Increasing the anticancer activity of azidothymidine toward the breast cancer via rational design of magnetic drug carrier based on molecular imprinting technology

Mater Sci Eng C Mater Biol Appl. 2019 Oct:103:109771. doi: 10.1016/j.msec.2019.109771. Epub 2019 May 21.

Abstract

Cancer treatment based anticancer drugs face serious obstacles. To prevail these obstacles, an effective targeted drug carrier can be imperative. This study aimed to design rationally an imprinting strategy for the carrying of a model anticancer drug, Azidothymidine via molecular imprinting technology. Considering the identity and affinity of monomers and cross-linkers to AZT, this work succeeded to establish an exclusive procedure to significantly improve the process of imprinting the Azidothymidine. Imprinting process was carried out on the surface of vinyl-modified silica coated Fe3O4 nanoparticles toward the delivery of azidothymidine to targeted tissue by external magnetic field. The resultant carrier was characterized by FT-IR, XRD, VSM, FESEM, EDX, BET, TGA. The AZT loading process on the nanocarrier is followed with Freundlich adsorption isotherm (QMAX:170 mg/g) and pseudo-second order fast adsorption kinetic (5 min). The release process of AZT from nanocarrier was fitted with First-Order and Higuchi dynamic model. Eventually, the involvement of magnetic nanocarrier was investigated on apoptosis in MCF-7 (cancer cell line) and MCF-10 (normal cell line). The cytotoxicity percentage on MCF-7 cells for magnetic nanocarrier was about 49 times greater than the azidothymidine, but did not affect MCF-10 cells. The corresponding results appropriately disclosed that the cytotoxicity of proposed nanocarrier on MCF-7 cells is through the caspase3 activity. The drug loading and release process as well as in-vitro studies of magnetic carrier were compared with bare carrier. This study indicates that the proposed magnetic carrier can be used as a promising drug carrier toward the breast cancer treatment.

Keywords: Apoptosis; Azidothymidine; Cytotoxicity; Molecular imprinting technology; Targeted drug carrier; caspase3.

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Drug Carriers* / chemistry
  • Drug Carriers* / pharmacology
  • Female
  • Humans
  • MCF-7 Cells
  • Magnetite Nanoparticles* / chemistry
  • Magnetite Nanoparticles* / therapeutic use
  • Molecular Imprinting*
  • Zidovudine* / chemistry
  • Zidovudine* / pharmacology

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Magnetite Nanoparticles
  • Zidovudine