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Introduction: We hypothesised that the active targeting of αvβ3 integrin overexpressed in neoangiogenic blood vessels and glioblastoma (GBM) cells combined with magnetic targeting of paclitaxel- and SPIO-loaded PLGA-based nanoparticles could improve accumulation of nanoparticles in the tumour and therefore improve the treatment of GBM. Methods: PTX/SPIO PLGA nanoparticles with or without RGD-grafting were characterised. Their in vitro cellular uptake and cytotoxicity was evaluated by fluorospectroscopy and MTT assay. In vivo safety and anti-tumour efficacy of different targeting strategies were evaluated in orthotopic U87MG tumour model over multiple intravenous injections. Results: The nanoparticles of 250 nm were negatively charged. RGD targeted nanoparticles showed a specific and higher cellular uptake than untargeted nanoparticles by activated U87MG and HUVEC cells. In vitro IC50 of PTX after 48 h was ∼1 ng/mL for all the PTX-loaded nanoparticles. The median survival time of the mice treated with magnetic targeted nanoparticles was higher than the control (saline) mice or mice treated with other evaluated strategies. The 6 doses of PTX did not induce any detectable toxic effects on liver, kidney and heart when compared to Taxol. Conclusion: The magnetic targeting strategy resulted in a better therapeutic effect than the other targeting strategies (passive, active).

Brain tumors are one of the deadly cancers with very high mortality rate and a very difficult to treat. The survival rate for patients suffering from brain and central nervous system cancers was reported to be as low as 36%, with an average survival duration of between 15 and 22 months. Owning to the other underlying complications and severe effects on the physiological functions, the posttreatment survival period is very low. Glioblastoma tumors belong to type IV brain cancers that pose a tremendous socioeconomic burden to the families and the community healthcare system. The conventional treatment of brain cancer consists of surgical resection, radiotherapy, and chemotherapy. However, factors such as systemic toxicity, resistance to treatment, lack of specificity, and presence of blood-brain barrier limit the effectiveness of conventional treatment; hence, there is an incipient need for new therapeutic strategies to overcome these factors. The current chapter aims to present cell- and gene-based therapies, one of the emerging technological trends and advancements in oncology. Cell- and gene-based therapies can offer alternate approaches by fostering either attacking selectively the cancel cells or block the cancer molecular pathways. Individual sections of this chapter elaborate on different types of cell and gene products. A summary of preclinical studies that provided promising results and a few ongoing or concluded clinical trials have been provided. High-level pharmacological effects of these advanced medical products have been presented along with their innate challenges in translating them from bench to bedside.

Introduction Glioblastoma (GBM) therapy is highly challenging, as the tumors are very aggressive due to infiltration into the surrounding normal brain tissue. Even a combination of the available therapeutic regimens may not debulk the tumor completely. GBM tumors are also known for recurrence, resulting in survival rates averaging

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor. Despite available therapeutic options, the prognosis for patients with GBM remains very poor. We hypothesized that the intra-operative injection of a photopolymerizable hydrogel into the tumor resection cavity could sustain the release of the anti-cancer drug paclitaxel (PTX) encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles and prevent GBM recurrence. The tumor was resected 13 days after implantation and a pre-gel solution composed of polyethylene glycol dimethacrylate (PEG-DMA) polymer, a photoinitiator and PTX-loaded PLGA nanoparticles (PTX PLGA-NPs) was injected into the tumor resection cavity. A solid gel filling the whole cavity was formed immediately by photopolymerization using a 400 nm light. PTX in vitro release study showed a burst release (11%) in the first 8 h and a sustained release of 29% over a week. In vitro, U87 MG cells were sensitive to PTX PLGA-NPs with IC50 level of approximately 0.010 μg/mL. The hydrogel was well-tolerated when implanted in the brain of healthy mice for 2 and 4 months. Administration of PTX PLGA-NPs-loaded hydrogel into the resection cavity of GBM orthotopic model lead to more than 50% long-term survival mice (150 days) compared to the control groups (mean survival time 52 days). This significant delay of recurrence is very promising for the post-resection treatment of GBM.

Glioblastoma (GBM) is one of the most aggressive and deadliest central nervous system tumors, and the current standard treatment is surgery followed by radiotherapy with concurrent chemotherapy. Nevertheless, the survival period is notably low. Although ample research has been performed to develop an effective therapeutic strategy for treating GBM, the success of extending patients' survival period and quality of life is limited. This review focuses on the strategies developed to address the challenges associated with drug delivery in GBM, particularly nanomedicine. The first part describes major obstacles to the development of effective GBM treatment strategies. The second part focuses on the conventional chemotherapeutic nanomedicine strategies, their limitations and the novel and advanced strategies of nanomedicine, which could be promising for GBM treatment. We also highlighted the prominence of nanomedicine clinical translation. The near future looks bright following the beginning of clinical translation of nanochemotherapy for GBM.