title: Protamine-carboxymethyl cellulose magnetic nanocapsules for enhanced delivery of anticancer drugs against drug resistant cancers.
abstract: Multidrug resistance is a major therapeutic challenge faced in the conventional chemotherapy. Nanocarriers are beneficial in the transport of chemotherapeutics by their ability to bypass the P-gp efflux in cancers. Most of the P-gp inhibitors under phase II clinical trial are facing failures and hence there is a need to develop a suitable carrier to address P-gp efflux in cancer therapy. Herein, we prepared novel protamine and carboxymethyl cellulose polyelectrolyte multi-layered nanocapsules modified with Fe3O4 nanoparticles for the delivery of doxorubicin against highly drug resistant HeLa cells. The experimental results revealed that improved cellular uptake, enhanced drug intensity profile with greater percentage of apoptotic cells was attained when doxorubicin loaded magnetic nanocapsules were used in the presence of external magnetic field. Hence, we conclude that this magnetic field assisted nanocapsule system can be used for delivery of chemotherapeutics for potential therapeutic efficacy at minimal dose in multidrug resistant cancers.
  
  
  BACKGROUND
  Many cancer drugs fail when cancer cells become drug resistant. Indeed, multidrug resistance (MDR) is a major therapeutic challenge. One way that tumor cells attain MDR is by over expression of molecular pumps comprising of P-glycoprotein (P-gp) and multidrug resistant proteins (MRP), which can expel chemotherapeutic drugs out of the cells. In this study, the authors prepared novel protamine and carboxymethyl cellulose polyelectrolyte multi-layered nanocapsules modified with Fe3O4 nanoparticles for the delivery of doxorubicin. The results show that there was better drug delivery and efficacy even against MDR tumor cells.
authors: Dept. of Materials Engineering, Indian Institute of Science, Bangalore.
authors: Rajasegaran
authors: R
authors: Elumalai
authors: Dept. of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore.
authors: Shilpa
authors: S
authors: Patil
authors: Dept. of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore.
authors: Naseer
authors: N
authors: Maliyakkal
authors: Dept. of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore.
authors: Annapoorni
authors: A
authors: Rangarajan
authors: Dept. of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore.
authors: Paturu
authors: P
authors: Kondaiah
authors: Dept. of Materials Engineering, Indian Institute of Science, Bangalore. Electronic address: amr@materials.iisc.ernet.in.
authors: Ashok M
authors: AM
authors: Raichur
mesh_terms: D002266:Carboxymethylcellulose Sodium / Q000737:chemistry / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D053769:Nanocapsules / Q000191:economics*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011479:Protamines / Q000737:chemistry / Q000494:pharmacology
chemical_list: D058185:Magnetite Nanoparticles; D053769:Nanocapsules; D011479:Protamines; D004317:Doxorubicin; D002266:Carboxymethylcellulose Sodium
keywords: Apoptosis; Doxorubicin delivery; Drug resistant cells; Magnetic nanocapsules; Targeted delivery