The superparamagnetic properties of magnetic nanoparticles (MNPs) allow them to be guided by an externally positioned magnet and also provide contrast for MRI. However, their therapeutic use in treating CNS pathologies in vivo is limited by insufficient local accumulation and retention resulting from their inability to traverse biological barriers. The combined use of focused ultrasound and magnetic targeting synergistically delivers therapeutic MNPs across the blood–brain barrier to enter the brain both passively and actively. Therapeutic MNPs were characterized and evaluated both in vitro and in vivo, and MRI was used to monitor and quantify their distribution in vivo. The technique could be used in normal brains or in those with tumors, and significantly increased the deposition of therapeutic MNPs in brains with intact or compromised blood–brain barriers. Synergistic targeting and image monitoring are powerful techniques for the delivery of macromolecular chemotherapeutic agents into the CNS under the guidance of MRI.

The purpose of this study is to assess the preclinical therapeutic efficacy of magnetic resonance imaging (MRI)-monitored focused ultrasound (FUS)-induced blood-brain barrier (BBB) disruption to enhance Temozolomide (TMZ) delivery for improving Glioblastoma Multiforme (GBM) treatment. MRI-monitored FUS with microbubbles was used to transcranially disrupt the BBB in brains of Fisher rats implanted with 9L glioma cells. FUS-BBB opening was spectrophotometrically determined by leakage of dyes into the brain, and TMZ was quantitated in cerebrospinal fluid (CSF) and plasma by LC-MS\MS. The effects of treatment on tumor progression (by MRI), animal survival and brain tissue histology were investigated. Results demonstrated that FUS-BBB opening increased the local accumulation of dyes in brain parenchyma by 3.8-/2.1-fold in normal/tumor tissues. Compared to TMZ alone, combined FUS treatment increased the TMZ CSF/plasma ratio from 22.7% to 38.6%, reduced the 7-day tumor progression ratio from 24.03 to 5.06, and extended the median survival from 20 to 23 days. In conclusion, this study provided preclinical evidence that FUS BBB-opening increased the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting its clinical potential for improving current brain tumor treatment.

Focused ultrasound (FUS) exposure with the presence of microbubbles has been shown to transiently open the blood-brain barrier (BBB), and thus has potential to enhance the delivery of various kinds of therapeutic agents into brain tumors. The purpose of this study was to assess the preclinical therapeutic efficacy of FUS-BBB opening for enhanced temozolomide (TMZ) delivery in glioma treatment. FUS exposure with microbubbles was delivered to open the BBB of nude mice that were either normal or implanted with U87 human glioma cells. Different TMZ dose regimens were tested, ranging from 2.5 to 25 mg/kg. Plasma and brain samples were obtained at different time-points ranging from 0.5 to 4 hours, and the TMZ concentration within samples was quantitated via a developed LC-MS/MS procedure. Tumor progression was followed with T2-MRI, and animal survival and brain tissue histology were conducted. Results demonstrated that FUS-BBB opening caused the local TMZ accumulation in the brain to increase from 6.98 to 19 ng/mg. TMZ degradation time in the tumor core was found to increase from 1.02 to 1.56 hours. Improved tumor progression and animal survival were found at different TMZ doses (up to 15% and 30%, respectively). In conclusion, this study provides preclinical evidence that FUS-BBB opening increases the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting the potential for clinical application to improve current brain tumor treatment.

In clinical tumor therapy, chemotherapeutic routes have caused severe side effects; current delivery methods are unsatisfactory. Successful design of a remotely folate (FA)-grafted chitosan (CS)-coated magnetic nanoparticle (MNP) with low toxicity, has been achieved. A chemotherapeutic drug such as doxorubicin (DOX), is loaded in the MNP-based matrix (FA-grafted CS-DOX-_TPP-MNP), which is coated by an activated target tumor molecule of FA-grafted CS biopolymer with the inclusion of tripolyphosphate (TPP) as a linker. The resultant nano-complexes exhibited random aggregates (~240 nm) and zeta potential (−24.9 mV). In vivo experiments using athymic BALB/c nude mice with human glioblastoma U87 cells in a subcutaneous tumor model revealed that magnetic guidance of FA-grafted CS-DOX-_TPP-MNP, injected via the tail vein, significantly decreased tumor growth. This manuscript demonstrates the feasibility of magnetizing control of FA-grafted CS-DOX-_TPP-MNP to enhance the localization of drug release.

The piezoresistive characteristics of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) pressure sensors with inter-digitated (IDE) and cross-point electrode (CPE) structures have been investigated. A small variation of the resistance of the pressure sensors with IDE without bottom indium-tin-oxide (b-ITO) film and with CPE structures was observed owing to the single carrier-conducting pathway. For the IDE pressure sensors with b-ITO, the piezoresistive characteristics at low and high pressure were similar to those of the pressure sensors with IDE without b-ITO and with CPE structures, respectively, leading to increased piezoresistive pressure sensitivity as the PEDOT:PSS film thickness decreased. A maximum sensitivity of more than 42 kΩ/Pa was achieved. When the normal pressure was applied, the increased number of conducting points or the reduced distance between the PEDOT oligomers within the PEDOT:PSS film resulted in a decrease of the resistance. The piezoresistive pressure sensors with a single carrier-conducting pathway, i.e., IDE without b-ITO and CPE structures, exhibited a small relaxation time and a superior reversible operation, which can be advantageous for fast piezoresistive response applications.