scholarly journals MOF-Based Nanoagent Enables NIR-Triggered Dual Damage to Mitochondria via Synergistically Reinforced Oxidative Stress and Calcium Overload

2021 ◽  
Author(s):  
Zhiyuan Tian ◽  
Weier Bao ◽  
Ming Liu ◽  
Jiaqi Meng ◽  
Siyuan Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Near Infrared ◽  
Calcium Influx ◽  
Uv Light ◽  
Calcium Overload ◽  
Tumor Xenograft ◽  
Nir Light ◽  
Xenograft Models ◽  
Photoacid Generator

Abstract We herein developed a core-shell type antitumor nanoagent based on the synergistically reinforced oxidative stress and calcium overload to mitochondria, both of which were triggered by near-infrared (NIR) light. The folic acid (FA) moiety decorated on MOF shells enabled efficient cellular uptake of nanoagents. The upconversion nanoparticle (UCNP) core converted NIR light to ultraviolet (UV) light with the latter catalyzed Fe3+-to-Fe2+ reduction and simultaneously activated the photoacid generator encapsulated in the cavities of MOFs, which enabled the release of free Fe2+ and photoacidification of intracellular microenvironment, respectively. The overexpressed H2O2 in the mitochondria, highly reactive Fe2+ and acidic milieu synergistically reinforced Fenton reactions for producing lethal hydroxyl radicals in mitochondria. Moreover, the photoacidification of plasma induced calcium influx, leading to calcium overload in the mitochondria. The therapeutic potency of the nanoagent based on the dual mitochondrial damage has been unequivocally confirmed in cell- and patient-derived tumor xenograft models in vivo.

scholarly journals MOFs-based nanoagent enables dual mitochondrial damage in synergistic antitumor therapy via oxidative stress and calcium overload

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Weier Bao ◽  
Ming Liu ◽  
Jiaqi Meng ◽  
Siyuan Liu ◽  
Shuang Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Near Infrared ◽  
Calcium Influx ◽  
Calcium Overload ◽  
Tumor Xenograft ◽  
Great Promise ◽  
Antitumor Therapy ◽  
Nir Light ◽  
Metal Organic

AbstractTargeting subcellular organelle with multilevel damage has shown great promise for antitumor therapy. Here, we report a core-shell type of nanoagent with iron (III) carboxylate metal-organic frameworks (MOFs) as shell while upconversion nanoparticles (UCNPs) as core, which enables near-infrared (NIR) light-triggered synergistically reinforced oxidative stress and calcium overload to mitochondria. The folate decoration on MOFs shells enables efficient cellular uptake of nanoagents. Based on the upconversion ability of UCNPs, NIR light mediates Fe3+-to-Fe2+ reduction and simultaneously activates the photoacid generator (pHP) encapsulated in MOFs cavities, which enables release of free Fe2+ and acidification of intracellular microenvironment, respectively. The overexpressed H2O2 in mitochondria, highly reactive Fe2+ and acidic milieu synergistically reinforce Fenton reactions for producing lethal hydroxyl radicals (•OH) while plasma photoacidification inducing calcium influx, leading to mitochondria calcium overload. The dual-mitochondria-damage-based therapeutic potency of the nanoagent has been unequivocally confirmed in cell- and patient-derived tumor xenograft models in vivo.

scholarly journals Novel concept of the smart NIR-light–controlled drug release of black phosphorus nanostructure for cancer therapy

2018 ◽  
Vol 115 (3) ◽  
pp. 501-506 ◽  
Author(s):  
Meng Qiu ◽  
Dou Wang ◽  
Weiyuan Liang ◽  
Liping Liu ◽  
Yin Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Drug Release ◽  
Drug Delivery System ◽  
Delivery System ◽  
Near Infrared ◽  
Black Phosphorus ◽  
Deep Penetration ◽  
Nir Light

A biodegradable drug delivery system (DDS) is one the most promising therapeutic strategies for cancer therapy. Here, we propose a unique concept of light activation of black phosphorus (BP) at hydrogel nanostructures for cancer therapy. A photosensitizer converts light into heat that softens and melts drug-loaded hydrogel-based nanostructures. Drug release rates can be accurately controlled by light intensity, exposure duration, BP concentration, and hydrogel composition. Owing to sufficiently deep penetration of near-infrared (NIR) light through tissues, our BP-based system shows high therapeutic efficacy for treatment of s.c. cancers. Importantly, our drug delivery system is completely harmless and degradable in vivo. Together, our work proposes a unique concept for precision cancer therapy by external light excitation to release cancer drugs. If these findings are successfully translated into the clinic, millions of patients with cancer will benefit from our work.

scholarly journals PGRMC1-dependent lipophagy promotes ferroptosis in paclitaxel-tolerant persister cancer cells

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Ji Hyeon You ◽  
Jaewang Lee ◽  
Jong-Lyel Roh
Keyword(s):  
Cancer Cells ◽  
Lipid Droplets ◽  
Tumor Xenograft ◽  
Acid Oxidation ◽  
Mouse Tumor ◽  
Autophagy Induction ◽  
Highly Sensitive ◽  
Xenograft Models

Abstract Background Progesterone receptor membrane component 1 (PGRMC1) is a heme-binding protein inducing dimerization with cytochrome P450, which mediates chemoresistance. Increased PGRMC1 expression is found in multiple types of resistant cancers, but the role of PGRMC1 in the ferroptosis of cancer cells remains unrevealed. Therefore, we examined the role of PGRMC1 in promoting ferroptosis in paclitaxel-tolerant persister cancer cells (PCC). Methods The effects of ferroptosis inducers and PGRMC1 gene silencing/overexpression were tested on head and neck cancer (HNC) cell lines and mouse tumor xenograft models. The results were analyzed about cell viability, death, lipid ROS and iron production, mRNA/protein expression and interaction, and lipid assays. Results PCC had more free fatty acids, lipid droplets, and fatty acid oxidation (FAO) than their parental cells. PCC was highly sensitive to inhibitors of system xc− cystine/glutamate antiporter (xCT), such as erastin, sulfasalazine, and cyst(e)ine deprivation, but less sensitive to (1S,3R)-RSL3. PGRMC1 silencing in PCC reduced ferroptosis sensitivity by xCT inhibitors, and PGRMC1 overexpression in parental cells increased ferroptosis by xCT inhibitors. Lipid droplets were degraded along with autophagy induction and autophagosome formation by erastin treatment in PCC. Lipophagy was accompanied by increased tubulin detyrosination, which was increased by SIRT1 activation but decreased by SIRT1 inhibition. FAO and lipophagy were also promoted by the interaction between lipid droplets and mitochondria. Conclusion PGRMC1 expression increased FAO and ferroptosis sensitivity from in vivo mice experiments. Our data suggest that PGRMC1 promotes ferroptosis by xCT inhibition in PCC.

scholarly journals Self-Assembled Monolayers of Copper Sulfide Nanoparticles on Glass as Antibacterial Coatings

Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 352 ◽  
Author(s):  
Chiara Gargioni ◽  
Mykola Borzenkov ◽  
Laura D’Alfonso ◽  
Paola Sperandeo ◽  
Alessandra Polissi ◽  
...  
Keyword(s):  
Thermal Effect ◽  
Bacterial Adhesion ◽  
Copper Sulfide ◽  
Near Infrared ◽  
Thermal Action ◽  
Self Assembled Monolayers ◽  
Nir Light ◽  
Copper Release ◽  
Assembled Monolayers

We developed an easy and reproducible synthetic method to graft a monolayer of copper sulfide nanoparticles (CuS NP) on glass and exploited their particular antibacterial features. Samples were fully characterized showing a good stability, a neat photo-thermal effect when irradiated in the Near InfraRed (NIR) region (in the so called “biological window”), and the ability to release controlled quantities of copper in water. The desired antibacterial activity is thus based on two different mechanisms: (i) slow and sustained copper release from CuS NP-glass samples, (ii) local temperature increase caused by a photo-thermal effect under NIR laser irradiation of CuS NP–glass samples. This behavior allows promising in vivo applications to be foreseen, ensuring a “static” antibacterial protection tailored to fight bacterial adhesion in the critical timescale of possible infection and biofilm formation. This can be reinforced, when needed, by a photo-thermal action switchable on demand by an NIR light.

H2O2/near-infrared light-responsive nanotheronostics for MRI-guided synergistic chemo/photothermal cancer therapy

Nanomedicine ◽  
2019 ◽  
Vol 14 (16) ◽  
pp. 2189-2207
Author(s):  
Yiming Yu ◽  
Li Zhang ◽  
Miao Wang ◽  
Zhe Yang ◽  
Leping Lin ◽  
...  
Keyword(s):  
Near Infrared ◽  
Tumor Model ◽  
Mri Contrast Agent ◽  
Infrared Light ◽  
Antitumor Effects ◽  
Mri Contrast ◽  
Nir Light ◽  
Nir Laser

Aim: To develop a H2O2/near-infrared (NIR) laser light-responsive nanoplatform (manganese-doped Prussian blue@polypyrrole [MnPB@PPy]) for synergistic chemo/photothermal cancer theranostics. Materials & methods: Doxorubicin (DOX) was loaded onto the surface of polypyrrole shells. The in vitro and in vivo MRI performance and anticancer effects of these nanoparticles (NPs) were evaluated. Results: The MnPB@PPy NPs could not only generate heat under NIR laser irradiation for cancer photothermal therapy but also act as an excellent MRI contrast agent. The loaded DOX could be triggered to release by both NIR light and H2O2 to enhance synergistic therapeutic efficacy. The antitumor effects were confirmed by in vitro cellular cytotoxicity assays and in vivo treatment in a xenograft tumor model. Conclusion: The designed H2O2/NIR light-responsive MnPB@PPy-DOX NPs hold great potential for future biomedical applications.

scholarly journals Testing of resveratrol microemulsion photostability and protective effect against UV induced oxidative stress

2017 ◽  
Vol 67 (2) ◽  
pp. 247-256 ◽  
Author(s):  
Vaida Juškaitė ◽  
Kristina Ramanauskienė ◽  
Vitalis Briedis
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Ultraviolet Radiation ◽  
Uv Light ◽  
Biological Testing ◽  
Human Keratinocyte ◽  
Improved Stability ◽  
Rate Profile

Abstract Resveratrol is well known for its antioxidant activity and susceptibility to ultraviolet radiation. Development of formulations providing improved stability and relevant drug delivery of resveratrol is still a challenging task. The aim of this study was to determine protective characteristics of formulated microemulsions by evaluating photoisomerization of resveratrol and to investigate the effects of resveratrol on human keratinocyte cells under oxidative stress caused by ultraviolet radiation. Incorporation of resveratrol into microemulsions resulted in increased photostability of active compounds and the results demonstrated that photodegradation of resveratrol was significantly delayed. Results of biopharmaceutical evaluation in vitro demonstrated that up to 60 % of resveratrol was released from microemulsions within 6 hours under a constant release rate profile. In vivo biological testing confirmed the ability of resveratrol to protect cells from oxidative stress and to increase cell viability. It was concluded that microemulsions might be considered in the development of UV light sensitive compounds.

scholarly journals Biocompatible near-infrared quantum dots delivered to the skin by microneedle patches record vaccination

2019 ◽  
Vol 11 (523) ◽  
pp. eaay7162 ◽  
Author(s):  
Kevin J. McHugh ◽  
Lihong Jing ◽  
Sean Y. Severt ◽  
Mache Cruz ◽  
Morteza Sarmadi ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Human Skin ◽  
Data Storage ◽  
Near Infrared ◽  
Learning Algorithm ◽  
Ex Vivo ◽  
Neutralizing Antibody ◽  
Nir Light ◽  
Antibody Titers

Accurate medical recordkeeping is a major challenge in many low-resource settings where well-maintained centralized databases do not exist, contributing to 1.5 million vaccine-preventable deaths annually. Here, we present an approach to encode medical history on a patient using the spatial distribution of biocompatible, near-infrared quantum dots (NIR QDs) in the dermis. QDs are invisible to the naked eye yet detectable when exposed to NIR light. QDs with a copper indium selenide core and aluminum-doped zinc sulfide shell were tuned to emit in the NIR spectrum by controlling stoichiometry and shelling time. The formulation showing the greatest resistance to photobleaching after simulated sunlight exposure (5-year equivalence) through pigmented human skin was encapsulated in microparticles for use in vivo. In parallel, microneedle geometry was optimized in silico and validated ex vivo using porcine and synthetic human skin. QD-containing microparticles were then embedded in dissolvable microneedles and administered to rats with or without a vaccine. Longitudinal in vivo imaging using a smartphone adapted to detect NIR light demonstrated that microneedle-delivered QD patterns remained bright and could be accurately identified using a machine learning algorithm 9 months after application. In addition, codelivery with inactivated poliovirus vaccine produced neutralizing antibody titers above the threshold considered protective. These findings suggest that intradermal QDs can be used to reliably encode information and can be delivered with a vaccine, which may be particularly valuable in the developing world and open up new avenues for decentralized data storage and biosensing.

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