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1.
Biomed Pharmacother ; 174: 116482, 2024 May.
Article in English | MEDLINE | ID: mdl-38520866

ABSTRACT

Chemoimmunotherapy has emerged as a promising strategy for improving the efficacy of cancer treatment. Herein, we present PD-1 receptor-presenting membrane-coated paclitaxel dimers nanoparticles (PD-1@PTX2 NPs) for enhanced treatment efficacy. PD-1 cell membrane-cloaked PTX dimer exhibited effective cellular uptake and increased cytotoxicity against cancer cells. PD-1@PTX2 NPs could selectively bind with PD-L1 ligands expressed on breast cancer cells. Our nanoparticles exhibit a remarkable tumor growth inhibition rate of 71.3% in mice bearing 4T1 xenografts and significantly prolong survival in mouse models of breast cancer. Additionally, our nanoparticles promoted a significant 3.2-fold increase in CD8+ T cell infiltration and 73.7% regulatory T cell (Treg) depletion within tumors, boosting a robust antitumor immune response. These findings underscore the potential of utilizing immune checkpoint receptor-presented PTX nanoparticles to enhance the efficacy of chemoimmunotherapy, providing an alternative approach for improving cancer treatment.


Subject(s)
Immunotherapy , Mice, Inbred BALB C , Nanoparticles , Paclitaxel , Programmed Cell Death 1 Receptor , Paclitaxel/pharmacology , Paclitaxel/administration & dosage , Animals , Nanoparticles/chemistry , Programmed Cell Death 1 Receptor/metabolism , Female , Humans , Immunotherapy/methods , Mice , Cell Line, Tumor , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/immunology , Cell Membrane/metabolism , Cell Membrane/drug effects , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/administration & dosage , Xenograft Model Antitumor Assays , Dimerization , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , B7-H1 Antigen/metabolism
2.
Front Pharmacol ; 15: 1345522, 2024.
Article in English | MEDLINE | ID: mdl-38510646

ABSTRACT

Cancer cells have adapted to rapid tumor growth and evade immune attack by reprogramming their metabolic pathways. Glutamine is an important nitrogen resource for synthesizing amino acids and nucleotides and an important carbon source in the tricarboxylic acid (TCA) cycle and lipid biosynthesis pathway. In this review, we summarize the significant role of glutamine metabolism in tumor development and highlight the vulnerabilities of targeting glutamine metabolism for effective therapy. In particular, we review the reported drugs targeting glutaminase and glutamine uptake for efficient cancer treatment. Moreover, we discuss the current clinical test about targeting glutamine metabolism and the prospective direction of drug development.

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