A pH-Activatable nanoparticle for dual-stage precisely mitochondria-targeted photodynamic anticancer therapy

Qi, Ting; Chen, Binlong; Wang, Zenghui; Du, Hongchuan; Liu, Dechun; Yin, Qingqing; Liu, Bangyuan; Zhang, Qiang; Wang, Yiguang

doi:10.1016/j.biomaterials.2019.05.030

Cited by 84 publications

(62 citation statements)

References 42 publications

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“…A more recent report suggested that mitochondrial targeting PDT could inhibit mitochondrial respiration, leading to a change in intramitochondrial oxygen levels, and further enhancing the PDT effect under hypoxic conditions Ref [28]. In addition, the overproduction of ROS in mitochondria during the PDT process causes the depolarization of the mitochondria membrane, resulting in the release of proapoptotic proteins, particularly cytochrome c, from the inner mitochondrial membrane to the cytosol, further activating apoptosis cell death [25,29,30]. These findings imply the importance of mitochondrial targeting in PDT applications.…”

Section: Figurementioning

confidence: 99%

“…The tumor accumulation of this system is achieved by the enhanced permeability and retention (EPR) effect, followed by endocytosis. During the acidification of the endosome environment, the polymeric NPs rapidly dissociate, leading to the release of the TPPa, which could then effectively escape from the endosome and accumulate in the mitochondria [29]. A mitochondrially selective PS, namely IR-Pyr, has been used to form micellar aggregates through electrostatic interactions with negatively charged hyaluronic acid (HA) molecules to produce dual-targeting ability towards a tumor and its mitochondrial compartment.…”

Section: Mitochondrial Targeted Ps In Drug Delivery Systemmentioning

confidence: 99%

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Therapeutic Strategies for Regulating Mitochondrial Oxidative Stress

et al. 2020

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There have been many reports on the relationship between mitochondrial oxidative stress and various types of diseases. This review covers mitochondrial targeting photodynamic therapy and photothermal therapy as a therapeutic strategy for inducing mitochondrial oxidative stress. We also discuss other mitochondrial targeting phototherapeutic methods. In addition, we discuss anti-oxidant therapy by a mitochondrial drug delivery system (DDS) as a therapeutic strategy for suppressing oxidative stress. We also describe cell therapy for reducing oxidative stress in mitochondria. Finally, we discuss the possibilities and problems associated with clinical applications of mitochondrial DDS to regulate mitochondrial oxidative stress.Biomolecules 2020, 10, 83 2 of 23 Parkinson's and Alzheimer's diseases, by the direct neutralization of ROS and by suppressing inflammation [5,6]. Furthermore, CoQ 10 , a potent ubiquinone antioxidant, has been reported to show significant protective effects on mitochondria of the pancreatic beta cells during the oxidative stress induced by the chronic use of tacrolimus [7]. Due to the highly hydrophobic characteristics and the fact that most of the antioxidant molecules accumulate in a nonspecific manner, a high dose is needed to obtain the desired effects. Thus, the selective delivery of this compound would be expected to further strengthen its effectivity.In the context of cancer therapy, mitochondrial ROS were found to play an important role as a signaling molecule in controlling cell proliferation by virtue of its ability to regulate the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway [8]. Moreover, antioxidant activity, such as GSH and thioredoxin, was also reported to be essential for the initiation of and the progression of cancer. Inhibition of the antioxidant activity resulted in a significant reduction in tumor progression and metastasis [9][10][11]. These findings suggest that cancer cells are maintained under conditions of ROS stress and that antioxidant supplementation may be irrelevant for cancer therapy [12][13][14]. However, ROS interact with several major biologically active molecules such as proteins, lipids, and nucleic acids, leading to irreversible oxidative damage and the further induction of lethal effects for the cells. Therefore, promoting ROS production could be a promising strategy for treating tumors. There are numerous methods that can be employed to promote ROS levels in cancers, i.e., depleting or inhibiting antioxidant activity [15,16] and inhibiting the mitochondrial respiratory system [17], and producing an excessive amount of ROS through photochemical reactions. The latter effort shows a high selectivity for tumor cells, making it more encouraging in contrast to other efforts.This review focuses on therapeutic strategies for regulating mitochondrial oxidative stress. The main theme includes therapeutic strategies designed to induce oxidative stress and suppress mitochondrial oxidative stress (Figure 1). As ...

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Section: Figurementioning

confidence: 99%

Section: Mitochondrial Targeted Ps In Drug Delivery Systemmentioning

confidence: 99%

Therapeutic Strategies for Regulating Mitochondrial Oxidative Stress

et al. 2020

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“…This type of micellar nanoparticles exhibited fast and ultrasensitive response to changes over the entire physiological arrange of pH, depending on the types of tertiary amine substituents. In addition to functioning as ultra-pH-sensitive fluorescent nanoprobes, these nanoparticles can be used for developing pH-activatable nanotherapies and nanovaccines [ 209 , 210 ].…”

Section: Materials and Delivery Vehicles Responsive To Inflammatory Smentioning

confidence: 99%

Bioresponsive drug delivery systems for the treatment of inflammatory diseases

Ding

et al. 2020

Journal of Controlled Release

106

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Inflammation is intimately related to the pathogenesis of numerous acute and chronic diseases like cardiovascular disease, inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative diseases. Therefore anti-inflammatory therapy is a very promising strategy for the prevention and treatment of these inflammatory diseases. To overcome the shortcomings of existing anti-inflammatory agents and their traditional formulations, such as nonspecific tissue distribution and uncontrolled drug release, bioresponsive drug delivery systems have received much attention in recent years. In this review, we first provide a brief introduction of the pathogenesis of inflammation, with an emphasis on representative inflammatory cells and mediators in inflammatory microenvironments that serve as pathological fundamentals for rational design of bioresponsive carriers. Then we discuss different materials and delivery systems responsive to inflammation-associated biochemical signals, such as pH, reactive oxygen species, and specific enzymes. Also, applications of various bioresponsive drug delivery systems in the treatment of typical acute and chronic inflammatory diseases are described. Finally, crucial challenges in the future development and clinical translation of bioresponsive anti-inflammatory drug delivery systems are highlighted.

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“…The pH-responsive TPNBS could augment theranostic efficacy by providing prolonged blood circulation with reduced systemic toxicity, effective tumor accumulation, improved tissue penetration, tumor oxygenation, and tumoral pH-sensitive imaging signal and therapeutic efficacy enhancement. Qi et al (2019) reported a pH-responsive simultaneous activation of FI and PDT. Fluorescent dye (Cy7.5), labeled as a pH-responsive copolymer, poly(ethylene glycol)-b-poly(2-(isopropylamino) ethyl methacrylate) (mPEG-b-PDPA-Cy7.5) micelles were encapsulated with a mitochondriatargeted photosensitizer, triphenylphosphonium-conjugated pyropheophorbide-a (TPPa).…”

Section: Ph-responsive Tpnbs In Pdtmentioning

confidence: 99%

Recent Developments in Pathological pH-Responsive Polymeric Nanobiosensors for Cancer Theranostics

Kumar

Park

2020

Front. Bioeng. Biotechnol.

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Polymeric nanobiosensors (PNBS) that respond to tumor-related factors, including pH, have shown great potential for disease detection owing to their selectivity and sensitivity. PNBS can be converted into theranostic polymeric nanobiosensors (TPNBS) by incorporating therapeutic cargo, thereby enabling concomitant diagnoses and therapy of targeted diseases. The polymeric compartments in TPNBS play a significant role in the development and therapeutic efficacy of nanobiosensors. Polymers enhance the stability, biocompatibility, and selective or effective accumulation of nanobiosensors at desired pathological sites. The intrinsic pH sensitivity of either the polymers in TPNBS or the TPNBS themselves provides integrated potentialities such as cogent accumulation of TPNBS at the tumor, augmented tumor penetration, cellular uptake, and theranostic activation, including enhanced bioimaging signals and controlled release of therapeutics. In this review, we summarize recent developments in the design, preparation, and characterization of pH-responsive TPNBS and their ability to behave as efficient in vivo nanotheranostic agents in acidic cancer environments.

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A pH-Activatable nanoparticle for dual-stage precisely mitochondria-targeted photodynamic anticancer therapy

Cited by 84 publications

References 42 publications

Therapeutic Strategies for Regulating Mitochondrial Oxidative Stress

Therapeutic Strategies for Regulating Mitochondrial Oxidative Stress

Bioresponsive drug delivery systems for the treatment of inflammatory diseases

Recent Developments in Pathological pH-Responsive Polymeric Nanobiosensors for Cancer Theranostics

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