title: Methotrexate-Loaded Four-Arm Star Amphiphilic Block Copolymer Elicits CD8+ T Cell Response against a Highly Aggressive and Metastatic Experimental Lymphoma.
abstract: We have synthesized a well-defined four-arm star amphiphilic block copolymer [poly(DLLA)-b-poly(NVP)]4 [star-(PDLLA-b-PNVP)4] that consists of D,L-lactide (DLLA) and N-vinylpyrrolidone (NVP) via the combination of ring-opening polymerization (ROP) and xanthate-mediated reversible addition-fragmentation chain transfer (RAFT) polymerization. Synthesis of the polymer was verified by 1H NMR spectroscopy and gel permeation chromatography (GPC). The amphiphilic four-arm star block copolymer forms spherical micelles in water as demonstrated by transmission electron microscopy (TEM) and 1H NMR spectroscopy. Pyrene acts as a probe to ascertain the critical micellar concentration (cmc) by using fluorescence spectroscopy. Methotrexate (MTX)-loaded polymeric micelles of star-(PDLLA15-b-PNVP10)4 amphiphilic block copolymer were prepared and characterized by fluorescence and TEM studies. Star-(PDLLA15-b-PNVP10)4 copolymer was found to be significantly effective with respect to inhibition of proliferation and lysis of human and murine lymphoma cells. The amphiphilic block copolymer causes cell death in parental and MTX-resistant Dalton lymphoma (DL) and Raji cells. The formulation does not cause hemolysis in red blood cells and is tolerant to lymphocytes compared to free MTX. Therapy with MTX-loaded star-(PDLLA15-b-PNVP10)4 amphiphilic block copolymer micelles prolongs the life span of animals with neoplasia by reducing the tumor load, preventing metastasis and augmenting CD8+ T cell-mediated adaptive immune responses.
authors: Immunobiology Laboratory, Department of Zoology, Faculty of Science, Banaras Hindu University , Varanasi 221005, India.|Department of Zoology, The University of Burdwan , Burdwan 713104, West Bengal, India.
authors: Sumit Kumar
authors: SK
authors: Hira
authors: Department of Chemistry, Faculty of Science, Banaras Hindu University , Varanasi 221005, India.|School of Biomedical Engineering, Indian Institute of Technology ( Banaras Hindu University ), Varanasi 221005, India.
authors: Kalyan
authors: K
authors: Ramesh
authors: Immunobiology Laboratory, Department of Zoology, Faculty of Science, Banaras Hindu University , Varanasi 221005, India.
authors: Uttam
authors: U
authors: Gupta
authors: Department of Chemistry, Faculty of Science, Banaras Hindu University , Varanasi 221005, India.
authors: Kheyanath
authors: K
authors: Mitra
authors: School of Biomedical Engineering, Indian Institute of Technology ( Banaras Hindu University ), Varanasi 221005, India.
authors: Nira
authors: N
authors: Misra
authors: Department of Chemistry, Faculty of Science, Banaras Hindu University , Varanasi 221005, India.
authors: Biswajit
authors: B
authors: Ray
authors: Immunobiology Laboratory, Department of Zoology, Faculty of Science, Banaras Hindu University , Varanasi 221005, India.
authors: Partha Pratim
authors: PP
authors: Manna
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D004912:Erythrocytes / Q000166:cytology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008223:Lymphoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008727:Methotrexate / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D051379:Mice; D008806:Mice, Inbred AKR; D008823:Micelles; D009362:Neoplasm Metastasis; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D011721:Pyrenes / Q000737:chemistry; D014183:Transplantation, Heterologous
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D011721:Pyrenes; C030984:pyrene; D008727:Methotrexate
keywords: drug delivery; drug resistance; hemocompatibility; lymphoma; methotrexate; star-[poly(DLLA)-b-poly(NVP)]4