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.

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.

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.

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).

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.