Topics

Oncoprotein Inhibitor Rigosertib Loaded in ApoE-Targeted Smart Polymersomes Reveals High Safety and Potency against Human Glioblastoma in Mice.

08:00 EDT 12th July 2019 | BioPortfolio

Summary of "Oncoprotein Inhibitor Rigosertib Loaded in ApoE-Targeted Smart Polymersomes Reveals High Safety and Potency against Human Glioblastoma in Mice."

The unbiased cytotoxicity and blood-brain barrier (BBB) impermeability render common chemotherapeutics nonviable for treating glioblastoma (GBM) patients. Although rigosertib (RGS), a RAS effector protein inhibitor, has shown low toxicity to healthy cells and high efficacy toward various cancer cells by inactivating PI3K-Akt, it hardly overcomes the BBB barricade. Here, we report that RGS loaded in apolipoprotein E derived peptide (ApoE)-targeted chimaeric polymersomes (ApoE-CP) is safe and highly potent against human GBM in vivo. ApoE-CP exhibited stable loading of RGS in its lumen, giving RGS nanoformulations (ApoE-CP-RGS) with a size of 60 nm and reduction-triggered drug release behavior. Notably, ApoE-CP-RGS induction markedly enhanced the G2/M cell cycle arrest and inhibitory effect in U-87 MG glioblastoma cells compared with the nontargeted CP-RGS and free RGS. The therapeutic outcomes in orthotopic U-87 MG GBM models demonstrated that ApoE-CP-RGS brought about effective GBM inhibition, greatly prolonged survival time, and depleted adverse effects. Rigosertib formulated in ApoE-targeted chimaeric polymersomes has emerged as a novel, highly specific, efficacious, and nontoxic treatment for glioblastoma.

Affiliation

Journal Details

This article was published in the following journal.

Name: Molecular pharmaceutics
ISSN: 1543-8392
Pages:

Links

DeepDyve research library

PubMed Articles [8510 Associated PubMed Articles listed on BioPortfolio]

Polymersomes: Preparation and Characterization.

Polymersomes, also called polymeric vesicles, are self-assembled by amphiphilic copolymers. Due to their unique characters, polymersomes are attracting more and more interest as an important class of ...

Generation of a set of isogenic, gene-edited iPSC lines homozygous for all main APOE variants and an APOE knock-out line.

Alzheimer's disease (AD) is the most frequent neurodegenerative disease amongst the elderly. The SNPs rs429358 and rs7412 in the APOE gene are the most common risk factor for sporadic AD, and there ar...

The Absorption of Apolipoprotein E by Damaged Neurons Facilitates the Neuronal Repair.

Traumatic brain injury (TBI) is one of the common diseases diagnosed in the department of neurosurgery. Apolipoprotein E (apoE) can improve prognosis of TBI. In this study, we aimed to explore the eff...

Smart and dual-targeted BSA nanomedicine with controllable release by high autolysosome levels.

Targeting modifications and smart responsiveness of nanomedicines can enable anticancer drugs to be selectively delivered to and controllably released in tumour cells or tissues, which can reduce the ...

Peripheral Versus Central Nervous System APOE in Alzheimer's Disease:Interplay across the Blood-Brain Barrier.

The apolipoprotein E (APOE) ε4 allele has been demonstrated as the preeminent genetic risk factor for late onset Alzheimer's disease (AD), which comprises greater than 90% of all AD cases. The discov...

Clinical Trials [4686 Associated Clinical Trials listed on BioPortfolio]

Oral Rigosertib for Squamous Cell Carcinoma

The primary objective of this study is to determine if tumors in patients with papillomavirus (HPV) positive or negative squamous cell carcinoma (SCC) that no longer responds to standard t...

Efficacy and Safety of Oral Rigosertib in Transfusion-dependent, Low or Int-1 or Trisomy 8 Int-2 Myelodysplastic Syndrome

The primary objectives of this study are to determine if rigosertib sodium, given orally in the form of soft gel capsules, is safe and is associated with a reduction in the number of blood...

Rigosertib for RDEB-SCC

Epidermolysis bullosa (EB) is a heritable skin disease characterized by marked fragility of epithelialized tissue with blistering in skin and mucous membranes following the slightest mecha...

Controlled Study of Rigosertib Versus Physician's Choice of Treatment in MDS Patients After Failure of an HMA

The primary objective of this study is to compare the overall survival (OS) of patients receiving intravenous (IV) rigosertib to the OS of patients receiving the physician's choice of trea...

Network-Level Mechanisms for Preclinical Alzheimer's Disease Development

The purpose of this project is to test the hypothesis that a low dose of levetiracetam can reduce abnormal hyperfunctional activity in the hippocampus in normal, healthy adults who are APO...

Medical and Biotech [MESH] Definitions

Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (IMMUNOTOXINS) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (see RADIOTHERAPY).

Hand-sized cards with built-in computer chips used for accessing, storing, and protecting patients' medical information.

SMOKING by use of a narrow conveying tube which feeds from an open cavity where smoked product is loaded and burned.

Use of a device (film badge) for measuring exposure of individuals to radiation. It is usually made of metal, plastic, or paper and loaded with one or more pieces of x-ray film.

Strains of mice that contain genetic disruptions (knockout) of APOLIPOPROTEINS E genes. They are used as models for ATHEROSCLEROSIS research.

Quick Search


DeepDyve research library

Relevant Topics

Nutrition
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Cancer
  Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...


Searches Linking to this Article