Checkpoint blockade immunotherapy is promising for clinical treatment of various malignant tumors. However, checkpoint blockade immunotherapy suffers from a low response rate due to insufficient tumor immunogenicity and the immunosuppressive tumor microenvironment (ITM). In this study, a tumor-microenvironment-activatable binary cooperative prodrug nanoparticle (BCPN) is rationally designed to improve immunotherapy by synergistically modulating the immune tumor microenvironment. BCPN is purely constructed from a tumor acidity and reduction dual-responsive oxaliplatin (OXA) prodrug for triggering immunogenic cell death (ICD) and eliciting antitumor immunity, and a reduction-activatable homodimer of NLG919 for inactivating indoleamine 2,3-dioxygenase 1, which is a key regulator for ITM. Upon tumor-acidity-triggered cleavage of the poly(ethylene glycol) shell, PN shows negative to positive charge switch for enhanced tumor accumulation and deep penetration. OXA and NLG919 are then activated in the tumor cells via glutathione-mediated reduction. It is demonstrate that activated OXA promotes intratumoral accumulation of cytotoxic T lymphocytes by triggering ICD of cancer cells. Meanwhile, NLG919 downregulates IDO-1-mediated immunosuppression and suppresses regulatory T cells. Most importantly, PN shows much higher efficiency than free OXA or the combination of free OXA and NLG919 to regress tumor growth and prevent metastasis of mouse models of both breast and colorectal cancer.
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http://dx.doi.org/10.1002/adma.201803001 | DOI Listing |
Anticancer Agents Med Chem
January 2025
Cancer Center, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China.
Dysregulated lipid metabolism within the tumor microenvironment (TME) is a critical hallmark of cancer progression, with lipids serving as a major energy source for tumor cells. Beyond their role in cell membrane synthesis, lipids also provide essential substrates for biomolecule production and activate signaling pathways that regulate various cellular processes. Aberrant lipid metabolism impacts not only function but also alters the behavior of immune and stromal cells within the TME.
View Article and Find Full Text PDFCurr Pharm Des
January 2025
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, Hubei, China.
Background: The Prickle2 (Pk2) gene shows promising potential in uncovering the underlying causes of epilepsy, a neurological disorder that is currently not well understood. This paper utilizes the online tool PubMed to gather and condense information on the involvement of PCP channels and the associated roles of PCP pathway molecules in the onset of epilepsy. These findings are significant for advancing epilepsy treatment.
View Article and Find Full Text PDFCancer Commun (Lond)
January 2025
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
Discov Oncol
January 2025
Department of Clinical Laboratory, Affiliated Hospital of Guangdong Medical University, No. 57 South Renmin Avenue, Xiashan District, Zhanjiang, 524001, People's Republic of China.
Objective: Circulating protein level ratios (CPLRs) may play a crucial role in tumor progression and drug resistance by mediating interactions within the tumor microenvironment. This study aims to investigate the causal associations between CPLRs and papillary thyroid cancer (PTC), focusing on their potential implications in drug resistance mechanisms.
Methods: Genetic data for 2821 CPLRs were obtained from the GWAS and FinnGen databases.
Biochem Genet
January 2025
Anhui Province Key Laboratory of Basic Research and Transformation of Age-Related Diseases, Wannan Medical College, Wuhu, 241002, Anhui, P. R. China.
The metabolic pathway of aerobic glycolysis in tumor cells has garnered significant attention in tumor research because of its high activation in cancer cells. Previous research conducted by our team has demonstrated that Apolipoprotein M (APOM) exhibits potential as a factor against liver cancer. However, further investigations are needed to elucidate the precise approach and mechanism that are involved in this process.
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