Explore chapters and articles related to this topic
Carriers for Nucleic Acid Delivery to the Brain
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
As the prevalence and understanding of central nervous system (CNS)-related diseases increases, therapeutic nucleic acids offer great opportunities for their treatment. However, the efficient delivery of nucleic acids to the brain is limited by the blood-brain barrier (BBB). Although viral vectors have been widely used for clinical gene delivery, nonviral nucleic acid delivery systems have lower safety concerns, are easier to manufacture and enable the delivery of all types of nucleic acid cargoes, including chemically modified nucleic acids. This book chapter focuses on nonviral nucleic acid vehicles and the barriers to their delivery to the CNS. Systemic injection and intracranial routes of administration with their specific barriers are discussed. Ligands for receptor- and carrier-mediated transport to the CNS are presented in the context of vehicles and strategies which have been successfully used to overcome delivery barriers in vivo. A guided and transient BBB disruption by sonoporation is discussed as an option to increase brain delivery with minimal side effects. Another focus of this book chapter is the nucleic acid delivery to glioma, one of the most devastating neurological diseases. BBB impairment in late states of glioma provides improved conditions for the delivery of therapeutics. The presented delivery strategies summarise the efforts made to overcome the barriers to nonviral delivery of therapeutic nucleic acids to the CNS and may provide guidelines for the development of novel gene delivery vectors for clinical use.
A Perspective of Ultrasound-Related Micro/Nano Cancer Therapy
Published in Hala Gali-Muhtasib, Racha Chouaib, Nanoparticle Drug Delivery Systems for Cancer Treatment, 2020
Tingting Zheng, Yun Chen, Jiao Peng, Yu Shi, Jun Zhang, Haitao Xiao, Xiangmei Chen, Yongcan Huang, Tao Pei, Zhuxia Zhang, Xue Zhang, Xiaohe Bai, Li Liu, Jinrui Wang
Ultrasound (US) is currently identified not only as a noninvasive diagnosis tool but also as a promising mineral- and/or non-invasive therapeutic tool in hospitals. According to ultrasound adjustability, which includes adjusting frequency, intensity, mode, and waveform, theranostic treatment can be performed in different parameter combinations, of which high-intensity focused ultrasound and low-intensity focused ultrasound are two frequently performed treatments, especially for cancer treatment. Most important traits of cancer theranostic focused ultrasound among others are sonothermal effect, ultrasonic cavitation effect, sonoporation effect, sonodynamic effect, and ultrasound targeted drug delivery. To date, high-intensity focused ultrasound (HIFU) ablation has already been applied clinically; however, low-intensity focused ultrasound (LIFU) targeted cancer therapy is still in preclinical study phase. One of the main challenges for its clinical transition ascribes to its low therapeutic efficiency. Scientists therefore induce hybrid micro-/nanoparticles, which play a role as contrast and/or drug delivery carriers in a microscopic scale. In assistance of hybrid micro-/nanobubbles and correlative smart nanoparticles, ultrasound (e.g., LIFU)-related cancer therapy has been verified as a promising choice with minimal side effects or non-trauma. In this chapter, we will discuss the use of HIFU and LIFU approaches to cancer therapy in combination with micro-/nanoparticles to maximize therapeutic effects.
Safety of diagnostic ultrasound
Published in Peter R Hoskins, Kevin Martin, Abigail Thrush, Diagnostic Ultrasound, 2019
Of course, the existence of an oscillating bubble (i.e. a hazard) does not automatically result in a risk. It is necessary to relate its behaviour with something that could be potentially damaging. When a suspension of cells is exposed to ultrasound and stable cavitation occurs, shear stresses may be sufficient to rupture the cell membranes. Shear is a tearing force, and many biological structures are much more easily damaged by tearing than by compression or tension. Destruction of blood cells in suspension by ultrasound may occur in this way provided that the acoustic pressure is high enough, and this has been shown in vitro for erythrocytes, leucocytes and platelets. In addition, the existence of a second effect, not causing cell destruction, may occur. Gaps can open transiently in the cell membrane during ultrasound exposure, allowing the passage of larger biomolecules such as DNA, an effect known as ‘sonoporation’.
Optimal treatment occasion for ultrasound stimulated microbubbles in promoting gemcitabine delivery to VX2 tumors
Published in Drug Delivery, 2022
Tingting Luo, Luhua Bai, Yi Zhang, Leidan Huang, Hui Li, Shunji Gao, Xiaoxiao Dong, Ningshan Li, Zheng Liu
In Experiment Set 1, the perfusion enhancement effect of tumors stimulated by USMB treatment was repeatedly confirmed as in previous studies (Feng et al., 2021; Li et al., 2021). The PI values of tumor CEUS increased by 11.7% ± 3.6%, the AUC values increased by 28.3% ± 6.4%, and the tumor perfusion area rate increased by 13.4% ± 4.5% in the five experimental groups. No obvious changes in tumor perfusion were observed in the control. USMB treatment was administered using a modified diagnostic US system and lipid-coated MBs. It was remarkably observed that the perfusion enhancement effect could be induced at such low parameters (MI 0.25, PL 5 cycles, and PRF 1.5 kHz). Although the perfusion enhancement effect is supposed to be stimulated concomitantly with sonoporation, it has been ignored in most previous studies (Shapiro et al., 2016). Theoretically, tumor perfusion enhancement may improve the characteristic poor-perfused and hypoxic microenvironment in central solid tumors, which is a major cause of chemotherapeutic resistance (Carmona-Bozo et al., 2021).
Vascular and extracellular matrix remodeling by physical approaches to improve drug delivery at the tumor site
Published in Expert Opinion on Drug Delivery, 2020
Sara Gouarderes, Anne-Françoise Mingotaud, Patricia Vicendo, Laure Gibot
Cavitation of microbubbles following exposure to ultrasounds was shown to alter vascular integrity, allowing the release of circulating molecules. This observation underpinned the extension of sonoporation to be applicable as an anti-cancer treatment. The mechanism is not precisely known but it is hypothesized that the oscillations of cavitating microbubbles generate mechanical forces on the vessel wall and a concomitant permeability and molecule transport improvements [135]. When applied in vivo, microbubbles exposed to low-frequency ultrasound have been shown to cause rupture of microvessels accompanied with extravasation of red blood cells [136]. Stable cavitation temporarily increases the gap-junction distance between vascular endothelial cells, cause vessel distention and invagination [137], as well as separation of the endothelium from the vessel wall [138]. All these events lead to loss of vascular integrity and increase the permeability to circulating drugs or nanotherapeutics.
Ultrasonically controlled estrone-modified liposomes for estrogen-positive breast cancer therapy
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Najla M. Salkho, Vinod Paul, Pierre Kawak, Rute F. Vitor, Ana M. Martins, Mohammad Al Sayah, Ghaleb A. Husseini
Several mechanisms could play a part in causing the US-induced release and uptake observed. Many studies showed that US can enhance the permeability of cell membranes through a phenomenon known as sonoporation, which results from cavitation events. Sonoporation can be reversible or irreversible. In reversible sonoporation, the cell can heal the damage in the membrane caused by the formation of micropores as a result of bubble implosion upon US exposure [79–81]. Hence, sonoporation improves the uptake of large molecules by human cells. A study conducted by Jelenc et al. [81] investigated the effect of LFUS on cell morphology and uptake. In the study, mouse melanoma B16-F1 cells incubated with propidium iodide (PI) were exposed to 29.6 kHz US at an intensity of 21.1 W/cm2 for 300 s. Cells with intact membrane morphology were detected by a fluorescence microscope, and some showed a significant level of fluorescence due to PI uptake. Normally, PI cannot penetrate through cell membrane unless it is damaged, thus the study proved the enhanced permeability of cell membranes caused by reversible sonoporation. Fan et al. [82,83] conducted similar studies in sonoporation, and they were able to control and quantify the pore size and the resealing rates of pores of a plasma membrane (HEK-293) targeted by microbubbles and upon exposure to ultrasound. In another study, Liu et al. [84] proved reversible sonoporation of erythrocytes once exposed to US at 24 kHz.