Ultrasound Contrast Agents and Delivery Systems in Cancer Detection and Therapy

Leon, Al de; Perera, Reshani; Nittayacharn, Pinunta; Cooley, Michaela; Jung, Olive; Exner, Agata A.

doi:10.1016/bs.acr.2018.04.002

Cited by 86 publications

(72 citation statements)

References 91 publications

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“…Although the vascular endothelial gap is expanded in some disease states, such as in tumors, only particles of less than 700 nm in diameter are allowed to pass through . Targeted MBs have a wide range of clinical applications, but because they are larger than 1000 μm, it is difficult for MBs to enter tumor tissue through the vessel wall and specifically bind to tumor cells; in addition, the short in vivo half‐life of MBs results in an insufficient time frame for imaging the target . Therefore, NBs have become a popular topic of recent research on targeted CEUS.…”

Section: Discussionmentioning

confidence: 99%

“…Transrectal ultrasound (US)‐guided biopsy is the reference standard for diagnosing PCa, and the application of an ultrasound contrast agent (UCA) improves the diagnostic sensitivity and accuracy of this method . Microbubbles (MBs), a commonly used UCA, are bubbles larger than 1 μm in diameter and have the advantages of low cost, easy preparation, and excellent contrast . However, because of size limitations, MB‐based imaging is limited to the vasculature, and the MBs usually pool in the blood, rather than circulating as desired .…”

mentioning

confidence: 99%

“…Lipid shells are the most classic component of diagnostic contrast agents and have the advantages of excellent elasticity, easy modification, and biocompatibility . Meanwhile, adding polyethylene glycol (PEG) can delay NB clearance by the reticuloendothelial system . At present, there are few studies on PSMA antibody‐targeted NBs and its US‐targeting development.…”

mentioning

confidence: 99%

“…3 Microbubbles (MBs), a commonly used UCA, are bubbles larger than 1 m in diameter and have the advantages of low cost, easy preparation, and excellent contrast. 4 However, because of size limitations, MB-based imaging is limited to the vasculature, and the MBs usually pool in the blood, rather than circulating as desired. 5 Thus, nanobubbles (NBs) have recently become a hot topic in cancer contrast imaging research.…”

mentioning

confidence: 99%

“…17 Meanwhile, adding polyethylene glycol (PEG) can delay NB clearance by the reticuloendothelial system. 4 At present, there are few studies on PSMA antibody-targeted NBs and its US-targeting development. Differential centrifugation and static stratification are usually used to construct NBs, which are not conducive to the yield and stability of NBs, and their targeting is still lacking.…”

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confidence: 99%

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Optimized Anti–Prostate‐Specific Membrane Antigen Single‐Chain Variable Fragment–Loaded Nanobubbles as a Novel Targeted Ultrasound Contrast Agent for the Diagnosis of Prostate Cancer

Ding

Cao

Qian

et al. 2019

J of Ultrasound Medicine

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Objectives To prepare optimized prostate‐specific membrane antigen (PSMA) single‐chain variable fragment (scFv)–loaded nanobubbles (NBs) as a novel targeted ultrasound (US) contrast agent for diagnosis and treatment of prostate cancer (PCa). Methods Prostate‐specific membrane antigen scFv‐loaded NBs were prepared by membrane hydration and biotin‐streptavidin conjugation. Flow cytometry was used to observe the binding rate of the targeted NBs to PSMA‐expressing cells. Contrast‐enhanced US was used to monitor targeted and nontargeted NBs administered to nude mice with 22RV1, LNCaP, and PC‐3 xenograft tumors. The specific binding ability of the targeted NBs was further examined by fluorescence imaging of tumor cryosections. Results Uniformly sized targeted NBs were successfully prepared (mean ± SD, 485.3 ± 28.4 nm). The NBs showed good stability and bound specifically to LNCaP and 22RV1 cells with high PSMA expression in vitro but did not bind to PC‐3 cells without PSMA expression. The targeted NBs presented good US enhancement, and the results of the in vivo xenograft tumor nude mouse model showed that the peak contrast intensity in LNCaP and 22RV1 cells was significantly higher for the targeted NBs than the nontargeted NBs (P < .05), whereas there was no significant difference in PC‐3 cells. Immunofluorescence results obtained from tumor sections confirmed that the targeted NBs were capable of targeting PSMA‐expressing tumor cells. Conclusions These novel PSMA scFv‐loaded NBs have proven to be an excellent US contrast agent for imaging PSMA‐expressing PCa and have the potential to not only enable efficient and safe molecular imaging but also to serve as a delivery system for targeted PCa therapies.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Optimized Anti–Prostate‐Specific Membrane Antigen Single‐Chain Variable Fragment–Loaded Nanobubbles as a Novel Targeted Ultrasound Contrast Agent for the Diagnosis of Prostate Cancer

Ding

Cao

Qian

et al. 2019

J of Ultrasound Medicine

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Ultrasound‐controlled drug release and drug activation for cancer therapy

et al. 2021

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Traditional chemotherapy suffers from severe toxicity and side effects that limit its maximum application in cancer therapy. To overcome this challenge, an ideal treatment strategy would be to selectively control the release or regulate the activity of drugs to minimize the undesirable toxicity. Recently, ultrasound (US)‐responsive drug delivery systems (DDSs) have attracted significant attention due to the non‐invasiveness, high tissue penetration depth, and spatiotemporal controllability of US. Moreover, the US‐induced mechanical force has been proven to be a robust method to site‐selectively rearrange or cleave bonds in mechanochemistry. This review describes the US‐activated DDSs from the fundamental basics and aims to present a comprehensive summary of the current understanding of US‐responsive DDSs for controlled drug release and drug activation. First, we summarize the typical mechanisms for US‐responsive drug release and drug activation. Second, the main factors affecting the ultrasonic responsiveness of drug carriers are outlined. Furthermore, representative examples of US‐controlled drug release and drug activation are discussed, emphasizing their novelty and design principles. Finally, the challenges and an outlook on this promising therapeutic strategy are discussed.

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Genetic Modulation of Biosynthetic Gas Vesicles for Ultrasound Imaging

Fu,

Wang,

Wang

et al. 2024

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Gas vesicles (GVs) from microorganisms are genetically air‐filled protein nanostructures, and serve as a new class of nanoscale contrast agents for ultrasound imaging. Recently, the genetically encoded GV gene clusters have been heterologously expressed in Escherichia coli, allowing these genetically engineered bacteria to be visualized in vivo in a real‐time manner by ultrasound. However, most of the GV genes remained functionally uncharacterized, which makes it difficult to regulate and modify GVs for broad medical applications. Here, the impact of GV proteins on GV formation is systematically investigated. The results first uncovered that the deletions of GvpR or GvpU resulted in the formation of a larger proportion of small, biconical GVs compared to the full‐length construct, and the deletion of GvpT resulted in a larger portion of large GVs. Meanwhile, the combination of gene deletions has resulted in several genotypes of ultrasmall GVs that span from 50 to 20 nm. Furthermore, the results showed that E. coli carrying the ΔGvpCRTU mutant can produce strong ultrasound contrast signals in mouse liver. In conclusion, the study provides new insights into the roles of GV proteins in GV formation and produce ultrasmall GVs with a wide range of in vivo research.

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Ultrasound Contrast Agents and Delivery Systems in Cancer Detection and Therapy

Cited by 86 publications

References 91 publications

Optimized Anti–Prostate‐Specific Membrane Antigen Single‐Chain Variable Fragment–Loaded Nanobubbles as a Novel Targeted Ultrasound Contrast Agent for the Diagnosis of Prostate Cancer

Optimized Anti–Prostate‐Specific Membrane Antigen Single‐Chain Variable Fragment–Loaded Nanobubbles as a Novel Targeted Ultrasound Contrast Agent for the Diagnosis of Prostate Cancer

Ultrasound‐controlled drug release and drug activation for cancer therapy

Genetic Modulation of Biosynthetic Gas Vesicles for Ultrasound Imaging

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