New insights into targeted therapy of glioblastoma using smart nanoparticles (original) (raw)

Theranostic Nanomedicine for Malignant Gliomas

Frontiers in Bioengineering and Biotechnology, 2019

Brain tumors mainly originate from glial cells and are classified as gliomas. Malignant gliomas represent an incurable disease; indeed, after surgery and chemotherapy, recurrence appears within a few months, and mortality has remained high in the last decades. This is mainly due to the heterogeneity of malignant gliomas, indicating that a single therapy is not effective for all patients. In this regard, the advent of theranostic nanomedicine, a combination of imaging and therapeutic agents, represents a strategic tool for the management of malignant brain tumors, allowing for the detection of therapies that are specific to the single patient and avoiding overdosing the non-responders. Here, recent theranostic nanomedicine approaches for glioma therapy are described.

Progress and Viewpoints of Multifunctional Composite Nanomaterials for Glioblastoma Theranostics

Pharmaceutics

The most common malignant tumor of the brain is glioblastoma multiforme (GBM) in adults. Many patients die shortly after diagnosis, and only 6% of patients survive more than 5 years. Moreover, the current average survival of malignant brain tumors is only about 15 months, and the recurrence rate within 2 years is almost 100%. Brain diseases are complicated to treat. The reason for this is that drugs are challenging to deliver to the brain because there is a blood–brain barrier (BBB) protection mechanism in the brain, which only allows water, oxygen, and blood sugar to enter the brain through blood vessels. Other chemicals cannot enter the brain due to their large size or are considered harmful substances. As a result, the efficacy of drugs for treating brain diseases is only about 30%, which cannot satisfy treatment expectations. Therefore, researchers have designed many types of nanoparticles and nanocomposites to fight against the most common malignant tumors in the brain, and the...

Targeted Theranostic Nanoparticles for Brain Tumor Treatment

Pharmaceutics, 2018

The poor prognosis and rapid recurrence of glioblastoma (GB) are associated to its fast-growing process and invasive nature, which make difficult the complete removal of the cancer infiltrated tissues. Additionally, GB heterogeneity within and between patients demands a patient-focused method of treatment. Thus, the implementation of nanotechnology is an attractive approach considering all anatomic issues of GB, since it will potentially improve brain drug distribution, due to the interaction between the blood⁻brain barrier and nanoparticles (NPs). In recent years, theranostic techniques have also been proposed and regarded as promising. NPs are advantageous for this application, due to their respective size, easy surface modification and versatility to integrate multiple functional components in one system. The design of nanoparticles focused on therapeutic and diagnostic applications has increased exponentially for the treatment of cancer. This dual approach helps to understand th...

Smart Nanoformulations for Brain Cancer Theranostics: Challenges and Promises

Cancers

Despite their low prevalence, brain tumors are among the most lethal cancers. They are extremely difficult to diagnose, monitor and treat. Conventional anti-cancer strategies such as radio- and chemotherapy have largely failed, and to date, the development of even a single effective therapeutic strategy against central nervous system (CNS) tumors has remained elusive. There are several factors responsible for this. Brain cancers are a heterogeneous group of diseases with variable origins, biochemical properties and degrees of invasiveness. High-grade gliomas are amongst the most metastatic and invasive cancers, which is another reason for therapeutic failure in their case. Moreover, crossing the blood brain and the blood brain tumor barriers has been a significant hindrance in the development of efficient CNS therapeutics. Cancer nanomedicine, which encompasses the application of nanotechnology for diagnosis, monitoring and therapy of cancers, is a rapidly evolving field of translat...

Theranostic nanoparticles enhance the response of glioblastomas to radiation

Nanotheranostics

Despite considerable progress with our understanding of glioblastoma multiforme (GBM) and the precise delivery of radiotherapy, the prognosis for GBM patients is still unfavorable with tumor recurrence due to radioresistance being a major concern. We recently developed a cross-linked iron oxide nanoparticle conjugated to azademethylcolchicine (CLIO-ICT) to target and eradicate a subpopulation of quiescent cells, glioblastoma initiating cells (GICs), which could be a reason for radioresistance and tumor relapse. The purpose of our study was to investigate if CLIO-ICT has an additive therapeutic effect to enhance the response of GBMs to ionizing radiation. Methods: NSG mice bearing human GBMs and C57BL/6J mice bearing murine GBMs received CLIO-ICT, radiation, or combination treatment. The mice underwent pre-and post-treatment magnetic resonance imaging (MRI) scans, bioluminescence imaging (BLI), and histological analysis. Tumor nanoparticle enhancement, tumor flux, microvessel density, GIC, and apoptosis markers were compared between different groups using a one-way ANOVA and two-tailed Mann-Whitney test. Additional NSG mice underwent survival analyses with Kaplan-Meier curves and a log rank (Mantel-Cox) test. Results: At 2 weeks post-treatment, BLI and MRI scans revealed significant reduction in tumor size for CLIO-ICT plus radiation treated tumors compared to monotherapy or vehicle-treated tumors. Combining CLIO-ICT with radiation therapy significantly decreased microvessel density, decreased GICs, increased caspase-3 expression, and prolonged the survival of GBM-bearing mice. CLIO-ICT delivery to GBM could be monitored with MRI. and was not significantly different before and after radiation. There was no significant caspase-3 expression in normal brain at therapeutic doses of CLIO-ICT administered. Conclusion: Our data shows additive anti-tumor effects of CLIO-ICT nanoparticles in combination with radiotherapy. The combination therapy proposed here could potentially be a clinically translatable strategy for treating GBMs.

Nanotechnology for treatment of glioblastoma multiforme

Journal of Translational Internal Medicine, 2018

Glioblastoma multiforme (GBM), a grade IV astrocytoma as defined by the World Health Organization (WHO) criteria, is the most common primary central nervous system tumor in adults. After treatment with the current standard of care consisting of surgical resection, concurrent temozolomide (TMZ), and radiation, the median survival is only 15 months. The limited and less-effective treatment options for these highly aggressive GBMs call for the development of new techniques and the improvement of existing technologies. Nanotechnology has shown promise in treating this disease, and some nanomaterials have demonstrated the ability to cross the blood-brain barrier (BBB) and remain in GBM tissues. Although the retention of nanoparticles (NPs) in GBM tissue is necessary to elicit an antitumor response, the delivery of the NP needs to be enhanced. Current research in nanotechnology is directed at increasing the active targeting of GBM tissue not only for the aid of chemotherapeutic drug delivery but also for imaging studies. This review is aimed at describing advancements in increasing nanotechnology specificity to GBM tissue.

Nanotechnology Meets Oncology: Nanomaterials in Brain Cancer Research, Diagnosis and Therapy

Materials, 2019

Advances in technology of the past decades led to development of new nanometer scale diagnosis and treatment approaches in cancer medicine leading to establishment of nanooncology. Inorganic and organic nanomaterials have been shown to improve bioimaging techniques and targeted drug delivery systems. Their favorable physico-chemical characteristics, like small sizes, large surface area compared to volume, specific structural characteristics, and possibility to attach different molecules on their surface transform them into excellent transport vehicles able to cross cell and/or tissue barriers, including the blood–brain barrier. The latter is one of the greatest challenges in diagnosis and treatment of brain cancers. Application of nanomaterials can prolong the circulation time of the drugs and contrasting agents in the brain, posing an excellent opportunity for advancing the treatment of the most aggressive form of the brain cancer—glioblastomas. However, possible unwanted side-effe...

Nanoparticle based strategies for the treatment of Glioblastoma

2014

Glioblastoma is the most common and most biologically aggressive primary brain tumour in adults. In spite of tremendous investment into research which has led to the development and application of novel diagnostic and therapeutic measures in the management of glioblastoma, the prognosis is still dismal with median survival time of about 12 – 15 months. Also, the success of most cytotoxic drugs clinically employed in the treatment of glioblastoma is greatly limited by their dose-limiting toxicity which typically manifests as clinically significant reduction in blood cell counts. The aim of this study is to demonstrate that a high dose nanoparticle formulation of the cytotoxic drug lomustine using a self-assembling chitosan amphiphile, quaternary ammonium palmitoyl glycol chitosan would lead to improved survival outcomes without a commensurate increase in toxic effects. The novel nanoparticle based lomustine formulation employed in this study enabled the administration of a lomustine ...

Multimodal targeting of glioma with functionalized nanoparticles

Cancer Cell International

The most common and aggressive primitive intracranial tumor of the central nervous system is the glioma. The blood–brain barrier (BBB) has proven to be a significant obstacle to the effective treatment of glioma. To effectively treat glioma, different ways have been used to cross the BBB to deliver drugs to the brain. Drug delivery through nanocarriers proves to be an effective and non-invasive technique for the treatment of glioma and has great potential in the treatment of glioma. In this review, we will provide an overview of nanocarrier-mediated drug delivery and related glioma therapy. Nanocarrier-mediated drug delivery techniques to cross the BBB (liposomes, micelles, inorganic systems, polymeric nanoparticles, nanogel system, and biomimetic nanoparticles) are explored. Finally, the use of nanotherapeutic approaches in the treatment of glioblastoma including chemotherapy, radiotherapy, photothermal therapy, gene therapy, glioma genome editing, immunotherapy, chimeric antigen r...