Chimeric Peptide Functionalized Immunostimulant to Orchestrate Photodynamic Immunotherapeutic Effect by PD-L1 Deglycosylation and CD47 Inhibition.

Breast cancer utilizes diverse immunosuppressive mechanisms to evade immune surveillance, thereby impairing immunotherapeutic effects. In this work, a chimeric peptide functionalized immunostimulant (designated as aGlyR) is fabricated to boost photodynamic immunotherapy through PD-L1 deglycosylation and CD47 inhibition. The photosensitizer protoporphyrin IX (PpIX) is conjugated to a PD-L1 deglycosylation peptide via a hydrophilic PEG linker, yielding the chimeric peptide Fmoc-K(PpIX)-PEG-GFTATPPAPDSPQEP.

Chimeric Peptide-Engineered Polyprodrug Enhances Cytotoxic T Cell Response by Inducing Immunogenic Cell Death and Upregulating Major Histocompatibility Complex Class I.

Tumor-specific cytotoxic T cell immunity is critically dependent on effective antigen presentation and sustained signal transduction. However, this immune response is frequently compromised by the inherently low immunogenicity of breast cancer and the deficiency in major histocompatibility complex class I (MHC-I) expression. Herein, a chimeric peptide-engineered stoichiometric polyprodrug (PDPP) is fabricated to potentiate the cytotoxic T cell response, characterized by a high drug loading capacity and precise stoichiometric drug ratio, of which the immunogenic cell death (ICD) inducer of protoporphyrin IX (PpIX) and the epigenetic drug of decitabine (DAC) are condensed into a polyprodrug called PpIX-DAC.

Transferrin receptor-targeted immunostimulant for photodynamic immunotherapy against metastatic tumors through -catenin/CREB interruption.

The immunosuppressive phenotype of tumor cells extensively attenuates the immune activation effects of traditional treatments. In this work, a transferrin receptor (TfR) targeted immunostimulant (PTI) is fabricated for photodynamic immunotherapy against metastatic tumors by interrupting -catenin signal pathway. To synthesize PTI, the photosensitizer conjugated TfR targeting peptide moiety (Palmitic-K(PpIX)-HAIYPRH) is unitized to encapsulate the transcription interrupter of ICG-001.

Self-Assembled PD-L1 Downregulator to Boost Photodynamic Activated Tumor Immunotherapy Through CDK5 Inhibition.

The immunosuppressive characteristics and acquired immune resistance can restrain the therapy-initiated anti-tumor immunity. In this work, an antibody free programmed death receptor ligand 1 (PD-L1) downregulator (designated as CeSe) is fabricated to boost photodynamic activated immunotherapy through cyclin-dependent kinase 5 (CDK5) inhibition. Among which, FDA approved photosensitizer of chlorin e6 (Ce6) and preclinical available CDK5 inhibitor of seliciclib (Se) are utilized to prepare the nanomedicine of CeSe through self-assembly technique without drug excipient.

Optical controlled and nuclear targeted CECR2 competitor to downregulate CSF-1 for metastatic breast cancer immunotherapy.

The crosstalk between breast cancer cells and tumor associated macrophages (TAMs) greatly contributes to tumor progression and immunosuppression. In this work, cat eye syndrome chromosome region candidate 2 (CECR2) is identified to overexpress in breast cancer patients, which can recognize v-rel avian reticuloendotheliosis viral oncogene homolog A (RelA) and activate nuclear factor κB (NF-κB) to release colony stimulating factor-1 (CSF-1). Pharmacological inhibition of CECR2 by the bromodomain competitor (Bromosporine, Bro) can downregulate CSF-1 to inhibit M2 type TAMs.

Tumor Homing Chimeric Peptide Rhomboids to Improve Photodynamic Performance by Inhibiting Therapy-Upregulated Cyclooxygenase-2.

Negative therapeutic feedback of inflammation would extensively attenuate the antitumor effect of photodynamic therapy (PDT). In this work, tumor homing chimeric peptide rhomboids (designated as NP-Mel) are fabricated to improve photodynamic performance by inhibiting PDT-upregulated cyclooxygenase-2 (COX-2). The hydrophobic photosensitizer of protoporphyrin IX (PpIX) and palmitic acid are conjugated onto the neuropilin receptors (NRPs) targeting peptide motif (CGNKRTR) to obtain tumor homing chimeric peptide (Palmitic-K(PpIX)CGNKRTR), which can encapsulate the COX-2 inhibitor of meloxicam.

Chimeric Peptide-Engineered Self-Delivery Nanomedicine for Photodynamic-Triggered Breast Cancer Immunotherapy by Macrophage Polarization.

A systemic treatment strategy is urgently demanded to suppress the rapid growth and easy metastasis characteristics of breast cancer. In this work, a chimeric peptide-engineered self-delivery nanomedicine (designated as ChiP-CeR) for photodynamic-triggered breast cancer immunotherapy by macrophage polarization. Among these, ChiP-CeR is composed of the photosensitizer of chlorine e6 (Ce6) and the TLR7/8 agonist of lmiquimod (R837), which is further modified with tumor matrix targeting peptide (Fmoc-K(Fmoc)-PEG-CREKA.

Identification of PHACTR4 as A New Biomarker for Diabetic Nephropathy and Its Correlation with Glomerular Endothelial Dysfunction and Immune Infiltration.

Introduction: The pathophysiology of diabetic nephropathy (DN) is fundamentally dependent on glomerular endothelial cells (GECs), which are a crucial portion of the glomerular filtration barrier. This study aimed to identify biomarker candidates associated with GECs dysfunction in DN by combining microarray and single-cell sequencing dataset analysis.

Methods: Microarray dataset GSE30528 was downloaded from the Gene expression omnibus (GEO) database.

Glycolytic enzyme PFKFB3 regulates sphingosine 1-phosphate receptor 1 in proangiogenic glomerular endothelial cells under diabetic condition.

Glomerular angiogenesis is a characteristic feature of diabetic nephropathy (DN). Enhanced glycolysis plays a crucial role in angiogenesis. The present study was designed to investigate the role of glycolysis in glomerular endothelial cells (GECs) in a mouse model of DN.

Chimeric Peptide Engineered Bioregulator for Metastatic Tumor Immunotherapy through Macrophage Polarization and Phagocytosis Restoration.

Tumor-associated macrophages (TAMs) are the most abundant immune cells in solid tumor tissues, which restrict antitumor immunity by releasing tumor-supporting cytokines and attenuating phagocytosis behaviors. In this work, a chimeric peptide engineered bioregulator (ChiP-RS) is constructed for tumor immunotherapy through macrophage polarization and phagocytosis restoration. ChiP-RS is fabricated by utilizing macrophage-targeting chimeric peptide (ChiP) to load Toll-like receptor agonists (R848) and Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 2 (SHP-2) inhibitor (SHP099).

Drug induced mitochondria dysfunction to enhance photodynamic therapy of hypoxic tumors.

As most solid tumors are characterized by a hypoxic microenvironment, enormous efforts have been made to develop strategies to fight hypoxia. This study shows that ivermectin (IVM), an antiparasitic drug, is able to alleviate tumor hypoxia by inhibiting mitochondrial respiration. We explore this to strengthen oxygen-dependent photodynamic therapy (PDT) using chlorin e6 (Ce6) as a photosensitizer.

Plasma Membrane-Targeted Photooxidant for Chemotherapy-Enhanced Lipid Peroxidation.

Although photodynamic therapy (PDT) is a promising antitumor strategy for tumor treatment, the short half-life and the limited diffusion distance of reactive oxygen species (ROS) greatly hamper its antitumor efficacy. Moreover, tumor cells develop antioxidative microenvironments to weaken the oxidative damage caused by PDT. Herein, a plasma membrane-targeted photooxidant (designated as SCPP) is prepared by the self-assembly of a chimeric peptide (Pal-K(PpIX)-R) and sorafenib.

Carrier free nanomedicine for synergistic cancer therapy by initiating apoptosis and paraptosis.

Although photodynamic therapy (PDT) has been well-known as a promising anti-tumor treatment, its limited therapeutic efficiency remains to be a large challenge. In this study, a carrier free nanomedicine (designated as PyroMor) is developed to greatly initiate cell apoptosis and paraptosis for synergistic cancer therapy. Pyropheophorbide-a (Pyro) and morusin (Mor) are capable of self-assembling into PyroMor, which has been testified to have superiority of improved stability, cellular internalization, and biocompatibility.

Self-delivery nanomedicine for vascular disruption-supplemented chemo-photodynamic tumor therapy.

Tumor vascular blockade is a promising strategy for adjuvant cancer treatment. In this work, a self-delivery nanomedicine is developed based on a vascular disruptor and photosensitizer for tumor synergistic therapy. Specifically, this nanomedicine (designated as CeCA) is comprised of combretastatin A4 (CA4) and chlorine e6 (Ce6) by self-assembly technique.

Circadian misalignment promotes vascular smooth muscle cell apoptosis via defective autophagy.

Defective autophagy in vascular smooth muscle cells (VSMCs) in response to oxidative stress can lead to cellular apoptosis and plaque instability. Previous studies have revealed that the circadian clock system is involved in autophagic regulation and plaque progression. However, the mechanism by which circadian rhythmicity influences VSMC autophagy and plaque stability remains unclear.

Major histocompatibility complexes are up-regulated in glomerular endothelial cells via activation of c-Jun N-terminal kinase in 5/6 nephrectomy mice.

Background And Purpose: This study aims to explore the mechanism underlying the up-regulation of major histocompatibility complex (MHC) proteins in glomerular endothelial cells in 5/6 nephrectomy mice.

Experimental Approach: C57/BL6 mice were randomly allocated to sham-operated (2K) and 5/6 nephrectomy (5/6Nx) groups. Mouse splenic lymphocytes, from either syngeneic or allogeneic background, were injected into 5/6Nx mice after total body irradiation.

Bioinformatics analyses on the immune status of renal transplant patients, a systemic research of renal transplantation.

Background: Kidney transplantation is the most effective treatment for end-stage renal disease. Allograft rejections severely affect survivals of allograft kidneys and recipients.

Methods: Using bioinformatics approaches, the present study was designed to investigate immune status in renal transplant recipients.