title: An in-vivo study for targeted delivery of copper-organic complex to breast cancer using chitosan polymer nanoparticles.
abstract: We have developed a strategy for targeted delivery of metal-diketo complex, "bis(2,4-pentanedionato) copper(II)" to breast cancer cells both in-vitro and in-vivo. This metal-organic complex induced ROS and subsequently DNA damage as well as mitochondrial membrane depolarization was observed. The mitochondria rupture further triggered apoptosis. For in-vitro targeting strategies, two different approaches were employed, folic acid or her-2 specific peptide (KCCYSL) was attached to stearic acid-modified polymeric Chitosan nanoparticles loaded with metal-organic complex "bis(2,4-pentanedionato)copper(II)". This was tested on two pairs of isogenic cells (FR+/FR- MCf-7 and her2+ /her2- MCF-7) and it was observed that cells expressing the receptor were susceptible to the drug whereas non-expressing isogenic cells were almost un-affected. During in-vivo studies, mice receiving targeted delivery of bis(2,4-pentanedionato) copper (II) had increased survivability and reduced tumor volume compared to non-targeted drug delivery. During toxicity studies for liver enzymes it was also found that the mice receiving targeted drug did not show any sign of liver damage as well as other histology changes.
authors: Department of Life Science and Biotechnology, Jadavpur University, Kolkata 700 032, India.
authors: Arindam
authors: A
authors: Pramanik
authors: Department of Life Science and Biotechnology, Jadavpur University, Kolkata 700 032, India; Division of Molecular Medicine, Bose Institute, Kolkata, 700054, India.
authors: Dipranjan
authors: D
authors: Laha
authors: Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore 721 102, West Bengal, India.
authors: Sandeep Kumar
authors: SK
authors: Dash
authors: Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore 721 102, West Bengal, India.
authors: Sourav
authors: S
authors: Chattopadhyay
authors: Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore 721 102, West Bengal, India.
authors: Somenath
authors: S
authors: Roy
authors: GLA University, Mathura, Uttar Pradesh 281406, India.
authors: Dipak Kumar
authors: DK
authors: Das
authors: GLA University, Mathura, Uttar Pradesh 281406, India.
authors: Panchanan
authors: P
authors: Pramanik
authors: Department of Life Science and Biotechnology, Jadavpur University, Kolkata 700 032, India. Electronic address: pkarmakar_28@yahoo.co.in.
authors: Parimal
authors: P
authors: Karmakar
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D048271:Chitosan / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003300:Copper / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006018:Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D006018:Glycols; D010455:Peptides; C065140:2,4-pentanediol; D003300:Copper; D048271:Chitosan
keywords: Biopolymer; Breast cancer; Copper; Nanoparticle; Targeted drug delivery