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Glutathione (GSH) is a crucial factor in limiting the effects of chemodynamic therapy (CDT) and ferroptosis, an iron-based cell death pathway. Based on this, we constructed iron-rich mesoporous dopamine (MPDA@Fe) nanovehicles with a dual-GSH depletion function by combining MPDA and Fe. Poly (ethylene glycol) (PEG) was further modified to provide desirable stability (PM@Fe) and glucose oxidase (GOx) was grafted onto PM@Fe (GPM@Fe) to address the limitation of hydrogen peroxide (H 2 O 2 ). After the nanoparticles reached the tumor site, the weakly acidic microenvironment promoted the release of Fe. Then Fe II reacted with H 2 O 2 to generate hydroxyl radical (OH) and Fe III . The generated Fe III was reduced to Fe II by GSH, which circularly participated in the Fenton reaction and continuously produced tumor inhibitory free radicals. Meanwhile, GOx consumed glucose to provide H 2 O 2 for the reaction. MPDA had also been reported to deplete GSH. Therefore, dual consumption of GSH led to the destruction of intracellular redox balance and inhibition of glutathione-dependent peroxidase 4 (GPX4) expression, resulting in an increase in lipid peroxides (LPO) and further induction of ferroptosis. Additionally, MPDA-mediated photothermal therapy (PTT) raised the temperature of tumor area and produced photothermal-enhanced cascade effects. Hence, the synergistic strategy that combined dual-GSH depletion-induced ferroptosis, enhanced CDT and photothermal cascade enhancement based on MPDA@Fe could provide more directions for designing nanomedicines for cancer treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this paper, a redox-triggered drug delivery system of DOX/MSN-Au was prepared for chemo-photothermal synergistic therapy. The ultra-small gold nanoparticles (NPs) were appended to the openings of mesoporous silica nanoparticles (MSN) by Au-S bonds as the gatekeepers. Meanwhile, the gold NPs could be heated to high temperature by the near infrared (NIR) light irradiation, which is conducive to photothermal therapy. X-ray photoelectron spectroscopy (XPS) and Fourier Transform Infrared Spectrometer (FT-IR) spectra confirmed the formation of MSN-SH and MSN-Au. An in vitro NIR-induced photothermal study indicated that MSN-Au possessed concentration-dependent and power-dependent photothermal conversion capacity. Doxorubicin (DOX) was selected as the model drug loaded in the MSN. In vitro drug release showed that DOX released faster in the presence of glutathione (GSH) or NIR laser irradiation than without GSH or NIR irradiation, which suggested that the system had potentials for redox-responsive and NIR-triggered drug release. Confocal Laser Scanning Microscope (CLSM) was performed to evaluate the cellular uptake performance of DOX/MSN-Au. The cytotoxicity assay indicated that DOX/MSN-Au had a synergistic therapeutic effect by the combination of chemotherapy and photothermal therapy. This work suggested that MSN-Au could be explored as a redox-triggered drug delivery system for the chemo-photothermal synergistic therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

An efficient and intelligent nano-carrier that combines cell imaging with near infrared (NIR) light and redox dual-responsive drug delivery was successfully prepared. The hollow mesoporous carbon (HMC) nanoparticles with high photothermal conversion ability were developed to increase the drug loading efficiency and realize chemotherapy and photothermal synergetic therapy. The photo-stable and luminescent carbon dots (CDs) were prepared from branched polyethyleneimine (PEI) by hydrothermal reaction. The PEI CDs (CD PEI ) were grafted on the openings of HMC as the "gatekeepers" via disulfide units (HMC-SS-CD PEI ) to prevent the premature release of doxorubicin (DOX). In the presence of GSH, the CD PEI separated from HMC due to the breakage of disulfide bonds, thus triggering the rapid release of the encapsulated drug. In addition, the release rate of DOX could be further accelerated by NIR light irradiation due to the increased temperature which would decrease the interaction between HMC and DOX. The fluorescence of the CD PEI is quenched when being attached to the HMC, while it is recovered when the CD PEI breaking away from HMC. Hence, the fluorescent CD PEI not only act as a gatekeeper to control drug release but also play a vital role in monitoring the process of the drug delivery. The developed HMC-SS-CD PEI showed dual-responsive drug release property and could be used as visible nano-platforms for chemo-photothermal synergistic therapy., (Copyright © 2017. Published by Elsevier Inc.)

In this study, hollow mesoporous carbon nanoparticles (HMCN) and mesoporous carbon nanoparticles (MCN) were used as near-infrared region (NIR) nanomaterials and drug nanocarriers were prepared using different methods. A comparison between HMCN and MCN was performed with regard to the NIR-induced photothermal effect and drug loading efficiency. The results of NIR-induced photothermal effect test demonstrated that HMCN-COOH had a better photothermal conversion efficacy than MCN-COOH. Given the prominent photothermal effect of HMCN-COOH in vitro, the chemotherapeutic drug DOX was chosen as a model drug to further evaluate the drug loading efficiencies and NIR-triggered drug release behaviors of the nanocarriers. The drug loading efficiency of DOX/HMCN-COOH was found to be up to 76.9%, which was higher than that of DOX/MCN-COOH. In addition, the use of an 808nm NIR laser markedly increased the release of DOX from both carbon carriers in pH 5.0 PBS and pH 7.4 PBS. Cellular photothermal tests involving A549 cells demonstrated that HMCN-COOH had a much higher photothermal efficacy than MCN-COOH. Cell viability experiments and flow cytometry were performed to evaluate the therapeutic effect of DOX/HMCN-COOH and the results obtained demonstrated that DOX/HMCN-COOH had a synergistic therapeutic effect in cancer treatment involving a combination of chemotherapy and photothermal therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In this paper, a smart nanocarrier (MSNs-SS-CDPAA) is developed for redox-responsive controlled drug delivery and in vivo bioimaging by grafting fluorescent carbon dots to the surface of mesoporous silica nanoparticles (MSNs) via disulfide bonds. The polyanion polymer poly(acrylic acid) (PAA) was used to prepare the carboxyl-abundant carbon dots (CDPAA) by hydrothermal polymerization. The negatively charged CDPAA were anchored to the openings of MSNs containing the disulfide bonds through amidation and were used as gatekeepers for trapping the drugs within the pores. The in vitro release results indicated that the prepared MSNs-SS-CDPAA/DOX showed highly redox-responsive drug release in pH 7.4 and pH 5.0 PBS. In addition, the redox-responsive release mechanism was studied by measurement of the Zeta potential and fluorescence spectrophotometry. The prepared MSNs-SS-CDPAA exhibited excellent biocompatibility and fluorescence properties. Confocal laser scanning microscopy (CLSM) showed that MSNs-SS-CDPAA could emit blue, green and red fluorescence at an excitation wavelength of 408, 488 and 561nm, respectively. In addition, MSNs-SS-CDPAA/DOX exhibited a high cellular uptake as shown by CDPAA imaging and a therapeutic effect on cancer cells by MTT assay. This study describes a novel strategy for simultaneously controlled drug delivery and real-time imaging to track the behavior of nanoparticles during tumor therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)