Current advances in ultrasound-combined nanobubbles for cancer-targeted therapy: a review of the current status and future perspectives

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Abstract

The non-specific distribution, non-selectivity towards cancerous cells, and adverse off-target side effects of anticancer drugs and other therapeutic molecules lead to their inferior clinical efficacy. Accordingly, ultrasound-based targeted delivery of therapeutic molecules loaded in smart nanocarriers is currently gaining wider acceptance for the treatment and management of cancer. Nanobubbles (NBs) are nanosize carriers, which are currently used as effective drug/gene delivery systems because they can deliver drugs/genes selectively to target sites. Thus, combining the applications of ultrasound with NBs has recently demonstrated increased localization of anticancer molecules in tumor tissues with triggered release behavior. Consequently, an effective therapeutic concentration of drugs/genes is achieved in target tumor tissues with ultimately increased therapeutic efficacy and minimal side-effects on other non-cancerous tissues. This review illustrates present developments in the field of ultrasound-nanobubble combined strategies for targeted cancer treatment. The first part of this review discusses the composition and the formulation parameters of NBs. Next, we illustrate the interactions and biological effects of combining NBs and ultrasound. Subsequently, we explain the potential of NBs combined with US for targeted cancer therapeutics. Finally, the present and future directions for the improvement of current methods are proposed.

Abstract

NBs combined with ultrasound demonstrated the ability to enhance the targeting of anticancer agents and improve the efficacy.

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Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2017)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics. In 2017, 1,688,780 new cancer cases and 600,920 cancer deaths are projected to occur in the United States. For all sites combined, the cancer incidence rate is 20% higher in men than in women, while the cancer death rate is 40% higher. However, sex disparities vary by cancer type. For example, thyroid cancer incidence rates are 3-fold higher in women than in men (21 vs 7 per 100,000 population), despite equivalent death rates (0.5 per 100,000 population), largely reflecting sex differences in the "epidemic of diagnosis." Over the past decade of available data, the overall cancer incidence rate (2004-2013) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2005-2014) declined by about 1.5% annually in both men and women. From 1991 to 2014, the overall cancer death rate dropped 25%, translating to approximately 2,143,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the cancer death rate was 15% higher in blacks than in whites in 2014, increasing access to care as a result of the Patient Protection and Affordable Care Act may expedite the narrowing racial gap; from 2010 to 2015, the proportion of blacks who were uninsured halved, from 21% to 11%, as it did for Hispanics (31% to 16%). Gains in coverage for traditionally underserved Americans will facilitate the broader application of existing cancer control knowledge across every segment of the population. CA Cancer J Clin 2017;67:7-30. © 2017 American Cancer Society.

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Nanotechnology has the potential to revolutionize cancer diagnosis and therapy. Advances in protein engineering and materials science have contributed to novel nanoscale targeting approaches that may bring new hope to cancer patients. Several therapeutic nanocarriers have been approved for clinical use. However, to date, there are only a few clinically approved nanocarriers that incorporate molecules to selectively bind and target cancer cells. This review examines some of the approved formulations and discusses the challenges in translating basic research to the clinic. We detail the arsenal of nanocarriers and molecules available for selective tumour targeting, and emphasize the challenges in cancer treatment.

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In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus

Raimunda Azevedo, Jorge R. de Sousa, Marialva Araujo … (2018)

Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.

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Author and article information

Journal

Journal ID (nlm-ta): RSC Adv

Journal ID (iso-abbrev): RSC Adv

Journal ID (publisher-id): RA

Journal ID (coden): RSCACL

Title: RSC Advances

Publisher: The Royal Society of Chemistry

ISSN (Electronic): 2046-2069

Publication date (Electronic, pub): 6 April 2021

Publication date (Electronic, collection): 29 March 2021

Publication date PMC-release: 6 April 2021

Volume: 11

Issue: 21

Pages: 12915-12928

Affiliations

[a] Department of Ultrasound Diagnosis, Lanzhou University Second Hospital Lanzhou 730030 Gansu Province China ery_nief@ 123456lzu.edu.cn +86-0931-2336818

[b] Department of Pain, Lanzhou University Second Hospital Lanzhou 730030 Gansu Province China

[c] Department of Orthopedics, Lanzhou University Second Hospital Lanzhou 730030 Gansu Province China

[d] Department of Ultrasound Diagnosis, Gansu Provincial Maternity and Child-Care Hospital Lanzhou 730030 Gansu Province China

[e] Department of Pneumology, Lanzhou University Second Hospital Lanzhou 730030 Gansu Province China

[f] Department of Emergency, Lanzhou University Second Hospital Lanzhou 730030 Gansu Province China

Author information

Chunhong Su https://orcid.org/0000-0002-5176-9878

Fang Nie https://orcid.org/0000-0001-9725-1743

Article

Publisher ID: d0ra08727k

DOI: 10.1039/d0ra08727k

PMC ID: 8697319

PubMed ID: 35423829

SO-VID: 819a7f1c-f32e-452a-a7b5-471918219b2b

History

Date received : 13 October 2020

Date accepted : 16 March 2021

Page count

Pages: 14

Funding

Funded by: National Natural Science Foundation of China, doi 10.13039/501100001809;

Award ID: 81873898

Award ID: 81960316

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Current advances in ultrasound-combined nanobubbles for cancer-targeted therapy: a review of the current status and future perspectives

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Most cited references 119

Cancer Statistics, 2017.

Nanocarriers as an emerging platform for cancer therapy.

In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus

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