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

• Published in: Journal of controlled release Vol. 254; pp. 119 - 130
• Main Authors: Huang, Wen-Chia, Lu, I.-Lin, Chiang, Wen-Hsuan, Lin, Yi-Wen, Tsai, Yuan-Chung, Chen, Hsin-Hung, Chang, Chien-Wen, Chiang, Chi-Shiun, Chiu, Hsin-Cheng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 28.05.2017
• Subjects: Adipocytes - cytology; Adipocytes - physiology; Adipose-derived stem cells; 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; Cell-based delivery; Chemo/thermal therapy; Dacarbazine - analogs & derivatives; Dacarbazine - chemistry; Dacarbazine - pharmacology; Drug Carriers; Drug Liberation; Glioblastoma - drug therapy; Glioblastoma multiforme; 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; Stem Cells; Surface Properties; Therapeutic nanoparticles; Tissue Distribution; Adipose-derived stem cells; Therapeutic nanoparticles; Chemo/thermal therapy; Glioblastoma multiforme; Cell-based delivery
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2017.03.035

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. [Display omitted]