title: Anticancer and immunostimulatory activity by conjugate of paclitaxel and non-toxic derivative of LPS for combined chemo-immunotherapy.
abstract: OBJECTIVE
  Cancer is a multifactorial syndrome; hence, multidimensional therapy with a chemo-immunotherapeutic conjugate could be more effective in curing the disease.
  
  
  METHODS
  We used SP-LPS, a bio-polymer having potent immunostimulatory activity, for conjugation with paclitaxel to make a chemo-immunotherapeutic conjugate. Its physicochemical characterization was done by HPLC, NMR and IR spectra. Stability was measured at different pH, temperature and in tissue homogenates. Chemotherapeutic and immunostimulatory activity was evaluated in vitro and also in tumor microenvironment.
  
  
  RESULTS
  The conjugate self assembled into nanoparticulate structure, probably due to micelle formation. Stability was pH and temperature dependent. The conjugate exhibited chemotherapeutic and immunotherapeutic activity in vitro. In vivo antitumor activity was significantly higher and a higher percentage of activated immune cells were found in the tumor microenvironment of the conjugate-treated mice as compared to Taxol®-treated group.
  
  
  CONCLUSIONS
  This conjugate is a potential chemo-immunotherapeutic compound for the treatment of cancer with advantages over present day chemotherapy with Taxol in terms of higher anticancer activity, less toxicity and ease of delivery.
authors.affiliation: Product Development Cell-I, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Aniruddha
authors.initials: A
authors.lastname: Roy
authors.forename: Sourav
authors.initials: S
authors.lastname: Chandra
authors.forename: Swapna
authors.initials: S
authors.lastname: Mamilapally
authors.forename: Pramod
authors.initials: P
authors.lastname: Upadhyay
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Bhaskar
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D007167:Immunotherapy; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000276:Adjuvants, Immunologic; D000972:Antineoplastic Agents, Phytogenic; D008070:Lipopolysaccharides; D017239:Paclitaxel