This study aims to propose a new treatment model for glioblastoma (GBM). The combination of chemotherapy, molecular targeted therapy and radiotherapy has been achieved in a highly simultaneous manner through the application of a safe, non-toxic, locally sustained drug-releasing composite Nanofiber mesh (NFM). The NFM consisted of biodegradable poly(ε-caprolactone) with temozolomide (TMZ) and 17-allylamino-17-demethoxygeldanamycin (17AAG), which was used in radiation treatment. TMZ and 17AAG combination showed a synergistic cytotoxicity effect in the T98G cell model. TMZ and 17AAG induced a radiation-sensitization effect, respectively. The NFM containing 17AAG or TMZ, known as 17AAG-NFM and TMZ-NFM, enabled cumulative drug release of 34.1% and 39.7% within 35 days. Moreover, 17AAG+TMZ-NFM containing both drugs revealed a synergistic effect in relation to the NFM of a single agent. When combined with radiation, 17AAG+TMZ-NFM induced in an extremely powerful cytotoxic effect. These results confirmed the application of NFM can simultaneously allow multiple treatments to T98G cells. Each modality achieved a significant synergistic effect with the other, leading to a cascading amplification of the therapeutic effect. Due to the superior advantage of sustained drug release over a long period of time, NFM has the promise of clinically addressing the challenge of high recurrence of GBM post-operatively.
Glioblastoma (GBM) is a highly malignant type of brain tumour that arises from astrocytes or supportive brain tissue in adults. Although there are several therapeutic options, recurrence rates remain high, with a 5 year survival rate expectancy of less than 10%. This study investigates nanofibre meshes that enable the long-term release of temozolomide (TMZ) over a 4 week period by controlling the fibre morphologies. The nanofibre meshes were fabricated via the electrospinning of a biodegradable polymer, poly(ε-caprolactone) (PCL). The obtained meshes were flexible and implantable as a local intracranial drug delivery platform. The nanofibre meshes also carry magnetic nanoparticles (MNPs) that enable the combined therapy of hyperthermia/chemotherapy corresponding to an alternating magnetic field (AMF). The heat generation behaviour of the nanofibre meshes was successfully adjusted in a hyperthermic temperature range (∼42.6 °C). The TMZ/MNP-loaded nanofibre meshes showed a 76% reduction in the cell viability of GBM cancer (T98G) cells through the synergistic effect of hyperthermia and chemotherapy. These results indicated the potential applications of nanofibre meshes as an implantable intracranial drug delivery system as an adjunct to surgery and radiation for GBM patients.
Pancreatic cancer is among the deadliest malignancies, with few treatment options for locally advanced, unresectable cases. Conventional therapies, such as chemoradiotherapy and hyperthermia, show promise but face challenges in improving outcomes. This study introduces a novel drug delivery system using gemcitabine (GEM)-loaded layer-by-layer magnetic nanoparticles (LBL MNPs) combined with alternating magnetic field (AMF) application and X-ray irradiation to enhance therapeutic efficacy. LBL MNPs were synthesized using optimized layering techniques to achieve superior drug loading and controlled release. Human pancreatic cancer cells (PANC-1) were treated with LBL MNPs alone, with AMF-induced hyperthermia, and in combination with X-rays. The results demonstrate that the 7-layer LBL MNPs exhibited optimal cytotoxicity, significantly reducing cell viability at concentrations of 30 µg/mL and higher. Combining 7-layer LBL MNPs with AMF increased cell death in a time- and concentration-dependent manner, achieving up to 98% inhibition of cell proliferation. The addition of X-rays to the regimen demonstrated a strong synergistic effect, resulting in a 13-fold increase in cell death compared to controls. These findings highlight the potential of this integrated approach to improve outcomes in patients with pancreatic cancer.
Oxaliplatin is an anticancer drug used to treat colorectal and gastric cancers. In many cases, chemotherapy is discontinued due to adverse events caused by anticancer drugs. To address this challenge, we developed a sustained-release drug delivery system using polycaprolactone sheets embedded with oxaliplatin (oxaliplatin sheets) and evaluated their therapeutic potential in murine models of colon and gastric cancers. Antitumor efficacy was compared with conventional intraperitoneal administration by monitoring tumor volume, body weight, and systemic oxaliplatin concentrations over 21 days, along with histopathological assessment of tumors and hepatic tissue. Oxaliplatin sheets demonstrated superior tumor suppression, significantly reduced Ki-67 positivity, and mitotic indices. Additionally, antitumor effects and blood oxaliplatin levels were consistent regardless of implantation site. Notably, oxaliplatin sheets significantly decreased weight loss compared with intraperitoneal administration. In our analysis of liver pathology, we found that hepatic sinusoidal obstruction and hepatocellular degeneration were significantly increased after intraperitoneal administration compared with untreated mice and mice treated with oxaliplatin sheets. Furthermore, treatment with oxaliplatin sheets improved survival. Thus, our oxaliplatin sheets exhibited effective tumor control and reduced side effects, indicating their potential as a promising treatment for advanced gastric and colorectal cancers.