Tumortropic adipose-derived stem cells carrying smart nanotherapeutics for targeted delivery and dual-modality therapy of orthotopic glioblastoma.
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.
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan.
Wen-Chia
WC
Huang
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan; Department of Surgery, Hsinchu Mackay Memorial Hospital, Hsinchu 30071, Taiwan.
I-Lin
IL
Lu
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan.
Wen-Hsuan
WH
Chiang
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan.
Yi-Wen
YW
Lin
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan.
Yuan-Chung
YC
Tsai
Department of Chemical Engineering, National Chung Hsing University, Taichung 402, Taiwan.
Hsin-Hung
HH
Chen
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan.
Chien-Wen
CW
Chang
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan.
Chi-Shiun
CS
Chiang
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan. Electronic address: hscchiu@mx.nthu.edu.tw.
Hsin-Cheng
HC
Chiu
D017667:Adipocytes / Q000166:cytology* / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers; D065546:Drug Liberation; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy; D019301:Oleic Acid / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D010539:Permeability; D011099:Polyglutamic Acid / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013234:Stem Cells; D013499:Surface Properties; D000077204:Temozolomide; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011099:Polyglutamic Acid; D011100:Polyglycolic Acid; D019301:Oleic Acid; D019344:Lactic Acid; D003606:Dacarbazine; D017239:Paclitaxel; D000077204:Temozolomide
Adipose-derived stem cells; Cell-based delivery; Chemo/thermal therapy; Glioblastoma multiforme; Therapeutic nanoparticles