Ultrasound/microbubble-mediated targeted delivery of anticancer microRNA-loaded nanoparticles to deep tissues in pigs

Ianni, Tommaso Di; Bose, Rajendran J.C.; Sukumar, Uday Kumar; Bachawal, Sunitha V.; Wang, Huaijun; Telichko, Arsenii; Herickhoff, Carl D.; Robinson, Elise; Baker, Sam W.; Vilches-Moure, José G.; Felt, Stephen A.; Gambhir, Sanjiv S.; Paulmurugan, Ramasamy; Dahl, Jeremy

doi:10.1016/j.jconrel.2019.07.024

Cited by 57 publications

(41 citation statements)

References 32 publications

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“…Attaining high tumor volumes usually comes at the expense of high dosages, which can lead to cardiotoxicity among other dangerous side effects ( Singal and Iliskovic, 1998 ). Therefore, achieving higher doxorubicin accumulation in the tumor with the same injected dose is of high value, and this technique could certainly be implemented with other current drugs like sorafenib ( Tan et al, 2019 ) or even nucleic acids ( Scarabel et al, 2017 ; Di Ianni et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Image-Guided Treatment of Primary Liver Cancer in Mice Leads to Vascular Disruption and Increased Drug Penetration

et al. 2020

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Despite advances in interventional procedures and chemotherapeutic drug development, hepatocellular carcinoma (HCC) is still the fourth leading cause of cancer-related deaths worldwide with a <30% 5-year survival rate. This poor prognosis can be attributed to the fact that HCC most commonly occurs in patients with pre-existing liver conditions, rendering many treatment options too aggressive. Patient survival rates could be improved by a more targeted approach. Ultrasound-induced cavitation can provide a means for overcoming traditional barriers defining drug uptake. The goal of this work was to evaluate preclinical efficacy of image-guided, cavitation-enabled drug delivery with a clinical ultrasound scanner. To this end, ultrasound conditions (unique from those used in imaging) were designed and implemented on a Philips EPIQ and S5-1 phased array probe to produced focused ultrasound for cavitation treatment. Sonovue ® microbubbles which are clinically approved as an ultrasound contrast agent were used for both imaging and cavitation treatment. A genetically engineered mouse model was bred and used as a physiologically relevant preclinical analog to human HCC. It was observed that imageguided and targeted microbubble cavitation resulted in selective disruption of the tumor blood flow and enhanced doxorubicin uptake and penetration. Histology results indicate that no gross morphological damage occurred as a result of this process. The combination of these effects may be exploited to treat HCC and other challenging malignancies and could be implemented with currently available ultrasound scanners and reagents.

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Section: Discussionmentioning

confidence: 99%

Image-Guided Treatment of Primary Liver Cancer in Mice Leads to Vascular Disruption and Increased Drug Penetration

et al. 2020

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“… 98 , 116 MB-US mediated delivery of genes and microRNAs in small (mice) and large (pig and dog) animal models of deep-tissue cancers have proven effective. 117 − 119 This may have some applicability for mRNA vaccine delivery via subcutaneous or intramuscular administration for COVID-19. However, the potential for ultrasound-mediated mRNA vaccine delivery has not been explored, and the immune response induced by MB-US alone is yet to be addressed.…”

Section: Current Status Of Sars-cov-2 Vaccine Developmentmentioning

confidence: 99%

SARS-CoV-2 Vaccine Development: An Overview and Perspectives

Liu

Wang

Massoud

et al. 2020

ACS Pharmacol. Transl. Sci.

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Coronavirus disease 2019, abbreviated as COVID-19, is caused by a new strain of coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It started in late December 2019 in Wuhan, China, and by mid-March 2020, the disease had spread globally. As of July 17, 2020, this pandemic virus has infected 13.9 million people and claimed the life of approximately 593 000 people globally, and the numbers continue to climb. An unprecedented effort is underway to develop therapeutic and prophylactic strategies against this disease. Various drugs and vaccines are undergoing rapid development, and some of these are already in phase III clinical trials. Although Russia was the first to release a vaccine by skipping phase III clinical trials, there is no evidence of large-scale clinical trials, and the safety and efficacy of the vaccine are still a concern. Nevertheless, critical lessons can be learned and data garnered for developing promising vaccines against this rapidly emerging virus or other similar pathogens in the future. In this overview, we cover the available information on the various vaccine development initiatives by different companies, the potential strategies adopted for vaccine design, and the challenges and clinical impact expected from these vaccines. We also briefly discuss the possible role of these vaccines and the specific concerns for their use in patients with pre-existing disease conditions such as cardiovascular, lung, kidney, and liver diseases, cancer patients who are receiving immunosuppressive medications, including anticancer chemotherapies, and many other sensitive populations, such as children and the elderly.

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“…Di lanni et al. designed ultrasound and microbubble‐mediated delivery system from PLGA (Figure 12E) NPs loaded with miRNAs (miR‐21 and miR‐10b) in a pig model . Focused ultrasound combined with gas‐filled microbubbles provides a noninvasive way to improve the permeability of the tumor vasculature and increase the delivery efficiency of drug‐loaded NPs to pig liver and kidney.…”

Section: Nanocarriersmentioning

confidence: 99%

Organic Nanocarriers for Delivery and Targeting of Therapeutic Agents for Cancer Treatment

Peng

Bariwal

Kumar

et al. 2020

Advanced Therapeutics

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Nanocarriers have the capability to deliver a variety of drugs to disease sites. Different biological barriers prevent the successful delivery of nanoformulations to target sites, thereby limiting effective therapeutic response. Although numerous efforts have been made to design novel nanocarriers by incorporating various functionalities to get better therapies, most strategies have failed to translate drug delivery systems to the clinic. Impediments such as the incapability to hold drugs stably in nanocarriers during circulation, non‐specific distribution, and inadequate delivery of therapeutic agents to target sites due to complex tumor microenvironment remain a challenge. Herein, different organic polymer and lipid‐based nanocarriers and their encouraging therapeutic effectiveness to treat cancer are discussed. Recent development in multifunctional and stimuli sensitive nanocarriers is also highlighted. Finally, the challenges and innovative strategies to overcome various obstacles and limitations for their successful translation into the clinic are discussed.

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Ultrasound/microbubble-mediated targeted delivery of anticancer microRNA-loaded nanoparticles to deep tissues in pigs

Cited by 57 publications

References 32 publications

Image-Guided Treatment of Primary Liver Cancer in Mice Leads to Vascular Disruption and Increased Drug Penetration

Image-Guided Treatment of Primary Liver Cancer in Mice Leads to Vascular Disruption and Increased Drug Penetration

SARS-CoV-2 Vaccine Development: An Overview and Perspectives

Organic Nanocarriers for Delivery and Targeting of Therapeutic Agents for Cancer Treatment

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