**16. Promising treatment approaches: Convection enhanced nanoparticle delivery**

**Figure 10.** [45]

**17. Conclusion**

**Author details**

Siddharth K. Joshi1

Brooklyn, New York, USA

Glioblastoma is a deadly and devastating disease that is, as this chapter has made abundantly clear, in need of the development of effective new agents to treat this aggressive tumor. Our understanding of the intrinsic molecular and genetic make of this tumor, although still lacking, has improved rapidly over the past decade and has shed light on current obstacles and is

High Grade Glioma — Standard Approach, Obstacles and Future Directions

http://dx.doi.org/10.5772/58548

25

1 Department of Medicine, New York Methodist Hospital, Brooklyn, New York, USA

2 Department of Medicine-Division of Hematology-Oncology, New York Methodist Hospital,

leading to an array of promising agents on the horizon.

and Richard Zuniga2\*

\*Address all correspondence to: rickzunigaperu@hotmail.com

An utterly novel modality of treatment actively under investigation is the utilization of nanoparticles for the directed delivery of radionuclides into tumor bed. The premise behind this modality is to maximize delivery of radiation therapy to tumor tissue while limiting damage to surrounding normal tissue; external beam radiation is limited to 60 Gy due to toxicity to normal tissue and lack of clinical benefit with higher dose of EBRT. Recently, studies have been published in which radionuclide particles, e.g. 186-Rhenium, are encased in liposomal nanoparticles and injected straight into the GBM tumor bed. In a study published in 2012, Brenner *et al* injected 186-Rhenium liposomes directly into GBM Xenografts trans‐ planted into the brains of rat models. It was found that up to 1850 Gy could be delivered by this method without overt clinical or microscopic evidence of toxicity. Those animals in the experimental arm treated with 186-Rhenium liposomes were found to have a median survival of 126 days vs. a median survival of 49 days for those animals in the control group. Compel‐ lingly, it was found that a large number of the animal subjects that were treated 21 days after tumor grafting were found to have multiple objective indicators of tumor cure (See Figure 10). This included lack of detecting contrast-enhancing tumor on MRI, lack of detecting luminescence by the luminescent molecule embedded in tumor cells, and no tumor cells found on histopathology of resected animal brain tissue. These results suggest that nanoparticle delivery of radioisotopes to the cavities of resected GBM either intra-or postoperatively may have limitless therapeutic potential, particularly when used alongside adjuvant cytotoxic chemotherapy [45].

**Figure 10.** [45]

the human genome, it is postulated that these molecules have influence on as much as ~30% of all gene expression [44]. The expression of one mRNA may be affected by numerous miRNAs; on the same token, one miRNA may affect the expression of multiple mRNAs [44]. The deregulation of miRNA has been pivotally implicated in tumorigenesis; a positive association has been found between those sites in the human genome associated with cancer and areas of miRNA expression [44]. Furthermore, miRNAs have been found to exempli‐ fy both oncogenic and tumor suppressor functions in the tumorigenesis of pancreatic cancer, prostate cancer, thyroid cancer, ovarian cancer, colon cancer, breast cancer, and melano‐ ma. Of recent, the same has also been found in GBM wherein a multitude of miRNAs have been reported to have roles in tumor suppression or oncogenesis. Therapeutic strategies with respect to miRNA aim to augment tumor suppression or antagonize oncogenesis, respectively. In the former case, it is postulated that viral vectors may be utilized to deliver gene therapy to increase the *in situ* expression of tumor suppressive miRNAs. In the latter case, studies pursuing anti-miRNA therapies, e.g. the use of anti-miRNA oligonucleoti‐

**16. Promising treatment approaches: Convection enhanced nanoparticle**

An utterly novel modality of treatment actively under investigation is the utilization of nanoparticles for the directed delivery of radionuclides into tumor bed. The premise behind this modality is to maximize delivery of radiation therapy to tumor tissue while limiting damage to surrounding normal tissue; external beam radiation is limited to 60 Gy due to toxicity to normal tissue and lack of clinical benefit with higher dose of EBRT. Recently, studies have been published in which radionuclide particles, e.g. 186-Rhenium, are encased in liposomal nanoparticles and injected straight into the GBM tumor bed. In a study published in 2012, Brenner *et al* injected 186-Rhenium liposomes directly into GBM Xenografts trans‐ planted into the brains of rat models. It was found that up to 1850 Gy could be delivered by this method without overt clinical or microscopic evidence of toxicity. Those animals in the experimental arm treated with 186-Rhenium liposomes were found to have a median survival of 126 days vs. a median survival of 49 days for those animals in the control group. Compel‐ lingly, it was found that a large number of the animal subjects that were treated 21 days after tumor grafting were found to have multiple objective indicators of tumor cure (See Figure 10). This included lack of detecting contrast-enhancing tumor on MRI, lack of detecting luminescence by the luminescent molecule embedded in tumor cells, and no tumor cells found on histopathology of resected animal brain tissue. These results suggest that nanoparticle delivery of radioisotopes to the cavities of resected GBM either intra-or postoperatively may have limitless therapeutic potential, particularly when used alongside adjuvant cytotoxic

des, are underway for downregulation of oncogenic miRNAs [44].

24 Tumors of the Central Nervous System – Primary and Secondary

**delivery**

chemotherapy [45].
