Delivery of anti-cancer drugs using microbubble-assisted ultrasound in digestive oncology: from preclinical to clinical studies

Escoffre, Jean‐Michel; Sekkat, Najib; Oujagir, Edward; Bodard, Sylvie; Mousset, Coralie; Presset, Antoine; Chautard, Romain; Ayoub, Jean; Lecomte, Thierry; Bouakaz, Ayache

doi:10.1080/17425247.2022.2061459

Cited by 6 publications

(3 citation statements)

References 63 publications

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“…Microbubble-assisted ultrasound (MB-assisted US) is a noninvasive and targeted drug delivery method that enhances the therapeutic efficacy of anticancer drugs (e.g., chemotherapeutic drugs, oncolytic viruses, kinase inhibitors, nucleic acids, immunotherapeutics, and sonosensitizers) by increasing their intratumoral biodistribution and reducing their off-target effects [ 62 , 63 , 64 , 65 , 66 ]. In vivo, these drugs are either co-injected or injected sequentially with MBs or loaded on or into the MBs before their administration [ 67 ].…”

Section: Resultsmentioning

confidence: 99%

Tumor Spheroids as Model to Design Acoustically Mediated Drug Therapies: A Review

et al. 2023

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Tumor spheroids as well as multicellular tumor spheroids (MCTSs) are promising 3D in vitro tumor models for drug screening, drug design, drug targeting, drug toxicity, and validation of drug delivery methods. These models partly reflect the tridimensional architecture of tumors, their heterogeneity and their microenvironment, which can alter the intratumoral biodistribution, pharmacokinetics, and pharmacodynamics of drugs. The present review first focuses on current spheroid formation methods and then on in vitro investigations exploiting spheroids and MCTS for designing and validating acoustically mediated drug therapies. We discuss the limitations of the current studies and future perspectives. Various spheroid formation methods enable the easy and reproducible generation of spheroids and MCTSs. The development and assessment of acoustically mediated drug therapies have been mainly demonstrated in spheroids made up of tumor cells only. Despite the promising results obtained with these spheroids, the successful evaluation of these therapies will need to be addressed in more relevant 3D vascular MCTS models using MCTS-on-chip platforms. These MTCSs will be generated from patient-derived cancer cells and nontumor cells, such as fibroblasts, adipocytes, and immune cells.

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Section: Resultsmentioning

confidence: 99%

Tumor Spheroids as Model to Design Acoustically Mediated Drug Therapies: A Review

et al. 2023

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“… 10 Many preclinical studies and few clinical studies reported the use of microbubble-assisted ultrasound for the delivery of wide range of therapeutics into primary liver tumors or liver mets. 11 Schisandrin A is a bioactive lignan isolated from the traditional Chinese medicine Fructus schisandrae chinensis . Studies showed that schisandrin A had many pharmacological effects, such as anticancer, hepatoprotection, antiinflammation, which was worthy of further research and development in the future.…”

Section: Introductionmentioning

confidence: 99%

The therapeutic effect of ultrasound targeted destruction of schisandrin A contrast microbubbles on liver cancer and its mechanism

Wang,

Dong

et al. 2024

Radiology and Oncology

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Background The aim of the study was to explore the therapeutic effect of ultrasound targeted destruction of schisandrin A contrast microbubbles on liver cancer and its related mechanism. Materials and methods The Span-PEG microbubbles loaded with schisandrin A were prepared using Span60, NaCl, PEG-1500, and schisandrin A. The loading rate of schisandrin A in Span-PEG composite microbubbles was determined by ultraviolet spectrophotometry method. The Walker-256 cell survival rate of schisandrin A was determined by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay. The content of schisandrin A in the cells was determined by high performance liquid chromatography. Ultrasound imaging was used to evaluate the therapeutic effect in situ. Enzyme linked immunosorbent assay (ELISA) was used to measure the content of inflammatory factors in serum. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of experimental animals in each group. Immunohistochemistry was used to detect the expression of hypoxia inducible factor-1α (HIF-1α), vascular endothlial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR-2) in tumor tissues, and western blot was used to detect the protein expression of phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway in tumor tissues. Results The composite microbubbles were uniform in size, and the particle size distribution was unimodal and stable, which met the requirements of ultrasound contrast agents. The loading rate of schisandrin A in Span-PEG microbubbles was 8.84 ± 0.14%, the encapsulation efficiency was 82.24±1.21%. The IC50 value of schisandrin A was 2.87 μg/mL. The drug + microbubbles + ultrasound (D+M+U) group had the most obvious inhibitory effect on Walker-256 cancer cells, the highest intracellular drug concentration, the largest reduction in tumor volume, the most obvious reduction in serum inflammatory factors, and the most obvious improvement in pathological results. The results of immunohistochemistry showed that HIF-1α, VEGF and VEGFR-2 protein decreased most significantly in D+M+U group (P < 0.01). WB results showed that D+M+U group inhibited the PI3K/AKT/mTOR signaling pathway most significantly (P < 0.01). Conclusions Schisandrin A had an anti-tumor effect, and its mechanism might be related to the inhibition of the PI3K/AKT/mTOR signaling pathway. The schisandrin A microbubbles could promote the intake of schisandrin A in tumor cells after being destroyed at the site of tumor under ultrasound irradiation, thus playing the best anti-tumor effect.

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“…These biological effects lead to enhanced cellular delivery through mechanisms such as drug convection and diffusion through the pores (4-70 kDa) and endocytosis (70-500 kDa) [33][34][35]38]. Following their clinical translation as ultrasound imaging contrast agents, MB formulations have been engineered as ultrasound-responsive carriers to promote and enhance the local delivery and uptake of a wide variety of drugs [8][9][10][11], genes [12][13][14], and cells [15][16][17][18][19][20] for various therapeutic applications. Many of these applications include the delivery of therapeutic agents to treat the brain [19][20][21][22][23], heart [15,[24][25][26], and cancer [27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Targeted Microbubbles for Drug, Gene, and Cell Delivery in Therapy and Immunotherapy

Navarro-Becerra

Borden

2023

Pharmaceutics

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Microbubbles are 1–10 μm diameter gas-filled acoustically-active particles, typically stabilized by a phospholipid monolayer shell. Microbubbles can be engineered through bioconjugation of a ligand, drug and/or cell. Since their inception a few decades ago, several targeted microbubble (tMB) formulations have been developed as ultrasound imaging probes and ultrasound-responsive carriers to promote the local delivery and uptake of a wide variety of drugs, genes, and cells in different therapeutic applications. The aim of this review is to summarize the state-of-the-art of current tMB formulations and their ultrasound-targeted delivery applications. We provide an overview of different carriers used to increase drug loading capacity and different targeting strategies that can be used to enhance local delivery, potentiate therapeutic efficacy, and minimize side effects. Additionally, future directions are proposed to improve the tMB performance in diagnostic and therapeutic applications.

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Delivery of anti-cancer drugs using microbubble-assisted ultrasound in digestive oncology: from preclinical to clinical studies

Cited by 6 publications

References 63 publications

Tumor Spheroids as Model to Design Acoustically Mediated Drug Therapies: A Review

Tumor Spheroids as Model to Design Acoustically Mediated Drug Therapies: A Review

The therapeutic effect of ultrasound targeted destruction of schisandrin A contrast microbubbles on liver cancer and its mechanism

Targeted Microbubbles for Drug, Gene, and Cell Delivery in Therapy and Immunotherapy

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