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Intralesional injection of CpG ODNs complexed with glatiramer acetate mitigates systemic cytokine toxicities and synergistically advances checkpoint blockade efficacy.
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Kinimmune, Inc. St. Louis, 63141, Missouri, USA.
PD-L1/PD-1 checkpoint inhibitors (CPIs) are mainstream agents for cancer immunotherapy, but the prognosis is unsatisfactory in solid tumor patients lacking preexisting T-cell reactivity. Adjunct therapy strategies including the intratumoral administration of immunostimulants aim to address this limitation. CpG oligodeoxynucleotides (ODNs), TLR9 agonists that can potentiate adaptive immunity, have been widely investigated to tackle PD-L1/PD-1 resistance, but clinical success has been hindered by inconsistent efficacy and immune-related toxicities caused by systemic exposure.
View Article and Find Full Text PDFSelf-assembly of Antisense DNA-Camptothecin Amphiphile into Glutathione-Responsive Nanoparticles for Combination Cancer Therapy.
Chemistry
January 2025
Indian Institute of Science Education and Research Thiruvananthapuram, Chemistry, Trivandrum, Trivandrum, Trivandrum, 695551, Trivandrum, INDIA.
Recent years have witnessed the rapid growth of combination therapy for the treatment of cancer. Chemo and antisense DNA therapies are two clinically proven and efficient treatment modalities for cancer. However, direct delivery of both chemo and antisense oligonucleotides into the cancerous cells is challenging and hence there is a high demand for the development of new strategies that permit the direct delivery of chemo and antisense therapeutic agents in a targeted fashion.
View Article and Find Full Text PDFIntelligent Design of Lipid Nanoparticles for Enhanced Gene Therapeutics.
Mol Pharm
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ZJU-Hangzhou Global Scientific and Technological Innovation Canter, Zhejiang University, Hangzhou, Zhejiang 311215, China.
Lipid nanoparticles (LNPs) are an effective delivery system for gene therapeutics. By optimizing their formulation, the physiochemical properties of LNPs can be tailored to improve tissue penetration, cellular uptake, and precise targeting. The application of these targeted delivery strategies within the LNP framework ensures efficient delivery of therapeutic agents to specific organs or cell types, thereby maximizing therapeutic efficacy.
View Article and Find Full Text PDFUltrasound-Enhanced Spleen-Targeted mRNA Delivery via Fluorinated PEGylated Lipid Nanoparticles for Immunotherapy.
Angew Chem Int Ed Engl
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University of Science and Technology of China School of Biomedical Engineering, Department of Polymer Science and Engineering, 96 Jinzhai Road, 230026, Hefei, CHINA.
Lipid nanoparticles (LNPs) based messenger RNA (mRNA) therapeutics hold immense promise for treating a wide array of diseases, while their nonhepatic organs targeting and insufficient endosomal escape efficiency remain challenges. For LNPs, polyethylene glycol (PEG) lipids have a crucial role in stabilizing them in aqueous medium, but they severely hinder cellular uptake and reduce transfection efficiency. In this study, we designed ultrasound (US)-assisted fluorinated PEGylated LNPs (F-LNPs) to enhance spleen-targeted mRNA delivery and transfection.
View Article and Find Full Text PDFMechanistic understanding of pH as a driving force in cancer therapeutics.
J Mater Chem B
January 2025
Department of Forensic Science, School for Bio Engineering and Bio Sciences, Lovely Professional University, Phagwara, Punjab, India.
The development of pH-directed nanoparticles for tumor targeting represents a significant advancement in cancer biology and therapeutic strategies. These innovative materials have the ability to interact with the unique acidic microenvironment of tumors. They enhance drug delivery, increase therapeutic efficacy, and reduce systemic toxicity.
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