title: Formulation and antitumorigenic activities of nanoencapsulated nifetepimine: A promising approach in treating triple negative breast carcinoma.
abstract: Triple negative breast cancer (TNBC) is one of the most common invasive malignancies among women, associated with poor prognosis. Standard chemotherapy targets all dividing cells, resulting in dose-limiting toxicities. In this study, we demonstrated a strategy of encapsulating a hydrophobic synthetic compound, nifetepimine, having anticancer properties, in poly (lactic-co-glycolic acid) nanoparticles to increase selectivity of drug to cancerous cells with minimum toxicity towards normal cells. Nanoencapsulated nifetepimine (30-100nm) having loading and encapsulation efficiency of 7.45% and 75% respectively, was successfully internalized inside TNBC cells upon sustained release resulting in apoptosis. An in vivo bio-distribution study indicated that nanonifetepimine selectively accumulated into breast tumor sites of mice, primarily due to prolonged blood circulation time and binding of nifetepimine to epidermal growth factor receptor that remains overexpressed in most of the TNBC tumors. Moreover, we observed significant reduction in breast tumor volume with improved survival implying high tumor targetability of nanonifetepimine.
authors.affiliation: Division of Molecular Medicine, Bose Institute, Centenary Campus, Kolkata, India.
authors.forename: Aparajita
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Cancer Biology and Inflammatory Disorder, Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Arijit
authors.initials: A
authors.lastname: Bhowmik
authors.affiliation: Division of Molecular Medicine, Bose Institute, Centenary Campus, Kolkata, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Bhandary
authors.affiliation: Department of Chemistry, Maulana Azad College, Kolkata, India.
authors.forename: Salil
authors.initials: S
authors.lastname: Putatunda
authors.affiliation: Structural Biology and Bioinformatics Division, Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Aparna
authors.initials: A
authors.lastname: Laskar
authors.affiliation: Chemistry Division, Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Atanu
authors.initials: A
authors.lastname: Biswas
authors.affiliation: Structural Biology and Bioinformatics Division, Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Sandip
authors.initials: S
authors.lastname: Dolui
authors.affiliation: Division of Molecular Medicine, Bose Institute, Centenary Campus, Kolkata, India.
authors.forename: Bhaswati
authors.initials: B
authors.lastname: Banerjee
authors.affiliation: Cancer Biology and Inflammatory Disorder, Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Rajni
authors.initials: R
authors.lastname: Khan
authors.affiliation: Department of Biotechnology, Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Nirmalendu
authors.initials: N
authors.lastname: Das
authors.affiliation: Department of Chemistry, Maulana Azad College, Kolkata, India.
authors.forename: Arijit
authors.initials: A
authors.lastname: Chakraborty
authors.affiliation: Cancer Biology and Inflammatory Disorder, Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Mrinal Kanti
authors.initials: MK
authors.lastname: Ghosh
authors.affiliation: Division of Molecular Medicine, Bose Institute, Centenary Campus, Kolkata, India. Electronic address: parimalsen.boseinst@gmail.com.
authors.forename: Parimal C
authors.initials: PC
authors.lastname: Sen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001940:Breast; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D053758:Nanoparticles; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000494:pharmacology; D014018:Tissue Distribution; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D011744:Pyrimidinones; C576638:ethyl 4-(3-nitro)-phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
keywords: Epidermal growth factor receptor; Nanoparticles; Nifetepimine; Poly (lactic-co-glycolic acid); Triple negative breast cancer; Tumor targeting