Post-operative chemotherapy is still required for the treatment of glioblastoma (GBM), for which nanocarrier-based drug delivery has been identified as one of the most effective methods. However, the blood-brain barrier (BBB) and non-specific delivery to non-tumor tissues can significantly limit drug accumulation in tumor tissues and cause damage to nearby normal tissues. This study describes a targeted cancer therapy approach that uses AS1411 aptamer-conjugated nanospheres (100–300 nm in size) loaded with doxorubicin (Dox) to selectively identify tumor cells overexpressing nucleolin (NCL) proteins. The study demonstrates that the active target model, which employs aptamer-mediated drug delivery, is more effective than non-specific enhanced permeability and maintenance (EPR)-mediated delivery and passive drug delivery in improving drug penetration and maintenance in tumor cells. Additionally, the study reveals the potential for anti-cancer effects through 3D spheroidal and in vivo GBM xenograft models. The DNA-protein hybrid nanospheres utilized in this study offer numerous benefits, such as efficient synthesis, structural stability, high drug loading, dye labeling, biocompatibility, and biodegradability. When combined with nanospheres, the 1411 aptamer has been shown to be an effective drug delivery carrier allowing for the precise targeting of tumors. This combination has the potential to produce anti-tumor effects in the active targeted therapy of GBM.

Background/Aim: Poly (ADP-ribose) polymerase (PARP) inhibition could enhance the efficacy of temozolomide and prolong survival in patients with glioblastoma. The aim of this study was to evaluate the combination of the PARP inhibitor olaparib with temozolomide in the treatment of glioblastoma. Materials and Methods: The in vitro and in vivo antitumor effects of the PARP inhibitor olaparib together with temozolomide were evaluated. The in vitro experimental glioblastoma model involved O⁶-methylguanine methyltransferase (MGMT) promoter-methylated (U87MG, U251MG) and MGMT promoter-unmethylated (T98G) glioblastoma cell lines using In this model cell viability and apoptosis were assessed. For the in vivo studies, nude mice bearing orthotopically xenografted glioblastoma cell lines (U87MG) were randomized to four experimental groups: i) the untreated, ii) temozolomide alone, iii) olaparib alone and iv) olaparib and temozolomide combination groups. Mice were treated daily for 4 weeks and monitored for tumor growth and survival. Results: In vitro we found that the combination of olaparib with temozolomide enhanced temozolomide-induced cytotoxicity in all glioblastoma cell lines regardless of the status of MGMT promoter methylation. In vivo, mice treated with temozolomide alone or in combination with olaparib showed greater survival than those untreated or with the olaparib monotherapy, as well as significantly decreased tumor volume. There was no significant difference in survival and tumor volume between temozolomide alone and the combination treatment. Conclusion: The combination of the PARP inhibitor olaparib with temozolomide could be promising candidates for combination therapy of glioblastoma regardless of the MGMT promoter methylation status.

The skull base reconstruction step, which prevents cerebrospinal fluid (CSF) leakage, is one of the most challenging steps in endoscopic skull base surgery (ESS). The purpose of this study was to assess the outcomes and complications of a reconstruction technique for immediate CSF leakage repair using multiple onlay grafts following ESS. A total of 230 consecutive patients who underwent skull base reconstruction using multiple onlay grafts with fibrin sealant patch (FSP), hydroxyapatite cement (HAC), and pedicled nasoseptal flap (PNF) for high-flow CSF leakage following ESS at three institutions were enrolled. We retrospectively reviewed the medical and radiological records to analyze the preoperative features and postoperative results. The diagnoses included craniopharyngioma (46.8%), meningioma (34.0%), pituitary adenoma (5.3%), chordoma (1.6%), Rathke's cleft cyst (1.1%) and others (n=21, 11.2%). The trans-planum/tuberculum approach (94.3%) was the most commonly adapted surgical method, followed by the trans-sellar and transclival approaches. The third ventricle was opened in 78 patients (41.5%). Lumbar CSF drainage was not performed postoperatively in any of the patients. Postoperative CSF leakage occurred in four patients (1.7%) due to technical mistakes and were repaired with the same technique. However, postoperative meningitis occurred in 13.5% (n=31) of the patients, but no microorganisms were identified. The median latency to the diagnosis of meningitis was 8 days (range, 2-38). CSF leakage was the unique risk factor for postoperative meningitis (p<0.001). The use of multiple onlay grafts with FSP, HAC, and PNF is a reliable reconstruction technique that provides immediate and complete CSF leakage repair and mucosal grafting on the skull base without the need to harvest autologous tissue or perform postoperative CSF diversion. However, postoperative meningitis should be monitored carefully.