Crosslinked self-assembled nanoparticles for chemo-sonodynamic combination therapy favoring antitumor, antimetastasis management and immune responses.
TL;DR: This work designed a novel redox/enzyme/ultrasound responsive chondroitin sulfate‐chlorin e6‐lipoic acid nanoplatform loading docetaxel, combining SDT and chemotherapy, for antiproliferation and antimetastasis of melanoma.
About: This article is published in Journal of Controlled Release.The article was published on 2018-11-28. It has received 95 citations till now. The article focuses on the topics: Sonodynamic therapy & Drug delivery.
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TL;DR: This review article highlights the recent advances in SDT in terms of sonosensitizers and their formulations and anticancer therapeutic efficacy and the potential ofSDT in combination with other modalities to address unmet needs in precision medicine.
Abstract: Phototherapy, including photodynamic therapy and photothermal therapy, has the potential to treat several types of cancer. However, to be an effective anticancer treatment, it has to overcome limitations, such as low penetration depth, low target specificity, and resistance conferred by the local tumor microenvironment. As a non-invasive technique, low-intensity ultrasound has been widely used in clinical diagnosis as it exhibits deeper penetration into the body compared to light. Recently, sonodynamic therapy (SDT), a combination of low-intensity ultrasound with a chemotherapeutic agent (sonosensitizer), has been explored as a promising alternative for cancer therapy. As all known cancer treatments such as chemotherapy, photodynamic therapy, photothermal therapy, immunotherapy, and drug delivery have been advanced independently enough to complement others substantially, the combination of these therapeutic modalities with SDT is opportune. This review article highlights the recent advances in SDT in terms of sonosensitizers and their formulations and anticancer therapeutic efficacy. Also discussed is the potential of SDT in combination with other modalities to address unmet needs in precision medicine.
426 citations
TL;DR: The design principles in achieving synergistic therapeutic effects based on nanomaterial engineering methods are highlighted and the ultimate goals are to stimulate the design of better‐quality combined sonodynamic treatment schemes and provide innovative ideas for the perspectives of SDT in promoting its future transformation to clinical application.
Abstract: Ultrasound (US)-triggered sonodynamic therapy (SDT), as a promising noninvasive therapeutic modality, has received ever-increasing attention in recent years. Its specialized chemical agents, named sonosensitizers, are activated by low-intensity US to produce lethal reactive oxygen species (ROS) for oncotherapy. Compared with phototherapeutic strategies, SDT provides many noteworthy opportunities and benefits, such as deeper penetration depth, absence of phototoxicity, and fewer side effects. Nevertheless, previous studies have also demonstrated its intrinsic limitations. Thanks to the facile engineering nature of nanotechnology, numerous novel nanoplatforms are being applied in this emerging field to tackle these intrinsic barriers and achieve continuous innovations. In particular, the combination of SDT with other treatment strategies has demonstrated a superior efficacy in improving anticancer activity relative to that of monotherapies alone. Therefore, it is necessary to summarize the nanomaterial-assisted combinational sonodynamic cancer therapy applications. Herein, the design principles in achieving synergistic therapeutic effects based on nanomaterial engineering methods are highlighted. The ultimate goals are to stimulate the design of better-quality combined sonodynamic treatment schemes and provide innovative ideas for the perspectives of SDT in promoting its future transformation to clinical application.
248 citations
TL;DR: This review provides summary, discussion and inspiration of the types of novel sonosensitizers developed in the last few years and outlines their specific designs and the potential challenges.
Abstract: Modalities for photo-triggered anticancer therapy are usually limited by their low penetrative depth. Sonotheranostics especially sonodynamic therapy (SDT), which is different from photodynamic therapy (PDT) by the use of highly penetrating acoustic waves to activate a class of sound-responsive materials called sonosensitizers, has gained significant interest in recent years. The effect of SDT is closely related to the structural and physicochemical properties of the sonosensitizers, which has led to the development of new sound-activated materials as sonosensitizers for various biomedical applications. This Review provides a summary and discussion of the types of novel sonosensitizers developed in the last few years and outlines their specific designs and the potential challenges. The applications of sonosensitizers with various functions such as for imaging and drug delivery as well as in combination with other treatment modalities would provide new strategies for disease therapy.
206 citations
TL;DR: Various newly developed strategies to improve the efficacy of SDT through the use of sonosensitizers based on the mechanisms ofSDT are summarized, providing a theoretical basis for the development of SDt in the future.
Abstract: Sonodynamic therapy (SDT) is a new therapeutic method, which can kill malignant tumors by using sonosensitizers and low intensity ultrasound (US) simultaneously. Compared with photo-triggered therapy, SDT exhibits lots of benefits and merits, including high accuracy, deeper tissue penetration, good patient compliance, and fewer side effects. US can penetrate the deep tissues and focus on the tumor areas, thereby activating sonosensitizers, which offers the possibility of non-invasively eradicating solid tumors in a targeted manner. However, the hypoxic tumor microenvironment (TME) and the low quantum yield of sonosensitizers limit the treatment efficiency of SDT. Therefore, it is crucial to improve the sonodynamic effect. In this minireview, we briefly introduce the possible mechanisms of SDT, including the production of reactive oxygen species (ROS), cavitation effect, and hyperthermia destruction. Then we summarize various newly developed strategies to improve the efficacy of SDT through the use of sonosensitizers based on the mechanisms of SDT, providing a theoretical basis for the development of SDT in the future. The strategies to improve the therapeutic efficiency of SDT mainly include: (1) improvement of hypoxia; (2) enhancement of the cavitation effect; (3) consumption of reducing substances (e.g., glutathione, GSH); (4) combination with hypoxia-activated chemotherapeutic drugs; and (5) combination with immunotherapy. In addition, we also focus on the potential strategies of combining SDT with other therapies, and discuss the challenges and limitations of SDT in future clinical applications.
144 citations
TL;DR: As a promising treatment, the application of immunotherapy in tumor metastasis treatment is introduced, and strategies that stimulating immune response are reviewed, including chemotherapy, photothermal therapy, photodynamic Therapy, ferroptosis, sonodynamic therapy, and nanovaccines.
119 citations
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TL;DR: It is argued that redox biology, rather than oxidative stress, underlies physiological and pathological conditions.
4,297 citations
TL;DR: These factors have been shown to substantially affect the biodistribution and blood circulation half-life of circulating nanoparticles by reducing the level of nonspecific uptake, delaying opsonization, and increasing the extent of tissue specific accumulation.
Abstract: Nanoparticle (NP) drug delivery systems (5−250 nm) have the potential to improve current disease therapies because of their ability to overcome multiple biological barriers and releasing a therapeutic load in the optimal dosage range. Rapid clearance of circulating nanoparticles during systemic delivery is a critical issue for these systems and has made it necessary to understand the factors affecting particle biodistribution and blood circulation half-life. In this review, we discuss the factors which can influence nanoparticle blood residence time and organ specific accumulation. These factors include interactions with biological barriers and tunable nanoparticle parameters, such as composition, size, core properties, surface modifications (pegylation and surface charge), and finally, targeting ligand functionalization. All these factors have been shown to substantially affect the biodistribution and blood circulation half-life of circulating nanoparticles by reducing the level of nonspecific uptake, de...
3,009 citations
Journal Article•
TL;DR: In this article, the authors discuss the factors which can influence nanoparticle blood residence time and organ specific accumulation, including interactions with biological barriers and tunable nanoparticle parameters, such as composition, size, core properties, surface modifications (pegylation and surface charge), and targeting ligand functionalization.
Abstract: Nanoparticle (NP) drug delivery systems (5−250 nm) have the potential to improve current disease therapies because of their ability to overcome multiple biological barriers and releasing a therapeutic load in the optimal dosage range. Rapid clearance of circulating nanoparticles during systemic delivery is a critical issue for these systems and has made it necessary to understand the factors affecting particle biodistribution and blood circulation half-life. In this review, we discuss the factors which can influence nanoparticle blood residence time and organ specific accumulation. These factors include interactions with biological barriers and tunable nanoparticle parameters, such as composition, size, core properties, surface modifications (pegylation and surface charge), and finally, targeting ligand functionalization. All these factors have been shown to substantially affect the biodistribution and blood circulation half-life of circulating nanoparticles by reducing the level of nonspecific uptake, de...
2,543 citations
TL;DR: The results indicate that the Bcl-2 family of proteins bind to the VDAC in order to regulate the mitochondrial membrane potential and the release of cytochrome c during apoptosis.
Abstract: During transduction of an apoptotic (death) signal into the cell, there is an alteration in the permeability of the membranes of the cell's mitochondria, which causes the translocation of the apoptogenic protein cytochrome c into the cytoplasm, which in turn activates death-driving proteolytic proteins known as caspases1,2 The Bcl-2 family of proteins, whose members may be anti-apoptotic or pro-apoptotic, regulates cell death by controlling this mitochondrial membrane permeability during apoptosis3,4,5, but how that is achieved is unclear Here we create liposomes that carry the mitochondrial porin channel (also called the voltage-dependent anion channel, or VDAC) to show that the recombinant pro-apoptotic proteins Bax and Bak accelerate the opening of VDAC, whereas the anti-apoptotic protein Bcl-xL closes VDAC by binding to it directly Bax and Bak allow cytochrome c to pass through VDAC out of liposomes, but passage is prevented by Bcl-xL In agreement with this, VDAC1-deficient mitochondria from a mutant yeast did not exhibit a Bax/Bak-induced loss in membrane potential and cytochrome c release, both of which were inhibited by Bcl-xL Our results indicate that the Bcl-2 family of proteins bind to the VDAC in order to regulate the mitochondrial membrane potential and the release of cytochrome c during apoptosis
2,222 citations
TL;DR: In cells undergoing apoptosis, an early, dramatic change occurs in the intracellular localization of Bax, and this redistribution of soluble Bax to organelle-bound GFP–Bax appears important for Bx to promote cell death.
Abstract: Bax, a member of the Bcl-2 protein family, accelerates apoptosis by an unknown mechanism. Bax has been recently reported to be an integral membrane protein associated with organelles or bound to organelles by Bcl-2 or a soluble protein found in the cytosol. To explore Bcl-2 family member localization in living cells, the green fluorescent protein (GFP) was fused to the NH2 termini of Bax, Bcl-2, and Bcl-XL. Confocal microscopy performed on living Cos-7 kidney epithelial cells and L929 fibroblasts revealed that GFP–Bcl-2 and GFP–Bcl-XL had a punctate distribution and colocalized with a mitochondrial marker, whereas GFP–Bax was found diffusely throughout the cytosol. Photobleaching analysis confirmed that GFP–Bax is a soluble protein, in contrast to organelle-bound GFP–Bcl-2. The diffuse localization of GFP–Bax did not change with coexpression of high levels of Bcl-2 or Bcl-XL. However, upon induction of apoptosis, GFP–Bax moved intracellularly to a punctate distribution that partially colocalized with mitochondria. Once initiated, this Bax movement was complete within 30 min, before cellular shrinkage or nuclear condensation. Removal of a COOH-terminal hydrophobic domain from GFP–Bax inhibited redistribution during apoptosis and inhibited the death-promoting activity of both Bax and GFP– Bax. These results demonstrate that in cells undergoing apoptosis, an early, dramatic change occurs in the intracellular localization of Bax, and this redistribution of soluble Bax to organelles appears important for Bax to promote cell death.
1,876 citations