Tumortropic adipose-derived stem cells carrying smart nanotherapeutics for targeted delivery and dual-modality therapy of orthotopic glioblastoma

J Control Release. 2017 May 28:254:119-130. doi: 10.1016/j.jconrel.2017.03.035. Epub 2017 Mar 21.


Chemotherapy is typically used to treat malignant brain tumors, especially for the tumors in surgically inaccessible areas. However, owing to the existence of blood-brain barrier (BBB), the tumor accumulation and therapeutic efficacy of clinical therapeutics is still of great concerns. To this end, we present herein a prominent therapeutic strategy adopting adipose-derived stem cells (ADSCs) capable of carrying nanotherapeutic payloads selectively toward brain tumors for thermo/chemotherapy. The nanoparticle (NP) payload was obtained from co-assembly of poly(γ-glutamic acid-co-distearyl γ-glutamate) with poly(lactic-co-glycolic acid), paclitaxel (PTX), and oleic acid-coated superparamagnetic iron oxide NPs in aqueous solution. The particle size and drug loading content were ca 110nm and 8.4wt%, respectively. After being engulfed by ADSCs, the nanotherapeutics was found rather harmless to cellular hosts at a PTX concentration of 30μM over 48h in the absence of pertinent stimulus. Nevertheless, the ADSC-based approach combined with high frequency magnetic field exhibits a sound therapeutic performance with a 4-fold increase in therapeutic index on brain astrocytoma (ALTS1C1)-bearing mice (C57BL/6J) as compared to the typical chemotherapy using a current first-line chemodrug, temozolomide. Immunohistochemical examination of brain tumor sections confirms the successful cellular transport and pronounced cytotoxic action of therapeutics against tumor cells in vivo. This work demonstrates the promise of ADSC-mediated chemo/thermal therapy against brain tumors.

Keywords: Adipose-derived stem cells; Cell-based delivery; Chemo/thermal therapy; Glioblastoma multiforme; Therapeutic nanoparticles.

MeSH terms

  • Adipocytes / cytology*
  • Adipocytes / physiology
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Biological Transport
  • Blood-Brain Barrier / metabolism
  • Brain Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Survival
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / chemistry
  • Dacarbazine / pharmacology
  • Drug Carriers*
  • Drug Liberation
  • Glioblastoma / drug therapy*
  • Humans
  • Lactic Acid / chemistry
  • Magnetite Nanoparticles / chemistry*
  • Male
  • Mice, Inbred C57BL
  • Molecular Targeted Therapy
  • Oleic Acid / chemistry
  • Paclitaxel / administration & dosage
  • Paclitaxel / chemistry
  • Particle Size
  • Permeability
  • Polyglutamic Acid / chemistry
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Stem Cells*
  • Surface Properties
  • Temozolomide
  • Tissue Distribution


  • Antineoplastic Agents
  • Drug Carriers
  • Magnetite Nanoparticles
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglutamic Acid
  • Polyglycolic Acid
  • Oleic Acid
  • Lactic Acid
  • Dacarbazine
  • Paclitaxel
  • Temozolomide