title: Nanoparticle mediated co-delivery of paclitaxel and a TLR-4 agonist results in tumor regression and enhanced immune response in the tumor microenvironment of a mouse model.
abstract: Inefficiency of cancer chemotherapy to improve life expectancy in majority of patients raises serious concern and warrants development of novel therapeutic strategies. Immunotherapy in combination with chemotherapy has shown promising outcomes in recent years. Herein, we report better tumor regression and enhancement of antitumor immune response at the tumor microenvironment by co-delivery of paclitaxel and a TLR4 agonist through a PLGA based nanoparticle preparation (TLNP). Particle characterization showed high encapsulation of both components and retention of their biological activities. In vivo tumor regression studies demonstrated clear benefit of TLNP over the paclitaxel. The mean tumor volume of the TLNP treated animals was found to be 40% less than that of the Paclitaxel treated animals. Flow cytometric analysis of tumor infiltrating immune cells indicated activation of antigen presenting cells and T-cells providing evidence of Th1 immune response. In vivo results are promising and could pave way for novel chemo-immunotherapeutic treatment modality.
authors: Product Development Cell-I, National Institute of Immunology, New Delhi 110067, India.
authors: Aniruddha
authors: A
authors: Roy
authors: Manu Smriti
authors: MS
authors: Singh
authors: Pramod
authors: P
authors: Upadhyay
authors: Sangeeta
authors: S
authors: Bhaskar
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051197:Toll-Like Receptor 4 / Q000819:agonists; D047368:Tumor Burden / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017239:Paclitaxel