title: A rationally designed photo-chemo core-shell nanomedicine for inhibiting the migration of metastatic breast cancer cells followed by photodynamic killing.
abstract: A multifunctional core-shell nanomedicine capable of inhibiting the migratory capacity of metastatic cancer cells followed by imparting cytotoxic stress by photodynamic action is reported. Based on in silico design, we have developed a core-shell nanomedicine comprising of ~80nm size poly(lactic-co-glycolic acid) (PLGA) nano-core encapsulating photosensitizer, m-tetra(hydroxyphenyl)chlorin (mTHPC), and ~20nm size albumin nano-shell encapsulating tyrosine kinase inhibitor, Dasatinib, which impair cancer migration. This system was prepared by a sequential process involving electrospray of polymer core and coacervation of protein shell. Cell studies using metastatic breast cancer cells demonstrated disruption of Src kinase involved in the cancer migration by albumin-dasatinib nano-shell and generation of photoactivated oxidative stress by mTHPC-PLGA nano-core. This unique combinatorial photo-chemo nanotherapy resulted synergistic cytotoxicity in ~99% of the motility-impaired metastatic cells. This approach of blocking cancer migration followed by photodynamic killing using rationally designed nanomedicine is a promising new strategy against cancer metastasis.
  
  
  BACKGROUND
  A multifunctional core-shell nanomedicine capable of inhibiting metastatic cancer cell migration, in addition to inducing photodynamic effects, is described in this paper. The authors document cytotoxicity in approximately 99% of the studied metastatic breast cancer cells. Similar approaches would be a very welcome addition to the treatment protocols of advanced metastatic breast cancer and other types of neoplasms.
authors.affiliation: Amrita center for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (University), Kochi, India.
authors.forename: Giridharan Loghanathan
authors.initials: GL
authors.lastname: Malarvizhi
authors.affiliation: Amrita center for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (University), Kochi, India.
authors.forename: Parwathy
authors.initials: P
authors.lastname: Chandran
authors.affiliation: Amrita center for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (University), Kochi, India.
authors.forename: Archana Payickattu
authors.initials: AP
authors.lastname: Retnakumari
authors.affiliation: Amrita center for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (University), Kochi, India.
authors.forename: Ranjith
authors.initials: R
authors.lastname: Ramachandran
authors.affiliation: Amrita center for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (University), Kochi, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Gupta
authors.affiliation: Amrita center for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (University), Kochi, India.
authors.forename: Shantikumar
authors.initials: S
authors.lastname: Nair
authors.affiliation: Amrita center for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (University), Kochi, India. Electronic address: manzoork@aims.amrita.edu.
authors.forename: Manzoor
authors.initials: M
authors.lastname: Koyakutty
mesh_terms: D001940:Breast / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D000069439:Dasatinib; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008652:Mesoporphyrins / Q000008:administration & dosage* / Q000627:therapeutic use; D062105:Molecular Docking Simulation; D050997:Nanomedicine / Q000379:methods; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000627:therapeutic use; D012709:Serum Albumin / Q000737:chemistry; D013844:Thiazoles / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D004337:Drug Carriers; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D011743:Pyrimidines; D012709:Serum Albumin; D013844:Thiazoles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011505:Protein-Tyrosine Kinases; C072269:temoporfin; D000069439:Dasatinib
keywords: Albumin; Core-shell nanomedicine; Metastasis; PLGA; Photodynamic therapy