Repeated blood–brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in patients with recurrent glioblastoma: a phase 1 trial

Sonabend, Adam M.; Gould, Andrew; Amidei, Christina; Ward, Rachel; Schmidt, Karyn A; Zhang, Daniel Y.; Gomez, Cristal; Bebawy, John F.; Liu, Benjamin P.; Bouchoux, Guillaume; Desseaux, Carole; Helenowski, Irene; Lukas, Rimas V.; Dixit, Karan; Kumthekar, Priya; Arrieta, Víctor A.; Lesniak, Maciej S.; Zhang, Hui; Muzzio, Miguel; Canney, Michael; Stupp, Roger

doi:10.1016/s1470-2045(23)00112-2

Cited by 93 publications

(45 citation statements)

References 28 publications

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“…For example, since the CD47/SIRPα axis resides at the infiltrating margin of glioblastoma, including the adjacent microglia population, these regions typically have an intact BBB. As such, therapeutics targeting these axes may need to consider agents that have BBB capabilities or use strategies that can open the BBB, such as low-intensity pulsed ultrasound [80][81][82]. Alternatively, the therapeutic could be deposited into the surgical cavity post resection but would likely be limited by diffusion.…”

Section: Discussionmentioning

confidence: 99%

Glioblastoma Phagocytic Cell Death: Balancing the Opportunities for Therapeutic Manipulation

Du,

Tripathi,

Najem

et al. 2024

Cells

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Macrophages and microglia are professional phagocytes that sense and migrate toward “eat-me” signals. The role of phagocytic cells is to maintain homeostasis by engulfing senescent or apoptotic cells, debris, and abnormally aggregated macromolecules. Usually, dying cells send out “find-me” signals, facilitating the recruitment of phagocytes. Healthy cells can also promote or inhibit the phagocytosis phenomenon of macrophages and microglia by tuning the balance between “eat-me” and “don’t-eat-me” signals at different stages in their lifespan, while the “don’t-eat-me” signals are often hijacked by tumor cells as a mechanism of immune evasion. Using a combination of bioinformatic analysis and spatial profiling, we delineate the balance of the “don’t-eat-me” CD47/SIRPα and “eat-me” CALR/STC1 ligand–receptor interactions to guide therapeutic strategies that are being developed for glioblastoma sequestered in the central nervous system (CNS).

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Section: Discussionmentioning

confidence: 99%

Glioblastoma Phagocytic Cell Death: Balancing the Opportunities for Therapeutic Manipulation

Du,

Tripathi,

Najem

et al. 2024

Cells

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“…The results presented in this work demonstrate that the proper reformulation and sustained delivery of conventional chemotherapeutic molecules, DTXL and PTXL, can dramatically extend the survival of mice bearing orthotopic glioblastomas. This is significant given the revived interest in treating high grade gliomas with poorly brain permeable and highly cytotoxic drugs, as documented by the recent approval of clinical studies where recurrent glioblastoma patients are treated with albumin-bound PTXL upon permeabilization of the blood–brain barrier via multiple, localized ultrasound sources . Despite all of this, the work has some limitations.…”

Section: Study Limitationsmentioning

confidence: 99%

“…This is significant given the revived interest in treating high grade gliomas with poorly brain permeable and highly cytotoxic drugs, as documented by the recent approval of clinical studies where recurrent glioblastoma patients are treated with albumin-bound PTXL upon permeabilization of the blood−brain barrier via multiple, localized ultrasound sources. 34 Despite all of this, the work has some limitations.…”

Section: Study Limitationsmentioning

confidence: 99%

μMESH-Enabled Sustained Delivery of Molecular and Nanoformulated Drugs for Glioblastoma Treatment

et al. 2023

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Modest tissue penetrance, nonuniform distribution, and suboptimal release of drugs limit the potential of intracranial therapies against glioblastoma. Here, a conformable polymeric implant, μMESH, is realized by intercalating a micronetwork of 3 × 5 μm poly(lactic-co-glycolic acid) (PLGA) edges over arrays of 20 × 20 μm polyvinyl alcohol (PVA) pillars for the sustained delivery of potent chemotherapeutic molecules, docetaxel (DTXL) and paclitaxel (PTXL). Four different μMESH configurations were engineered by encapsulating DTXL or PTXL within the PLGA micronetwork and nanoformulated DTXL (nanoDTXL) or PTXL (nanoPTXL) within the PVA microlayer. All four μMESH configurations provided sustained drug release for at least 150 days. However, while a burst release of up to 80% of nanoPTXL/nanoDTXL was documented within the first 4 days, molecular DTXL and PTXL were released more slowly from μMESH. Upon incubation with U87-MG cell spheroids, DTXL-μMESH was associated with the lowest lethal drug dose, followed by nanoDTXL-μMESH, PTXL-μMESH, and nanoPTXL-μMESH. In orthotopic models of glioblastoma, μMESH was peritumorally deposited at 15 days post-cell inoculation and tumor proliferation was monitored via bioluminescence imaging. The overall animal survival increased from ∼30 days of the untreated controls to 75 days for nanoPTXL-μMESH and 90 days for PTXL-μMESH. For the DTXL groups, the overall survival could not be defined as 80% and 60% of the animals treated with DTXL-μMESH and nanoDTXL-μMESH were still alive at 90 days, respectively. These results suggest that the sustained delivery of potent drugs properly encapsulated in conformable polymeric implants could halt the proliferation of aggressive brain tumors.

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“…[ 58 ] This study demonstrated the tolerability and feasibility of delivery of temozolomide and liposomal doxorubicin through the opening of BBB in five glioma patients, providing valuable support for further experiments. Subsequent clinical trials have also shown that LIPUS can temporarily open the BBB, leading to increased brain tissue concentrations of chemotherapeutic drugs such as carboplatin [ 59 ] and albumin‐bound paclitaxel [ 60 ] for the treatment of recurrent GBM. Moreover, FUS‐mediated thermal ablation as well as SDT has been utilized clinically to treat GBM.…”

Section: Ultrasound In Neurological Diseasesmentioning

confidence: 99%

Ultrasound‐Sensitive Intelligent Nanosystems: A Promising Strategy for the Treatment of Neurological Diseases

Pan,

Huang,

Nie

et al. 2023

Advanced Materials

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Neurological diseases are a major global health challenge, affecting hundreds of millions of people worldwide. Ultrasound therapy plays an irreplaceable role in the treatment of neurological diseases due to its non‐invasive, highly focused, and strong tissue penetration capabilities. However, the complexity of brain and nervous system and the safety risks associated with prolonged exposure to ultrasound therapy severely limit the applicability of ultrasound therapy. Ultrasound‐sensitive intelligent nanosystems (USINs) are a novel therapeutic strategy for neurological diseases that bring greater spatiotemporal controllability and improved safety to overcome these challenges. This review provides a detailed overview of therapeutic strategies and clinical advances of ultrasound in neurological diseases, focusing on the potential of USINs‐based ultrasound in the treatment of neurological diseases. Based on the physical and chemical effects induced by ultrasound, rational design of USINs is a prerequisite for improving the efficacy of ultrasound therapy. Recent developments of ultrasound‐sensitive nanocarriers and nanoagents are systemically reviewed. Finally, the challenges and developing prospects of USINs are discussed in depth, with a view to providing useful insights and guidance for efficient ultrasound treatment of neurological diseases.This article is protected by copyright. All rights reserved

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Repeated blood–brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in patients with recurrent glioblastoma: a phase 1 trial

Cited by 93 publications

References 28 publications

Glioblastoma Phagocytic Cell Death: Balancing the Opportunities for Therapeutic Manipulation

Glioblastoma Phagocytic Cell Death: Balancing the Opportunities for Therapeutic Manipulation

μMESH-Enabled Sustained Delivery of Molecular and Nanoformulated Drugs for Glioblastoma Treatment

Ultrasound‐Sensitive Intelligent Nanosystems: A Promising Strategy for the Treatment of Neurological Diseases

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