Abstract
To improve the therapeutic efficacy of solid brain tumors by promoting tumor-targeted chemotherapy delivery and triggering drug release upon external alternating magnetic field, the tumor-tropic adipose-derived stem cells were exploited as a vehicle to carry the superparamagnetic iron oxide nanoparticles (SPION)/ paclitaxel (PTX) -loaded nanoparticles. The PTX and oleic acid-coated SPIONs were hydrophobically entrapped in the poly(lactic-co-glycolic acid)-based cores stabilized by amphiphilic lipid-containing copolymer, poly(γ-glutamic acid-co-distearin glutamate).While the particle size and polydispersity index were evaluated to be ca 106 nm and 0.11, respectively, the SPION / PTX -loaded nanoparticles were featured with a high drug loading efficiency (91.9%), corresponding to a loading capacity of 8.4 wt%. The in vitro results demonstrate that the SPION / PTX -loaded nanoparticles after being engulfed by stem cells are benign to the cellular host, thereby allowing the host to retain their innate tumor tropism. The in vivo fluorescence images reveal that the Cy5.5-labeled nanoparticles transported by tumor-homing stem cells display the considerably enhanced accumulation in the brain tumor of the ALTS1C1 intracranial tumor-bearing mice. Notably, the survival rate of the ALTS1C1 intracranial tumor-bearing mice subjected to the payload-containing stem cells via tail vein injection and high frequency magnetic field (HFMF) was significantly enhanced as compared to that of tumor-bearing mice receiving SPION / PTX -loaded nanoparticles alone. Furthermore, the treatment combining payload-containing stem cells and HFMF stimulus exhibited the superior capability of inhibiting tumor growth of the ALTS1C1 subcutaneous tumor-bearing mice. Based on the above results, the use of tumor-tropic stem cells to deliver therapeutic nanoparticles combined with the external remotely-controlled drug release shows the great potential for brain tumor treatment.