cenderitide (CD-NP) / Capricor - LARVOL DELTA

Beyond biomarkers: designer natriuretic peptides and cGMP centered therapies for cardiorenal and cardiometabolic protection in chronic heart failure. (PubMed, Intern Emerg Med) - "Recent advances in peptide engineering have enabled the development of novel designer NPs, including Cenderitide, aimed at restoring and enhancing their signalling...Additional engineered peptides, including ANX042, MANP, and CRRL269, as well as complementary approaches targeting the cGMP pathway, such as soluble guanylate cyclase (sGC) stimulators, neprilysin inhibitors, and GC-A positive allosteric modulators, are further expanding the therapeutic potential of NP-centred therapies. Beyond cardiovascular effects, NPs also influence metabolic regulation and renal function, highlighting their relevance in cardiometabolic disease. Collectively, these developments support a shift from the use of NPs solely as biomarkers toward their emerging role as therapeutic targets and agents in the treatment of CHF."

Biomarker • Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders

Molecular Mechanisms of Effects of Lead and Cadmium Co-exposure on Atrial and Ventricular Myocardium: Soluble Salts Versus Nanoparticles. (PubMed, Cardiovasc Toxicol) - "In the PbNP+CdNP group, myosin kinetics was reduced in all heart chambers, and the MHC ratio shifted toward the β-isoform in the ventricles. The effects of co-exposure to Pb and Cd differ from those of isolated exposures and depend on the chemical forms of the toxicants and the specific heart chamber."

Journal • Cardiovascular

Structural and Biochemical Insights into the Arabinose and Xylose Derivatives of Cyclic-GAMP-Mediated Inhibition of Mycobacterium tuberculosis Cyclic-di-AMP Phosphodiesterase. (PubMed, Biochemistry) - "The cocrystal structure demonstrates that the arabinose-derived 2'3'-cGAMP (AR-cGAMP) analogue is trapped in an unusual U-shaped conformation in the substrate-binding pocket, away from the catalytic residue and Mn2+, which suggests that CdnP is incompetent to hydrolyze the analogue and cannot accept the other CDN substrate for hydrolysis. Given that several bacterial and viral pathogens deploy CDN phosphodiesterase enzymes to hydrolyze both host and pathogen-derived STING agonists, sugar-modified CDNs can be used to weaken bacterial and viral defenses and stimulate the STING-mediated host immunity against these pathogens."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CGAS • ENPP1

Pharmacological polarization of tumor-associated macrophages toward a CXCL9 antitumor phenotype (CIMT 2026) - "The platform was evaluated in tumor-bearing mice, where biodistribution and cellular targeting were quantified by flow cytometry, and intravital window-chamber imaging assessed CDNP accumulation and CXCL9Hi induction in TAM populations across two tumor models...Screening identified R848 (TLR7/8 agonist), MSA-2 (STING agonist), and RBN2397 (PARP7 inhibitor) as the most potent inducers, increasing CXCL9 expression ~8-fold compared with Interferon-γ control...Tumor growth experiments showed complete remission lasting 60 days without significant weight loss, whereas free drug administration caused pronounced toxicity. These data demonstrate that CDNPs enable systemic, selective delivery of immunomodulators to TAMs and support strong induction of a CXCL9Hi phenotype, resulting in tumor control with favourable tolerability."

IO biomarker • Brain Cancer • Glioma • Oncology • Solid Tumor • CXCL10 • CXCL9 • IFNG • IL12A • TIPARP

Combined antiretroviral therapy with low- or normal-protein, high-calorie diets appears to induce significant deleterious electrocardiographic changes in a rodent model. (PubMed, Braz J Med Biol Res) - "Each dietary group was then subdivided into four treatment groups for a further 9 weeks: a standard group (normal saline), Test group 1 (dolutegravir (DTG) plus tesamorelin), Test group 2 (DTG only), and a positive control (classical cART regimen)...Significant intergroup variations in ECG indices were observed, including Q, R, S, and T wave amplitudes, PR interval, QRS duration, ST height, and QTc (all P<0.0001)...These findings demonstrated that CDLP and CDNP diets, combined with DTG-based or classical cART regimens, exerted deleterious cardiac effects, promoting myocardial fibrosis that disrupts normal electrical conduction and may predispose to arrhythmogenesis. Tesamorelin prevented these effects, implicating growth hormone pathway dysfunction in the underlying pathology."

Journal • Preclinical • Cardiovascular • Fibrosis • Human Immunodeficiency Virus • Immunology • Infectious Disease

Structural and biochemical insights into the inhibition of Mycobacterium tuberculosis cyclic dinucleotide phosphodiesterase by a sulfur-modified cyclic dinucleotide analog. (PubMed, RSC Chem Biol) - "Additionally, 2'3'-cGAMP in the STING receptor and ES-2'3'-cAAMP in the CdnP adopted an identical horseshoe conformation, suggesting that ES-2'3'-cAAMP, or an analogue thereof, can bind to and stimulate STING, thus acting as a synthetic STING agonist. These combined structural and biochemical findings provide new mechanistic insights into the inhibition of Mtb CdnP and offer a novel approach to host-directed anti-TB therapies that aim to enhance the host's own immune responses rather than directly killing the pathogen, which may help to mitigate the problem of antibiotic resistance."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Cell-derived Nanoparticles Provide a Robust Platform to Manufacture Therapeutic T cells. (PubMed, Res Sq) - P1 | "CDNPs robustly expanded T cells from patients whose products could not be manufactured using standard approaches, and these CDNP-derived CAR T cells controlled tumors in humanized mouse models. In a phase I trial of patients with CD19⁺ malignancies (NCT04684563), cGMP-compatible CDNPs enabled streamlined 3-day manufacturing of IL-18-expressing CD19 CAR T cells, yielding higher cell recovery and durable clinical responses without unexpected toxicities, supporting CDNPs as a platform for commercial CAR T cell production."

Journal • Oncology • CD19 • CD86 • IL15 • IL18 • IL7

Multimodality mapping of immunotherapy distribution as a predictive marker in glioma. (PubMed, Neuro Oncol) - "We develop a customizable imaging platform to map drug delivery to glioma with broad applicability in neuroscience and neurooncology."

Biomarker • IO biomarker • Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • CD8 • IL12A • IL13 • MGMT

Multimodality mapping of immunotherapy distribution as a prognostic marker in glioma (SNO 2025) - "We find that in contrast to the susceptible Gl261 glioma model, SB28 gliomas are characterized by poor immunogenicity due to low MHC expression and resistance to Toll-like receptor (TLR) 7 targeted therapy by CDNP-R848 nanoparticles...In a translational analysis of the multicenter N2M2/NOA20 trial we validate that edema and microvascular pathology are also associated with poor prognosis in glioblastoma patients treated with anti-PD-L1 immunotherapy and that patients without edema have increased progression free survival (PFS). In summary, we develop a customizable imaging platform (3D-MR-LSM) to three-dimensionally map drug delivery to the central nervous system (CNS) with broad applicability in neuroscience and oncology."

Biomarker • IO biomarker • Brain Cancer • Glioblastoma • Glioma • Solid Tumor • CD8 • IL12A • IL13

Assessing the immune microenvironment in glioma models by correlative high field MRI and light sheet microscopy (SNO 2025) - "To induce a proinflammatory shift in the TME, we used the Toll-like receptor 7 agonist CDNP-R848, which effectively treated preclinical Gl261 glioma...TME complexity appeared to develop prior to therapy. These findings indicate that the recruitment pathways of myeloid and T cells are crucial for understanding potential resistance to glioma immunotherapy."

Brain Cancer • Glioma • Solid Tumor

Advanced imaging, immune profiling and nanoparticle immunotherapy distribution in H3K27M-mutated Diffuse Midline Glioma models: identifying and translating MRI signatures (SNO 2025) - "Additionally, we assessed the biodistribution of fluorescently labeled cyclodextrin (CDNP)-nanoparticle therapy upon intravenous administration in the tumor microenvironment by light sheet microscopy. MRI data indicate unique imaging signatures associated with different primary tumor locations. We found strong infiltration along white matter tracts and distinct immune profiles. SE-DTI tractography was utilized to reconstruct white matter tracts to further identify DMG infiltration pathways."

IO biomarker • Metastases • Brain Cancer • Diffuse Midline Glioma • Glioma • Solid Tumor

Assessing the immune microenvironment in glioma models by correlative high field MRI and light sheet microscopy (WFNOS 2025) - "To induce a proinflammatory shift in the TME, we used the Toll-like receptor 7 agonist CDNP-R848, which effectively treated preclinical Gl261 glioma...TME complexity appeared to develop prior to therapy. These findings indicate that the recruitment pathways of myeloid and T cells are crucial for understanding potential resistance to glioma immunotherapy."

Brain Cancer • Glioma • Oncology • Solid Tumor

Advanced imaging, immune profiling and nanoparticle immunotherapy distribution in H3K27M-mutated Diffuse Midline Glioma models:  identifying and translating MRI signatures (WFNOS 2025) - "Additionally, we assessed the biodistribution of fluorescently labeled cyclodextrin (CDNP)-nanoparticle therapy upon intravenous administration in the tumor microenvironment by light sheet microscopy. MRI data indicate unique imaging signatures associated with different primary tumor locations. We found strong infiltration along white matter tracts and distinct immune profiles. SE-DTI tractography was utilized to reconstruct white matter tracts to further identify DMG infiltration pathways."

IO biomarker • Metastases • Brain Cancer • Diffuse Midline Glioma • Glioma • Solid Tumor

Multimodality mapping of immunotherapy distribution as a prognostic marker in glioma (WFNOS 2025) - "We find that in contrast to the susceptible Gl261 glioma model, SB28 gliomas are characterized by poor immunogenicity due to low MHC expression and resistance to Toll-like receptor (TLR) 7 targeted therapy by CDNP-R848 nanoparticles...In a translational analysis of the multicenter N2M2/NOA20 trial we validate that edema and microvascular pathology are also associated with poor prognosis in glioblastoma patients treated with anti-PD-L1 immunotherapy and that patients without edema have increased progression free survival (PFS). In summary, we develop a customizable imaging platform (3D-MR-LSM) to three-dimensionally map drug delivery to the central nervous system (CNS) with broad applicability in neuroscience and oncology."

Biomarker • IO biomarker • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • CD8 • IL12A • IL13

Metformin attenuates coal dust nanoparticle-induced pulmonary fibrosis by modulating inflammation and epithelial-mesenchymal transition. (PubMed, Int Immunopharmacol) - "Coal worker pneumoconiosis is an occupational pulmonary fibrosis (PF) caused by prolonged exposure to respirable coal dust (CD), with limited therapeutic options. These findings indicate that Met attenuates CD-NP-induced PF by inhibiting oxidative stress, inflammation, and EMT, potentially by targeting IGF1/IGF1R, AKT/GSK3β, and NF-κB/NLRP3 signaling. Its preventive efficacy highlights promising translational value for occupational PF intervention."

Journal • Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IGF1 • NLRP3

Molecular Basis of Cadmium Cardiotoxicity: Chamber-Specific Effects of CdO Nanoparticles and Soluble CdCl2 Exposure. (PubMed, Food Chem Toxicol) - "Thus, exposure to CdNP could exhibit greater cardiotoxicity than CdCl2, with opposite effects on the right ventricle. Therefore, molecular mechanisms of cadmium's influence on specific heart chambers should be considered when developing strategies for heart disease management."

Journal • Cardiovascular • Heart Failure

Discovery of natural CdnP inhibitors through structure-based virtual screening and molecular dynamics simulations. (PubMed, Microbiol Spectr) - "Furthermore, the detailed structural insights and inhibitory mechanisms elucidated through molecular dynamics simulations provide valuable knowledge for rational drug design. This research bridges natural product discovery with computational biology to address the urgent need for novel TB treatments, especially against drug-resistant strains, presenting a significant advancement toward more effective therapeutic interventions for this persistent global health threat."

Journal • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • STING

Review on the utilization of metal organic frameworks (MOFs) for eliminating ibuprofen and naproxen from water sources. (PubMed, Environ Sci Pollut Res Int) - "This study demonstrated that MOFs, including Pd@MIL-100(Fe), UiO-67@β-CD-NP, HSO₃-MIL-53(Fe), and UiO-66-MOF, are capable of achieving complete removal of the targeted pharmaceuticals. This review concludes that MOFs, particularly those following the Langmuir adsorption isotherm model and PSO adsorption kinetics, are promising for the effective removal of IBU and NPX. These results highlight the potential of MOFs in addressing pharmaceutical contamination and suggest further research, particularly in optimizing MOF structures for environmental applications."

Journal • Review

Cyclodextrin Nanoparticles and Injectable Polymer-Nanoparticle Hydrogels for Macrophage-Targeted Delivery of Small-Molecule Drugs. (PubMed, Methods Mol Biol) - "We have, therefore, developed a macrophage-targeted nanoparticulate carrier (cyclodextrin nanoparticle [CDNP]) that can house a variety of hydrophobic small-molecule drugs for systemic delivery through the body. This system has further been manipulated to formulate an injectable polymer-nanoparticle (iPNP) hydrogel for local delivery, with the goal of concentrating drug effects at the target site while perpetuating sustained delivery and minimizing off-target effects. Herein, we describe the strategy for preparing these CDNPs and iPNP hydrogels for a wide range of therapeutic applications."

Journal • Immune Modulation • Immunology • Oncology

Enhanced bioaccessibility of cyclolinopeptides via zein-cyclodextrin nanoparticles: Simulated gastrointestinal digestion and cellular uptake study. (PubMed, Food Chem) - "Z-CD NP had a smaller diameter (Dh) and better encapsulation effect on CLS...Z-CD NPs also enhanced absorption and reduced secretion of CLS after digestion. Overall, this study provides a simple approach to enhance the oral delivery efficiency of CLS by modulating Z-based NPs with CD."

Journal • Gastrointestinal Disorder

Targeted Analysis of Mitochondrial Protein Conformations and Interactions by Endogenous ROS-Triggered Cross-Linker Release. (PubMed, Adv Sci (Weinh)) - "1718 intra-links reveal dynamic conformations involving chaperones with ATP-dependent conformation cycles, and 385 inter-links reveal dynamic interactions involving OXPHOS complexes and 27 pairs of possible potential interactions. These results signify that R-CDNP can achieve dynamic conformation and interaction analysis of mitochondrial proteins in living cells, thereby contributing to a better understanding of their biological functions."

Journal

Metal Ion-Condensed DNA Nanoparticle Library: Phase Separation and Transition and Antisense Therapy Applications. (PubMed, ACS Appl Mater Interfaces) - "In addition, the Mn+-controlled anticancer therapeutic efficiency of the Mn+-CDNP library as a state-of-the-art gene delivery platform was demonstrated even for unmodified antisense oligonucleotides in association with the potential toxicity of the Mn+s released from the Mn+-CDNPs. This comprehensive study of the Mn+-dependent condensation of nucleic acids provides profound insights into the chemistry of the nucleic acid-Mn+ interactions and the reliable theragnostic applications of Mn+-CDNPs as functional nucleic acid nanostructures."

Journal • Gene Therapies • Oncology

Macrophage-targeted drug delivery for systemic and local immunotherapy (ACS-Fall 2024) - "Hydrogels released CDNP-celastrol for >14 days with >80% inhibition of inflammatory response (Fig 1C). In sum, small-molecules can potently modulate MF-state and their efficacy is improved through cell- and tissue-targeted delivery to aid clinical translation."

Oncology

Interfacial engineering method to regulate the performances of bilayer emulsions co-stabilized by casein/butyrylated dextrin nanoparticles and chitosan. (PubMed, Int J Biol Macromol) - "In present study, bilayer emulsions with different interfacial structures stabilized by casein/butyrylated dextrin nanoparticles (CDNP), chitosan (CS) and chitosan nanoparticles (CSNP) were prepared to overcome the limitations of conventional emulsions...This study also provides a new material for the preparation of delivery systems that protect biologically active compounds. Bilayer emulsions are promising for applications in traditional and manufactured food products."

Journal

Sex-stratified genome-wide association and transcriptome-wide Mendelian randomization studies reveal drug targets of heart failure. (PubMed, Cell Rep Med) - "Three drug target genes show sex-differential effects on HF/HFrEF via influencing LVEF, with NPR2 as the target gene for the HF drug Cenderitide under phase 2 clinical trial. Our study highlights the importance of considering sex-differential genetic effects in sex-balanced diseases such as HF and emphasizes the value of sex-stratified GWASs and MR in identifying putative genetic variants, causal genes, and candidate drug targets for HF, which is not identifiable using a sex-combined strategy."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure