Cavitation-modulated inflammatory response following focused ultrasound blood-brain barrier opening

Ji, Robin; Karakatsani, Maria Eleni; Burgess, Mark; Smith, Morgan; Murillo, Maria F.; Konofagou, Elisa E.

doi:10.1016/j.jconrel.2021.07.042

Cited by 67 publications

(52 citation statements)

References 63 publications

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“…Inflammation was temporary in this report, lasting up to 24 h; however, a follow-up study using a large microbubble dose, in addition to a high-pressure amplitude, triggered elevated immunoreactivity lasting 7 weeks coupled with glial scar formation [261]. FUS-induced inflammation can be optimised to limit the severity of parenchymal sterile inflammation [262][263][264]; however, the safety of even these conditions must be thoroughly assessed, with particular attention paid to the long-term effects of repeated FUS sessions.…”

Section: Bbb Modulation and Sterile Inflammationmentioning

confidence: 73%

Modulating the Blood–Brain Barrier: A Comprehensive Review

2021

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The highly secure blood–brain barrier (BBB) restricts drug access to the brain, limiting the molecular toolkit for treating central nervous system (CNS) diseases to small, lipophilic drugs. Development of a safe and effective BBB modulator would revolutionise the treatment of CNS diseases and future drug development in the area. Naturally, the field has garnered a great deal of attention, leading to a vast and diverse range of BBB modulators. In this review, we summarise and compare the various classes of BBB modulators developed over the last five decades—their recent advancements, advantages and disadvantages, while providing some insight into their future as BBB modulators.

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Section: Bbb Modulation and Sterile Inflammationmentioning

confidence: 73%

Modulating the Blood–Brain Barrier: A Comprehensive Review

2021

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“…A follow-on preclinical study determined that immunostimulation occurred if the ultrasound’s pressure amplitude was increased above those used in the clinical trial [ 6 ]. Cavitation-mediated inflammation has also been observed in other preclinical studies using neuronavigation [ 156 ]. A third clinically investigated methodology uses surgically implanted ultrasound transducers [ 157 , 158 , 159 ].…”

Section: Strategies To Enhance Immunotherapy’s Effectivenessmentioning

confidence: 77%

Advances in Immunotherapy for the Treatment of Adult Glioblastoma: Overcoming Chemical and Physical Barriers

Lechpammer

Rao

Shah

et al. 2022

Cancers

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Glioblastoma, or glioblastoma multiforme (GBM, WHO Grade IV), is a highly aggressive adult glioma. Despite extensive efforts to improve treatment, the current standard-of-care (SOC) regimen, which consists of maximal resection, radiotherapy, and temozolomide (TMZ), achieves only a 12–15 month survival. The clinical improvements achieved through immunotherapy in several extracranial solid tumors, including non-small-cell lung cancer, melanoma, and non-Hodgkin lymphoma, inspired investigations to pursue various immunotherapeutic interventions in adult glioblastoma patients. Despite some encouraging reports from preclinical and early-stage clinical trials, none of the tested agents have been convincing in Phase III clinical trials. One, but not the only, factor that is accountable for the slow progress is the blood–brain barrier, which prevents most antitumor drugs from reaching the target in appreciable amounts. Herein, we review the current state of immunotherapy in glioblastoma and discuss the significant challenges that prevent advancement. We also provide thoughts on steps that may be taken to remediate these challenges, including the application of ultrasound technologies.

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“… 63–65 Thus, in our studies, the mechanism of the favorable prognosis may be attributed to the fact that combinatorial FUS/chemo therapy can reduce EMT with assistance of SDT and DOX through the cavitation effects, thermal effects and biological effects of FUS. 66 , 67 However, the molecular mechanism remains unclear, which is worth more intense researches in future.…”

Section: Resultsmentioning

confidence: 99%

Multifunctional Theranostic Nanoparticles for Enhanced Tumor Targeted Imaging and Synergistic FUS/Chemotherapy on Murine 4T1 Breast Cancer Cell

Kang¹,

Yang²,

Xu³

et al. 2022

IJN

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Purpose Triple negative breast cancer (TNBC) is challenging for effective remission due to its very aggressive, extremely metastatic and resistant to conventional chemotherapy. Herein, a multifunctional theranostic nanoparticle was fabricated to enhance tumor targeted imaging and promote focused ultrasound (FUS) ablation and chemotherapy and sonodynamic therapy (SDT). A multi-modal synergistic therapy can improve the therapeutic efficacy and prognosis of TNBC. Methods AS1411 aptamer modified PEG@PLGA nanoparticles encapsulated with perfluorohexane (PFH) and anti-cancer drug doxorubicin (DOX) were constructed (AS1411-DOX/PFH-PEG@PLGA) to enhance tumor targeted imaging to guide ablation and synergistic effect of FUS/chemotherapy. FUS was utilized to trigger the co-release of doxorubicin and simultaneously PFH phase transition and activate DOX for SDT effect. The physicochemical, phase-changeable imaging capability, biosafety of nanoparticles and multi-mode synergistic effects on growth of TNBC were thoroughly evaluated in vivo and in vitro. Results The synthesized AS1411-DOX/PFH-PEG@PLGA (A-DPPs) nanoparticles are uniformly round with an average diameter of 306.03 ± 5.35 nm and the zeta potential of −4.05 ± 0.13 mV, displaying high biosafety and FUS-responsive drug release in vitro and in vivo. AS1411 modified NPs specifically bind to 4T1 cells and elevate the ultrasound contrast agent (UCA) image contrast intensity via PFH phase-transition after FUS exposure. Moreover, the combined treatment of A-DPPs nanoparticles with FUS exhibited significantly higher apoptosis rate, stronger inhibitory effect on 4T1 cell invasion in vitro, induced more reactive oxygen species (ROS), and enhanced anti-tumor effect compared to a single therapy (p < 0.05). Additionally, the joint strategy resulted in more intense cavitation effect and larger ablated areas and reduced energy efficiency factor (EEF) both in vitro and in vivo. Conclusion The multifunctional AS1411-DOX/PFH-PEG@PLGA nanoparticles can perform as a marvelous synergistic agent for enhanced FUS/chemotherapy, promote real-time contrast enhanced US imaging and improve the therapeutic efficacy and prognosis of TNBC.

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Cavitation-modulated inflammatory response following focused ultrasound blood-brain barrier opening

Cited by 67 publications

References 63 publications

Modulating the Blood–Brain Barrier: A Comprehensive Review

Modulating the Blood–Brain Barrier: A Comprehensive Review

Advances in Immunotherapy for the Treatment of Adult Glioblastoma: Overcoming Chemical and Physical Barriers

Multifunctional Theranostic Nanoparticles for Enhanced Tumor Targeted Imaging and Synergistic FUS/Chemotherapy on Murine 4T1 Breast Cancer Cell

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