Anti-CD133 Antibody-Targeted Therapeutic Immunomagnetic Albumin Microbeads Loaded with Vincristine-Assisted to Enhance Anti-Glioblastoma Treatment

Mol Pharm. 2019 Nov 4;16(11):4582-4593. doi: 10.1021/acs.molpharmaceut.9b00704. Epub 2019 Oct 15.

Abstract

Poor uptake of antitumor drugs by tumor cells is a critical challenge for anticancer therapeutics. Moreover, the deficiency of specific tumor selectivity for tumor sites may further limit the therapeutic efficacy and cause side effects in healthy regions of the body. Vincristine (VCR) is an effective antitumor drug; however, because of its severe nerve toxicity, short half-life, and fast metabolism, its clinical application is limited. Herein, novel anti-CD133 monoclonal antibody (CD133mAb)-targeted therapeutic immunomagnetic albumin microbeads (CD133mAb/TMAMbs) are smartly constructed for enhancing antiglioblastoma treatment. Superparamagnetic iron oxide nanoparticles (SPIO NPs) were first fabricated as nanocarrier cores, then encapsulated with human serum albumin (HSA), and loaded antitumor drug VCR. Then CD133mAb, which has specific affinity with the cell membrane CD133, was subsequently conjugated to form CD133mAb-decorated therapeutic immunomagnetic albumin microbeads (CD133mAb/TMAMbs). The influence of CD133mAb/TMAMbs on the viability, cell cycle, apoptosis, cell cytoskeleton, migration, and invasion of CD133-overexpressing U251 cells was explored. The CD133mAb-conjugated magnetic albumin microbeads exhibited a high drug loading capacity, stability and hemocompatibility, and active targeting ability by specific recognition of the CD133 surface antigen by the bioconjugation of CD133mAb. More importantly, the constructed therapeutic CD133mAb/TMAMbs have a specifically effective uptake via the CD133 transmembrane protein that is overexpressed in U251 glioblastoma cells and displayed an effective antitumor proliferation and invasive ability. Therefore, based on these results, the fabricated CD133mAb/TMAMbs demonstrate promising uses in brain cancer-targeted diagnosis and therapy.

Keywords: CD133mAb; drug delivery systems (DDS); magnetic albumin microbeads (MAMbs); vincristine (VCR).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen / metabolism*
  • Albumins / metabolism*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Delivery Systems / methods
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Humans
  • Magnetics / methods
  • Microspheres
  • Nanoparticles / chemistry
  • Vincristine / pharmacology*

Substances

  • AC133 Antigen
  • Albumins
  • Antineoplastic Agents
  • PROM1 protein, human
  • Vincristine