumor barrier (BTB) and immunosuppressive tumor microenvironment. Here, anti-programmed death-ligand 1 antibodies (aPD-L1) are loaded into a redox-responsive micelle and the ICB efficacy is further amplified by paclitaxel (PTX)-induced immunogenic cell death (ICD) via a co-encapsulation approach for the reinvigoration of local anti-GBM immune responses. Consequently, the micelles cross the BTB and are retained in the reductive tumor microenvironment without altering the bioactivity of aPD-L1. The ICB efficacy is enhanced by the aPD-L1 and PTX combination with suppression of primary and recurrent GBM, accumulation of cytotoxic T lymphocytes, and induction of long-lasting immunological memory in the orthotopic GBM-bearing mice. The co-encapsulation approach facilitating efficient antibody delivery and combining with chemotherapeutic agent-induced ICD demonstrate that the chemo-immunotherapy might reprogram local immunity to empower immunotherapy against GBM.

Antitumor effects of redox-responsive nanoparticles containing platinum（Ⅳ）in ovarian cancer

Objectives: To explore the antitumor effects of redox-responsive nanoparticles containing platinum(Ⅳ)-NP@Pt(Ⅳ) in ovarian cancer. Methods: Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(Ⅳ)-Pt(Ⅳ) can self-assemble into NP@Pt(Ⅳ). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(Ⅳ) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(Ⅳ) and NP@Pt(Ⅳ). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(Ⅳ) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(Ⅳ). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured. Results: The platinum release of NP@Pt(Ⅳ) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment (P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(Ⅳ) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(Ⅳ) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, P＜0.05). The half inhibitory concentrations of NP@Pt(Ⅳ) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 μmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 μmol/L) and cisplatin (5.21, 11.85, and 71.98 μmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(Ⅳ) was (33.91±3.80)%, which was significantly higher than that of Pt(Ⅳ) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, P＜0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(Ⅳ) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm3, which was significantly lower than those in control group [(1 349±161) mm3, P<0.001] and cisplatin group [(715±293) mm3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(Ⅳ) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(Ⅳ) compared with cisplatin. The change in body weight of mice in NP@Pt(Ⅳ) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining. Conclusion: Redox-responsive NP@Pt(Ⅳ), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.

Recent Advances in pH and Redox Responsive Polymer Nanocomposites for Cancer Therapy

Cancer therapy currently focuses on personalized targeted treatments. A promising approach uses stimuli-responsive biomaterials for site-specific drug release, such as pH- and redox-triggered polymer nanocomposites. These materials respond to the tumor microenvironment, enhance efficacy, and reduce off-target effects. Cancer cells with anomalous properties such as acidic cytosolic pH and elevated redox potential are targeted by these biomaterials. An imbalance in ions and biological thiols in the cytoplasm contributes to tumor growth. Functionalized polymer nanocomposites with large surface areas and specific targeting outperform conventional small-molecule materials. To overcome problems such as low bioavailability, uncontrolled drug release, and poor cell penetration, multifunctional nanomaterials make it easier for drugs to enter certain cellular or subcellular systems. High therapeutic efficacy is achieved through surface functionalization, site-specific targeting, and the use of stimuli-responsive components. In particular, pH and redox dual-stimuli-based polymeric nanocomposites for cancer therapeutics have scarcely been reported. This article provides recent progress in pH- and redox-responsive polymer nanocomposites for site-specific drug delivery in cancer therapy. It explores the design principles, fabrication methods, mechanisms of action, and prospects of these dual-stimuli-responsive biomaterials.

Abstract A032: Cell membrane coated- Biomimetic biodegradable nanoparticles for tumor targeted delivery of THP-doxorubicin using polylactic acid based redox responsive polymer

Abstract Chemotherapy is a widely used systemic treatment modality for cancer treatment as it kills the rapidly dividing cells. However, the administered chemo-drugs cause systemic toxicity, have fast degradation rate at physiological conditions hence low bioavailability and poor tumor accumulation. These shortcomings can be mitigated by the use of tumor targeting drug delivery systems. The nanoparticles can further be tailor made according to physiological conditions of the tumor microenvironment. Herein, the redox responsive polymer has been synthesized by introducing the disulphide linkage in the polymer. The drug release profile indicated the release of the drug is more efficient in presence of 10mM Dithiothreitol(reducing agent for disulphide linkage) when compared to 0mM dithiothreitol. In this context, this study investigates the therapeutic efficacy of THP-doxorubicin encapsulated in polylactic acid based redox responsive nanoparticle(NP) whose surface have been modified with tumor (4T1) and macrophage (J774) cell membranes. The coated cell membrane provides advantages such as immune escape, long blood circulation time, specific molecular recognition and cell targeting. The prepared nanoparticles have a hydrodynamic size of 210±10 nm with zeta potential of -30±3 mV. The cellular internalization studies of free drug vs the cell membrane coated NPs (CMNPs) were done and it was confirmed that CMNPs were internalized more efficiently in one hour drug incubation study. The same was confirmed when cancer cell proliferation inhibition assay was done, and half maximal inhibitory concentration of free drug, uncoated NPs and CMNPs were 0.31µM , 0.463µM and 0.137µM respectively. This study provides the synthesis and characterization of redox responsive polymer, preparation of cell membrane coated nanoparticles and in-vitro studies for the same. This study has a future scope in the field of personalized medicine at much cheaper price when compared to active targeting methods by antibodies, CART, proteins etc. Citation Format: Harshdeep Kaur, Harpal Singh, Neetu Singh. Cell membrane coated- Biomimetic biodegradable nanoparticles for tumor targeted delivery of THP-doxorubicin using polylactic acid based redox responsive polymer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A032.

The role of smart polymeric biomaterials in bone regeneration: a review.

Addressing critical bone defects necessitates innovative solutions beyond traditional methods, which are constrained by issues such as immune rejection and donor scarcity. Smart polymeric biomaterials that respond to external stimuli have emerged as a promising alternative, fostering endogenous bone regeneration. Light-responsive polymers, employed in 3D-printed scaffolds and photothermal therapies, enhance antibacterial efficiency and bone repair. Thermo-responsive biomaterials show promise in controlled bioactive agent release, stimulating osteocyte differentiation and bone regeneration. Further, the integration of conductive elements into polymers improves electrical signal transmission, influencing cellular behavior positively. Innovations include advanced 3D-printed poly (l-lactic acid) scaffolds, polyurethane foam scaffolds promoting cell differentiation, and responsive polymeric biomaterials for osteogenic and antibacterial drug delivery. Other developments focus on enzyme-responsive and redox-responsive polymers, which offer potential for bone regeneration and combat infection. Biomaterials responsive to mechanical, magnetic, and acoustic stimuli also show potential in bone regeneration, including mechanically-responsive polymers, magnetic-responsive biomaterials with superparamagnetic iron oxide nanoparticles, and acoustic-responsive biomaterials. In conclusion, smart biopolymers are reshaping scaffold design and bone regeneration strategies. However, understanding their advantages and limitations is vital, indicating the need for continued exploratory research.

Smart superplasticizers based on redox-responsive polymers for rheology control of cementitious materials

A new concept is introduced for active rheology control of cementitious materials using stimuli-responsive polymers. RAFT polymerization of methacrylic acid (MAA) and 2,2,6,6, tetramethyl-4-piperidyl methacrylate (TMPMA) was employed to prepare poly(MAA-co-TMPMA) as precursor for the preparation of poly(MAA-co-TEMPO), a redox-responsive copolymer containing 2,2,6,6-tetramethylpiperidine-1-oxyl group. Poly(MAA-co-TEMPO) is soluble in alkaline water and undergoes a redox switch when electrically triggered, oxidizing the TEMPO group to the oxoammonium cations (TEMPO+). The observed active stiffening control is hypothesized to result from adsorption of the negatively charged copolymer with the TEMPO side chains on cement particles and (partial) desorption of the zwitterionic copolymer with the TEMPO+ side chains. The new chemical admixtures could enhance flowability of cement pastes at low W/C ratio and sharply increase storage modulus when applying an electric potential of 1 V. Poly(MAA-co-TEMPO) acts as smart superplasticizer that can actively alter the rheology of cementitious materials upon applying an electric voltage.

Research on preparation and antitumor activity of redox-responsive polymer micelles co-loaded with sorafenib and curcumin

A novel redox-responsive mPEG-SS-PLA (PSP) polymeric micelle was synthesized and prepared for the delivery of sorafenib (SAF) and curcumin (CUR). And a series of validations were conducted to confirm the structure of the synthesized polymer carriers. Using the Chou-Talalay approach, the combination indexes (CI) of SAF and CUR were determined, and explore the inhibitory effects of the two drugs on HepG2R cells at different ratios. SAF/CUR-PSP polymeric micelles were prepared by thin film hydration method, and the physicochemical properties of nanomicelles were evaluated. The biocompatibility, cell uptake, cell migration, and cytotoxicity assays were assessed in HepG2R cells. The expression of the phosphoinositol-3 kinase (PI3K)/serine/threonine kinase (Akt) signaling pathway was detected by Western blot assay. Additionally, the tumor suppressive effect of SAF/CUR-PSP micelles was clearly superior to free drug monotherapy or their physical combination in HepG2 cell-induced tumor xenografts. The current study revealed that mPEG-SS-PLA polymer micelles loaded with SAF and CUR showed the enhanced therapeutic effects against hepatocellular carcinoma in vitro and in vivo models. It has promising applications for cancer therapy.

Controlling Morphologies of Redox-Responsive Polymeric Nanocarriers for a Smart Drug Delivery System.

Redox-responsive nanocarriers using disulfides or thiols have received considerable attention owing to the higher levels of glutathione (GSH) in cancer cells than those in extracellular fluids. Nevertheless, the normal-to-cancer-cell selectivity of these nanocarriers has not yet been clarified. Nanocarriers exhibit different cytotoxicities depending on the morphologies they adopt under the redox-active conditions typically existing in cancerous cells. Therefore, not only GSH levels but also reactive oxygen species (ROS) levels and other complex cancerous cell conditions must be considered for the development of smart drug delivery systems. In this article, we review the structural design of redox-responsive polymers that exhibit different morphological changes in environments akin to cancerous cells (e. g., GSH- and ROS-abundant conditions). In addition, we propose a molecular design for the spatiotemporal control of nanocarrier morphology depending on the levels of both GSH and ROS upon photoirradiation to increase the cytotoxicity difference between normal and cancer cells.

Sponge-like nano-system suppresses tumor recurrence and metastasis by restraining myeloid-derived suppressor cells-mediated immunosuppression and formation of pre-metastatic niche.

Tumor recurrence and metastasis still greatly limit the therapeutic efficiency on the majority of postoperative clinical cases. With the aim to realize more powerful treatment outcomes on postoperative malignant tumors, a sponge-like neutrophil membrane-coated nano-system (NM/PPcDG/D) was fabricated to inhibit tumor recurrence and metastasis by inhibiting the recruitment and functions of myeloid-derived suppressor cell (MDSCs), which reinforced anti-tumor immunity and also suppressed pulmonary metastasis by inhibiting the formation of pre-metastatic niche (PMN). Firstly, PPcDG/D nanoparticles (NPs) were formulated by the self-assembling and crosslinking of synthesized redox-responsive polymer (PPDG) with doxorubicin (DOX) loading in the nanocore (PPcDG/D), followed by coating with activated neutrophils membrane to fabricate biomimetic NM/PPcDG/D. The sponge-like NM/PPcDG/D not only showed obvious natural tropism to postoperative inflammatory site, but also inhibited the recruitment and functions of MDSCs, thus relieved MDSCs-mediated immunosuppression. Additionally, NM/PPcDG/D also suppressed the formation of PMN to inhibit pulmonary metastasis by reducing the recruitment of MDSCs, decreasing the permeability of pulmonary vessels and inhibiting the implantation of circulating tumor cell (CTCs). Eventually, this fabricated NM/PPcDG/D NPs significantly inhibited tumor recurrence and metastasis on postoperative triple negative breast cancer (TNBC) model, presenting a promising therapeutic strategy on postoperative malignant tumors. STATEMENT OF SIGNIFICANCE: Myeloid-derived suppressor cells (MDSCs) play important roles in accelerating tumor recurrence and metastasis by promoting the establishment of immunosuppression in postoperative inflammatory regions and facilitating the formation of pulmonary pre-metastasis niche (PMN). In order to achieve enhanced suppression of recurrence and metastasis, a sponge-like NM/PPcDG/D nano-system was designed and fabricated. This nano-system is also the first attempt to integrate the regulation effects of a nano-sponge and anti-inflammatory agent to achieve enhanced multi-mode manipulation of MDSCs. Ultimately, NM/PPcDG/D powerfully restrained the recurrence and spontaneous metastasis on TNBC model. This article also revealed the particular roles of MDSCs involved in the regulation networks of postoperative recurrence and metastasis, immunosuppression and inflammation.

Smart Polymeric Nanoparticles in Cancer Immunotherapy.

Cancer develops with unexpected mutations and causes death in many patients. Among the different cancer treatment strategies, immunotherapy is promising with the benefits of high specificity and accuracy, as well as modulating immune responses. Nanomaterials can be used to formulate drug delivery carriers for targeted cancer therapy. Polymeric nanoparticles used in the clinic are biocompatible and have excellent stability. They have the potential to improve therapeutic effects while significantly reducing off-target toxicity. This review classifies smart drug delivery systems based on their components. Synthetic smart polymers used in the pharmaceutical industry, including enzyme-responsive, pH-responsive, and redox-responsive polymers, are discussed. Natural polymers derived from plants, animals, microbes, and marine organisms can also be used to construct stimuli-responsive delivery systems with excellent biocompatibility, low toxicity, and biodegradability. The applications of smart or stimuli-responsive polymers in cancer immunotherapies are discussed in this systemic review. We summarize different delivery strategies and mechanisms that can be used in cancer immunotherapy and give examples of each case.

Thioether-based poly(2-oxazoline)s: from optimized synthesis to advanced ROS-responsive nanomaterials

Intelligent redox-responsive polymers, such as thioether-containing poly(2-oxazoline)s, facilitate drug delivery and triggered release in biomedical applications.

Redox-Responsive Polymer Nanoreactors Based on Methionine Sulfoxide for Monitoring Cell Adhesion.

Expanding the category of redox-responsive monomers suitable for enzymolysis efficiency regulation and application to living biosystems is a prerequisite to complementing the fabrication of stimuli-responsive polymer nanoreactors. However, the development of redox-responsive monomers is severely limited by chemical oxidation and low biocompatibility. This work presents a protocol for overcoming this problem by the self-assembly of redox-responsive polymer nanoreactors containing segments of water-soluble methionine sulfoxide residues and poly(styrene-co-maleic anhydride-l-methionine), and by immobilizing α-l-fucosidase into the nanoreactors. These nanoreactors demonstrate highly selective responses to a mild redox triggered by H2O2 from the initial state (VO) to an oxidation state (VO1), and are reduced by methionine sulfoxide reductase A to mold the VO' state. It resulted in significantly enhanced enzymolysis efficiency and maximal reaction rates 8.1-fold (VO) and 23.3-fold (VO1) higher than those of the free enzyme. Moreover, cell adhesion was evaluated by the highly selective determination of l-fucose on cell surfaces. Using a combination of chemical oxidation and enzymatic reduction, this work achieves reiterative enzymolysis efficiency regulation of polymer nanoreactors, which has great potential for the construction of redox-responsive nanoreactors and for monitoring cell adhesion.

Synthesis of a targeted, dual pH and redox-responsive nanoscale coordination polymer theranostic against metastatic breast cancer in vitro and in vivo

Background Nanoscale coordination polymers (nCP) have exhibited a great potential in designing of the theranostic platforms in the latest years. However, they have low selectivity for cancerous tissues and require to be modified for becoming effective cancer therapeutics. In this study, a novel nanoscale pH and redox-responsive coordination polymer with high selectivity was synthesized. Methods The nCP was synthesized by iron(III) chloride and dithiodiglycolic acid. After loading the prepared nCP with doxorubicin (DOX), nCP was coated with an amphiphilic copolymer composed of α-tocopheryl succinate-polyethylene glycol (VEP). Next, AS1411 aptamer was decorated on the VEP shell of the DOX-loaded nCP (Apt-VEP-nCP@DOX) to provide a guided drug delivery platform. Results The prepared platform demonstrated high DOX loading capacity and pH and redox-responsive DOX release. Apt-VEP-nCP@DOX displayed greater DOX internalization and toxicity towards breast cancer cells of 4T1 and MCF7 compared with that of non-targeted VEP-nCP@DOX. Also, the intravenous injection of Apt-VEP-nCP@DOX (a single dose) considerably suppressed the 4T1 tumor growth in vivo. Moreover, Apt-VEP-nCP@DOX showed outstanding magnetic resonance (MR) imaging capability for 4T1 adenocarcinoma diagnosis in ectopic 4T1 tumor model in mice. Conclusions The developed innovative intelligent Apt-VEP-nCP@DOX could serve as a safe and biocompatible theranostic platform appropriate for further translational purposes against breast cancer.

Benzothiazole-disulfide based redox-responsive polymers: facile access to reversibly functionalizable polymeric coatings

Redox-responsive polymers and polymeric coatings containing benzothiazole-disulfide groups provide facile access to reversibly functionalizable platforms.

Fluorinated Ferrocene Moieties as a Platform for Redox-Responsive Polymer 19F MRI Theranostics

Fluorinated Ferrocene Moieties as a Platform for Redox-Responsive Polymer ¹⁹F MRI Theranostics

A Redox-Responsive Nanovaccine Combined with A2A Receptor Antagonist for Cancer Immunotherapy.

In situ vaccination can trigger an antitumor immune response. However, the therapeutic effect is still limited since the high expression of adenosine binding to G protein-coupled receptor A2AR induces an immunosuppressive effect. In this work, a new formulation is presented with the combination of a nanovaccine based on redox-responsive polymer micelles and A2AR antagonist SCH58261. The micelles simultaneously encapsulate immunogenic cell death (ICD) inducer doxorubicin (DOX) and adjuvant toll-like receptor 7 and 8 (TLR7/8) agonist R848, acting as the potent in situ vaccines. A high concentration of glutathione in tumor cells leads to the disintegration of these micelles, releasing DOX and R848 to mediate ICD, inducing the activation of dendritic cells and initiating an immune response. Meanwhile, A2AR antagonist SCH58261, a generation immune checkpoint blocker, inhibits the immunosuppressive adenosinergic pathway in the tumor microenvironment, activating natural killer (NK) cells and CD8+ T cells, and inhibiting the proliferation of regulatory T cells. Therefore, this formulation can trigger a robust systemic antitumor immune response.

Redox Responsive Copolyoxalate Smart Polymers for Inflammation and Other Aging-Associated Diseases.

Polyoxalate (POx) and copolyoxalate (CPOx) smart polymers are topics of interest the field of inflammation. This is due to their drug delivery ability and their potential to target reactive oxygen species (ROS) and to accommodate small molecules such as curcumin, vanilline, and p-Hydroxybenzyl alcohol. Their biocompatibility, ultra-size tunable characteristics and bioimaging features are remarkable. In this review we discuss the genesis and concept of oxylate smart polymer-based particles and a few innovative systemic delivery methods that is designed to counteract the inflammation and other aging-associated diseases (AADs). First, we introduce the ROS and its role in human physiology. Second, we discuss the polymers and methods of incorporating small molecule in oxalate backbone and its drug delivery application. Finally, we revealed some novel proof of concepts which were proven effective in disease models and discussed the challenges of oxylate polymers.

Efficient construction of a redox responsive thin polymer layer on glassy carbon and gold surfaces for voltage-gated delivery applications

The notoriously non-selective aryl-diazonium surface-functionnalization turned selective in the presence of the electron-deficient heterocycle. The electro-activation of the probe allowed the rapid and nearly quantitative liberation of covalently tethered ligands.