Focused ultrasound-mediated sonochemical internalization: an alternative to light-based therapies

Gonzales, Jonathan; Nair, Rohit Kumar; Madsen, Steen J.; Krasieva, Tatiana B.; Hirschberg, Henry

doi:10.1117/1.jbo.21.7.078002

Cited by 18 publications

(18 citation statements)

References 40 publications

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“…FUS has been explored as a drug delivery platform for treating brain diseases [10] and involves in sonodynamic therapy (SDT) [11]. SDT relies on deep penetration of ultrasound (US) and tumor-specific accumulation of a sonosensitizer, has proved to be an effective, low-cost and safe anti-tumor therapy [12]. Our previous works on SDT have shown its anti-neoplastic effects on various cancers with great potential [13,14].…”

Section: Introductionmentioning

confidence: 99%

Manipulation of Mitophagy by “All-in-One” nanosensitizer augments sonodynamic glioma therapy

et al. 2019

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Limited penetration of chemotherapeutic drugs through the blood brain barrier (BBB), and the increased chemo-resistance of glioma cells due to macroautophagy/autophagy, result in high tumor recurrence and extremely limited survival of glioma patients. Ultrasound-targeted microbubble destruction (UTMD) is a technique of transient and reversible BBB disruption, which greatly facilitates intracerebral drug delivery. In addition, sonodynamic therapy (SDT) based on ultrasound stimulation and a sonosensitizer, can be a safe and noninvasive strategy for treating glioma. We innovatively designed a smart "all-in-one" nanosensitizer platform by incorporating the sonoactive chlorin e6 (Ce6) and an autophagy inhibitor-hydroxychloroquine (HCQ) into angiopep-2 peptide-modified liposomes (designated as ACHL), which integrates multiple diagnostic and therapeutic functions. ACHL selectively accumulated in the brain tumors during the optimal time-window of transient UTMD-mediated BBB opening. The nanosensitizer then responded to a second ultrasonic stimulation, and simultaneously unloaded HCQ and generated ROS in the glioma cells. The sonotherapy triggered apoptosis as well as MAPK/p38-PINK1-PRKN-dependent mitophagy, in which the antioxidant relieved the sonotoxicity and MAPK/p38 activation, while the inhibition of MAPK/p38 attenuated the progression toward mitophagy by compromising redistribution of PRKN. Moreover, HCQ blocking autophagosome degradation, augmented intracellular ROS production and resulted in an oxidative-damage regenerative loop. ACHL-SDT treatment using this construct significantly inhibited the xenograft-tumor growth and prolonged the survival time of tumor-bearing mice, exhibiting an improved therapeutic efficiency. All together, we demonstrated a precision sonotherapy with simultaneous apoptosis induction and mitophagy inhibition, which served as an intelligently strategic sense of working alongside, providing new insights into the theranostics of brain tumors.

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Section: Introductionmentioning

confidence: 99%

Manipulation of Mitophagy by “All-in-One” nanosensitizer augments sonodynamic glioma therapy

et al. 2019

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“…The results shown in Figure 5B, employing this model, demonstrated that SDT potentiated the cytotoxic effects of BLM to a significant degree. This was the case regardless of the sequence of SDT and BLM application, although SDT before drug was more effective [42,45]. This synergistic effect is postulated to be due to endosomal escape, in a similar manner to that seen for light-based PCI [46,47].…”

Section: Review Hirschberg and Madsenmentioning

confidence: 73%

“…In SCI experiments, Gonzales et al studied AlPcS 2a in combination with the anticancer drug, BLM [45]. BLM has had limited clinical use since it must be given in relative high concentrations and has a small therapeutic window.…”

Section: Endosomal Entrapmentmentioning

confidence: 99%

Synergistic Efficacy of Ultrasound, Sonosensitizers and Chemotherapy: A Review

Hirschberg

Madsen

2017

Ther. Deliv.

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Chemotherapeutic agents, either in the form of systemically injected free drug or encapsulated in nanoparticles transport vehicles, must overcome three main obstacles prior to reaching and interacting with their intended target inside tumor cells. Drugs must leave the circulation, overcome the tissue-tumor barrier and penetrate the cell's plasma membrane. Since, many agents enter the cell by endocytosis, they must avoid entrapment and degradation by the intracellular endolysosome complex. Ultrasound has demonstrated potential to enhance the efficacy of chemotherapy by reducing these barriers. The purpose of this review is to highlight the potential of ultrasound in combination with sonosensitizers to enhance the efficacy of chemotherapy by optimizing the anticancer agent's intracellular ability to engage and interact with its target.

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“…Moreover, compared with the Cy5-labeled PK group, the red signal intensity in cells incubated with Cy5-labeled PTPK under US irradiation is stronger (about 2-fold, Figure S6B), and more red fluorescence separates from the green fluorescence (LysoTracker) (lower overlap coefficient, Figure S6C), indicating that PTPK can easily enter cells and escape from the lysosomes into the cytoplasm during US treatment. US can enhance the cellular internalization of nanoparticles, which is known as ''sonochemical internalization,'' since the reactive oxygen species (ROS)-induced lipid peroxidation increases the membrane permeability (Gonzales et al, 2016). Furthermore, the self-assembled nanoparticles can be observed in the lysosomes by Bio-TEM, confirming the in situ self-assembly under US (Figure 2B).…”

Section: In Vitro Cytotoxicity Mechanism and Tissue Penetration Evaluationmentioning

confidence: 59%

Ultrasound-Activated Cascade Effect for Synergistic Orthotopic Pancreatic Cancer Therapy

et al. 2020

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In some malignant tumor, especially for pancreatic tumor, poor solid-tumor penetration of nanotherapeutics impedes their treatment efficacy. Herein, we develop a polymer-peptide conjugate with the deep tissue penetration ability, which undergoes a cascade process under ultrasound (US), including (1) the singlet oxygen 1 O 2 is generated by P18, (2) the thioketal bond is cleaved by the 1 O 2 , (3) the departure of PEG chains leads to the in situ self-assembly, and (4) the resultant self-assembled PK nanoparticles show considerable cellular internalization. Owing to the synergistic effect of US on increasing the membrane permeability, the endocytosis and lysosome escape of PK nanoparticles are further enhanced effectively, resulting in the improved therapeutic efficacy. Thanks to the high tissue-penetrating depth and spatial precision of US, PTPK presents enhanced tumor inhibition in an orthotopic pancreatic tumor model. Therefore, the US-activated cascade effect offers a novel perspective for precision medicine and disease theranostics.

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Focused ultrasound-mediated sonochemical internalization: an alternative to light-based therapies

Cited by 18 publications

References 40 publications

Manipulation of Mitophagy by “All-in-One” nanosensitizer augments sonodynamic glioma therapy

Manipulation of Mitophagy by “All-in-One” nanosensitizer augments sonodynamic glioma therapy

Synergistic Efficacy of Ultrasound, Sonosensitizers and Chemotherapy: A Review

Ultrasound-Activated Cascade Effect for Synergistic Orthotopic Pancreatic Cancer Therapy

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