Abstract
Glioblastoma multiforme (GBM), the most common type of brain cancer, is extremely aggressive and has a dreadful prognosis. GBM comprises 60% of adult brain tumors and the 5 year survival rate of GBM patients is only 4.3%. Standard-of-care treatment includes maximal surgical removal of the tumor in combination with radiation and temozolomide (TMZ) chemotherapy. TMZ is the “gold-standard” chemotherapy for patients suffering from GBM. However, the median survival is only about 12 to 18 months with this protocol. Consequently, there is a critical need to develop new therapeutic options for treatment of GBM. Nanomaterials have unique properties as multifunctional platforms for brain tumor therapy and diagnosis. As one of the nanomaterials, lipid-based nanocarriers are capable of delivering chemotherapeutics and imaging agents to tumor sites by enhancing the permeability of the compound through the blood–brain barrier, which makes them ideal for GBM therapy and imaging. Nanocarriers also can be used for delivery of radiosensitizers to the tumor to enhance the efficacy of the radiation therapy. Previously, high-atomic-number element-containing particles such as gold nanoparticles and liposomes have been used as radiosensitizers. SapC–DOPS, a protein-based liposomal drug comprising the lipid, dioleoylphosphatidylserine (DOPS), and the protein, saposin C (SapC), has been shown to be effective for treatment of a variety of cancers in small animals, including GBM. SapC–DOPS also has the unique ability to be used as a carrier for delivery of radiotheranostic agents for nuclear imaging and radiotherapeutic purposes. These unique properties make tumor-targeting proteo-liposome nanocarriers novel therapeutic and diagnostic alternatives to traditional chemotherapeutics and imaging agents. This article reviews various treatment modalities including nanolipid-based delivery and therapeutic systems used in preclinical and clinical trial settings for GBM treatment and detection.
Highlights
Every year, around 25,000 new patients are diagnosed with primary malignant brain tumors, which have a poor prognosis with an overall 5 year survival rate of 36%, which drops to less than 22% for those over 40 [1]
While cancers originating elsewhere may metastasize to the brain and become secondary tumors, primary brain tumors behave differently, and, while they may migrate within the brain, they rarely spread outside of the central nervous system (CNS) [2,3,4]
Radiation therapy is an essential treatment modality for glioblastoma multiforme (GBM), and technological advances in the field of radiation oncology have contributed to an enhanced radiation effect
Summary
Around 25,000 new patients are diagnosed with primary malignant brain tumors, which have a poor prognosis with an overall 5 year survival rate of 36%, which drops to less than 22% for those over 40 [1]. Secondary brain tumors, which have metastasized to the brain from a tumor in another location (usually lung, breast, colon, kidney, thyroid, or uterine cancers or melanoma) are much more common than primary brain tumors [3,6] These tumors are becoming increasingly more frequent as therapies for primary tumors improve to allow patients to live longer, giving the original cancer more time to spread to the brain. In comparison to old drugs and agents, nanocarriers show great promise for GBM therapy and diagnosis due to their distinctive properties such as size, shape, and surface properties These characteristics can be adjusted to effectively carry and deliver therapeutic and imaging compounds directly and to tumor cells and tissues in a controlled way with fewer side-effects. C (SapC) coupled with dioleoylphosphatidylserine (DOPS) have multiple advantages of carrying imaging agents and chemotherapeutic agent/radiation, as well as being drug by itself, in addition to its ability to cross the BBB for targeting GBM
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