Journal
JOURNAL OF CONTROLLED RELEASE
Volume 254, Issue -, Pages 119-130Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2017.03.035
Keywords
Adipose-derived stem cells; Therapeutic nanoparticles; Cell-based delivery; Chemo/thermal therapy; Glioblastoma multiforme
Funding
- Ministry of Science and Technology [MOST 105-2221-E-007-043-MY3, MOST 104-2627-M-007-009]
- National Tsing Hua University, Taiwan [102N2733E1, 104N2742E1, 104N2046E1]
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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(gamma-glutamic acid-co-distearyl gamma-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 mu M 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.
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