scholarly journals Nanoparticles for Diagnosis and Target Therapy in Pediatric Brain Cancers

Diagnostics ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 173
Author(s):  
Clara Guido ◽  
Clara Baldari ◽  
Gabriele Maiorano ◽  
Angela Mastronuzzi ◽  
Andrea Carai ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Standard Treatment ◽  
Target Therapy ◽  
Tumor Resection ◽  
Pediatric Brain Tumors ◽  
Brain Barrier ◽  
Diagnostic Tools ◽  
Blood Brain ◽  
Cognitive Problems ◽  
Pediatric Brain

Pediatric brain tumors represent the most common types of childhood cancer and novel diagnostic and therapeutic solutions are urgently needed. The gold standard treatment option for brain cancers in children, as in adults, is tumor resection followed by radio- and chemotherapy, but with discouraging therapeutic results. In particular, the last two treatments are often associated to significant neurotoxicity in the developing brain of a child, with resulting disabilities such as cognitive problems, neuroendocrine, and neurosensory dysfunctions/deficits. Nanoparticles have been increasingly and thoroughly investigated as they show great promises as diagnostic tools and vectors for gene/drug therapy for pediatric brain cancer due to their ability to cross the blood–brain barrier. In this review we will discuss the developments of nanoparticle-based strategies as novel precision nanomedicine tools for diagnosis and therapy in pediatric brain cancers, with a particular focus on targeting strategies to overcome the main physiological obstacles that are represented by blood–brain barrier.

Overcoming the Blood-Brain Barrier in Chemotherapy Treatment of Pediatric Brain Tumors

2013 ◽  
Vol 31 (3) ◽  
pp. 531-540 ◽  
Author(s):  
Linfeng Wu ◽  
Xiaoxun Li ◽  
Dileep R. Janagam ◽  
Tao L. Lowe
Keyword(s):  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Pediatric Brain Tumors ◽  
Brain Barrier ◽  
Chemotherapy Treatment ◽  
Blood Brain ◽  
Pediatric Brain

scholarly journals Blood-brain barrier–adapted precision medicine therapy for pediatric brain tumors

2017 ◽  
Vol 188 ◽  
pp. 27.e1-27.e14 ◽  
Author(s):  
Bernard L. Marini ◽  
Lydia L. Benitez ◽  
Andrew H. Zureick ◽  
Ralph Salloum ◽  
Angela C. Gauthier ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Precision Medicine ◽  
Blood Brain Barrier ◽  
Pediatric Brain Tumors ◽  
Brain Barrier ◽  
Blood Brain ◽  
Pediatric Brain

scholarly journals Safety and feasibility of multiple blood-brain barrier disruptions for the treatment of glioblastoma in patients undergoing standard adjuvant chemotherapy

2020 ◽  
pp. 1-9 ◽  
Author(s):  
So Hee Park ◽  
Myung Ji Kim ◽  
Hyun Ho Jung ◽  
Won Seok Chang ◽  
Hyun Seok Choi ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Tumor Resection ◽  
Chemotherapeutic Agents ◽  
Brain Barrier ◽  
Clinical Trial Registration ◽  
Blood Brain ◽  
Chemotherapy Protocol ◽  
Multiple Blood

OBJECTIVEGlioblastoma (GBM) remains fatal due to the blood-brain barrier (BBB), which interferes with the delivery of chemotherapeutic agents. The purpose of this study was to evaluate the safety and feasibility of repeated disruption of the BBB (BBBD) with MR-guided focused ultrasound (MRgFUS) in patients with GBM during standard adjuvant temozolomide (TMZ) chemotherapy.METHODSThis study was a prospective, single-center, single-arm study. BBBD with MRgFUS was performed adjacent to the tumor resection margin on the 1st or 2nd day of the adjuvant TMZ chemotherapy at the same targets for 6 cycles. T2*-weighted/gradient echo (GRE) MRI was performed immediately after every sonication trial, and comprehensive MRI was performed at the completion of all sonication sessions. Radiological, laboratory, and clinical evaluations were performed 2 days before each planned BBBD.RESULTSFrom September 2018, 6 patients underwent 145 BBBD trials at various locations in the brain. The authors observed gadolinium-enhancing spots at the site of BBBD on T1-weighted MRI in 131 trials (90.3%) and 93 trials (64.1%) showed similar spots on T2*-weighted/GRE MRI. When the 2 sequences were combined, BBBD was observed in 134 targets (92.4%). The spots disappeared on follow-up MRI. There were no imaging changes related to BBBD and no clinical adverse effects during the 6 cycles.CONCLUSIONSThis study is the first in which repetitive MRgFUS was performed at the same targets with a standard chemotherapy protocol for malignant brain tumor. BBBD with MRgFUS was performed accurately, repeatedly, and safely. Although a longer follow-up period is needed, this study allows for the possibility of other therapeutic agents that previously could not be used due to the BBB.Clinical trial registration no.: NCT03712293 (clinicaltrials.gov)

scholarly journals Dual labeling with 5-aminolevulinic acid and fluorescein in high-grade glioma surgery with a prototype filter system built into a neurosurgical microscope: technical note

2020 ◽  
Vol 132 (6) ◽  
pp. 1724-1730 ◽  
Author(s):  
Eric Suero Molina ◽  
Christian Ewelt ◽  
Nils Warneke ◽  
Michael Schwake ◽  
Michael Müther ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Aminolevulinic Acid ◽  
Tumor Resection ◽  
Brain Barrier ◽  
Filter System ◽  
Blood Brain ◽  
Tumor Identification ◽  
Barrier Breakdown ◽  
Blood Brain Barrier Breakdown ◽  
Background Enhancement

OBJECTIVERecent efforts to improve visualization of 5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PPIX) fluorescence resulted in a dual-labeling technique, combining it with fluorescein sodium in a prototype setup. Fluorescein identifies regions with blood-brain barrier breakdown in gliomas. However, normally perfused and edematous brain fluoresces unselectively, with strong background enhancement. The aim of this study was to test the feasibility of a novel, integrated filter combination using porphyrins for selective tumor identification and fluorescein for background enhancement.METHODSA microscope with a novel built-in filter system (YB 475) for visualizing both fluorescein and 5-ALA–induced porphyrins was used. Resection limits were identified with the conventional BLUE 400 filter system. Six patients harboring contrast ring-enhancing lesions were analyzed.RESULTSThe complete surgical field could now be illuminated. Fluorescein was helpful for improving background visualization, and enhancing dura, edematous tissue, and cortex. Overlapping regions with both fluorophores harbored merged orange fluorescence. PPIX fluorescence was better visualized, even in areas beyond a normal working distance of approximately 25 cm, where the BLUE 400 filters recognized no or weak fluorescence.CONCLUSIONSThe novel filter system improved general tissue brightness and background visualization, enhancing fluorescence-guided tumor resection. Furthermore, it appears promising from a scientific perspective, enabling the simultaneous and direct observation of areas with blood-brain barrier breakdown and PPIX fluorescence.

A phase 0 first-in-human study using NU-0129: A gold base spherical nucleic acid (SNA) nanoconjugate targeting BCL2L12 in recurrent glioblastoma patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3012-3012 ◽  
Author(s):  
Priya Kumthekar ◽  
Alfred Rademaker ◽  
Caroline Ko ◽  
Karan Dixit ◽  
Margaret A. Schwartz ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Tumor Tissue ◽  
Human Study ◽  
Tumor Resection ◽  
Brain Barrier ◽  
Open Label ◽  
Apoptotic Markers ◽  
Blood Brain ◽  
Phase 0 ◽  
Grade 3

3012 Background: Glioblastoma is a difficult to treat tumor with therapeutics limited by their ability to cross the blood brain barrier. SNAs, i.e., gold nanoparticle cores covalently conjugated with a corona of densely packed, highly oriented siRNA oligonucleotides targeted to the GBM oncogene BCL2L12, represent a novel class of blood-brain and blood-tumor barrier-permeable nanomedicinal conjugates, for suppressing gene expression in the tumors of GBM patients. Methods: This is a single-arm, open-label, “window of opportunity” phase 0 first-in-human trial to determine the safety and bioavailability of a novel nanotherapeutic compound, NU-0129. Enrolled patients were treated with intravenous NU-0129 at the dose of 0.04mg/kg. This treatment dosing was considered microdosing defined as 1/50ththe NOAEL (no observed adverse event level) from non-human primate studies. Treatment was followed by tumor resection 8-48 hours later. Primary outcome patient safety and toxicity was monitored weekly for 3 weeks post-infusion. Secondary objectives included biodistribution of NU0129 in tissue, evaluation of pharmacokinetics of NU0129 and the feasibility of NU0129 administration. Exploratory objectives included Bcl2L12 expression and post treatment apoptotic markers as well as progression free survival and overall survival rates. Results: 8 patients were enrolled, treated and subsequently underwent surgical resection. No significant treatment related toxicities were seen. Severe ( > grade 3) adverse events were observed in two patients: hypophosphatemia (one grade 3, one grade 4) and one patient with grade 3 lymphopenia, all were considered as “possibly related” by treating oncologists. In 6 of the 8 patients sufficient tumor tissue was available for analysis of gold accumulation by ICP-MS (inductively coupled plasma-mass spectrometry), and gold accumulation was seen in the tumor tissue of all 6 of these patients. Conclusions: Macrodosing of the nanotherapeutic NU-0129 was well tolerated in glioblastoma patients with no unexpected adverse effects and showed initial evidence of crossing blood brain barrier. Immunohistochemistry for Bcl2L12 expression, apoptotic markers, and PK studies are pending. The demonstration of gold nanoparticles in the tumor tissue validates this approach for drug delivery. Clinical trial information: NCT03020017.

scholarly journals Cranial Transposition and Revascularization of Autologous Omentum: A Novel Surgical Technique for Bypassing the Blood Brain Barrier after Resection of Recurrent Glioblastoma Multiforme

2021 ◽  
Author(s):  
Omer Doron ◽  
Tom Chen ◽  
Tamika Wong ◽  
Amy Tucker ◽  
Peter Constantino ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Blood Brain Barrier ◽  
Free Flap ◽  
Tumor Resection ◽  
Chemotherapeutic Agents ◽  
Brain Barrier ◽  
External Carotid ◽  
Cerebral Angiogram ◽  
Resection Cavity ◽  
Blood Brain

Abstract Background: Glioblastoma multiforme (GBM) patients continue to suffer a poor prognosis. The blood brain barrier (BBB) comprises one of the obstacles for therapy, creating a barrier that decreases the bioavailability of chemotherapeutic agents in the central nervous system. Previously, a vascularized temporoparietal fascial scalp flap (TPFF) lining the resection cavity was introduced in a trial conducted in our institution, in newly-diagnosed GBM patients in an attempt to bypass the BBB after initial resection. In this paper, we report on a new technique to bypass the BBB after re-resection and potentially to allow tumor antigens to be surveilled by the immune system .Objective: Assess the feasibility of performing a cranial transposition and revascularization of autologous omentum after re-resection of GBM.Methods: Laparoscopically harvested omental free flap was transposed to the resection cavity by a team consisting of neurosurgeons, otolaryngologists, and general surgeons. This was done as part of a single center, single arm, open-label, phase I study.Results: Autologous abdominal omental tissue was harvested laparoscopically on its vascularized pedicle in 2 patients, transposed as a free flap, revascularized using external carotid artery, and carefully laid into the tumor resection cavity. Patients did well postoperatively returning to baseline activities. Graft viability was confirmed by cerebral angiogram. Conclusion: Omental cranial transposition of a laparoscopically harvested, vascularized flap, into the cavity of re-resected GBM patients is feasible and safe in the short term. Further studies are needed to ascertain whether such technique can improve progression free survival and overall survival in these patients.

scholarly journals Blood-brain barrier disruption with low-intensity pulsed ultrasound for the treatment of pediatric brain tumors: a review and perspectives

2020 ◽  
Vol 48 (1) ◽  
pp. E10 ◽  
Author(s):  
Kévin Beccaria ◽  
Michael Canney ◽  
Guillaume Bouchoux ◽  
Stéphanie Puget ◽  
Jacques Grill ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Clinical Trials ◽  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Pediatric Brain Tumors ◽  
Brain Barrier ◽  
Pulsed Ultrasound ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity ◽  
Pediatric Brain

Pediatric brain tumors are the most common solid tumor and the first cause of cancer death in childhood, adolescence, and young adulthood. Current treatments are far from optimal in most of these tumors and the prognosis remains dismal for many of them. One of the main causes of the failure of current medical treatments is in part due to the existence of the blood-brain barrier (BBB), which limits drug delivery to tumors. Opening of the BBB with low-intensity pulsed ultrasound (LIPU) has emerged during the last 2 decades as a promising technique for enhancing drug delivery to the brain. In preclinical models, enhanced delivery of a wide range of therapeutic agents, from low-molecular-weight drugs, to antibodies and immune cells, has been observed as well as tumor control and increased survival. This technique has recently entered clinical trials with extracranial and intracranial devices. The safety and feasibility of this technique has furthermore been shown in patients treated monthly for recurrent glioblastoma receiving carboplatin chemotherapy. In this review, the characteristics of the BBB in the most common pediatric brain tumors are reviewed. Then, principles and mechanisms of BBB disruption with ultrasound (US) are summarized and described at the histological and biological levels. Lastly, preclinical studies that have used US-induced BBB opening in tumor models, recent clinical trials, and the potential use of this technology in pediatrics are provided.

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