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Tumortropic adipose-derived stem cells carrying smart nanotherapeutics for targeted delivery and dual-modality therapy of orthotopic glioblastoma
- Source :
- Journal of controlled release : official journal of the Controlled Release Society. 254
- Publication Year :
- 2016
-
Abstract
- 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 110 nm and 8.4 wt%, respectively. After being engulfed by ADSCs, the nanotherapeutics was found rather harmless to cellular hosts at a PTX concentration of 30 μM over 48 h 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/6 J) 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.
- Subjects :
- 0301 basic medicine
Male
Pathology
medicine.medical_treatment
Pharmaceutical Science
02 engineering and technology
chemistry.chemical_compound
Polylactic Acid-Polyglycolic Acid Copolymer
Cell Movement
Adipocytes
Cytotoxic T cell
Tissue Distribution
Molecular Targeted Therapy
Magnetite Nanoparticles
Drug Carriers
Brain Neoplasms
Stem Cells
021001 nanoscience & nanotechnology
Dacarbazine
Paclitaxel
Polyglutamic Acid
Blood-Brain Barrier
Stem cell
0210 nano-technology
medicine.drug
medicine.medical_specialty
Cell Survival
Surface Properties
Brain tumor
Antineoplastic Agents
Permeability
03 medical and health sciences
Therapeutic index
In vivo
Cell Line, Tumor
medicine
Temozolomide
Animals
Humans
Lactic Acid
Particle Size
Chemotherapy
business.industry
Biological Transport
medicine.disease
Mice, Inbred C57BL
Drug Liberation
030104 developmental biology
chemistry
Cancer research
business
Glioblastoma
Polyglycolic Acid
Oleic Acid
Subjects
Details
- ISSN :
- 18734995
- Volume :
- 254
- Database :
- OpenAIRE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Accession number :
- edsair.doi.dedup.....0ad3f6613bb0335283e5145b52a1d592