Rational design of ROS-responsive nanocarriers for targeted X-ray-induced photodynamic therapy and cascaded chemotherapy of intracranial glioblastoma

Zhang, Beibei; Xue, Rui; Sun, Chunyang

doi:10.1039/d2nr00436d

Cited by 18 publications

(14 citation statements)

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“…The polymeric prodrug PTP was synthesized, and its detailed synthesis is presented in Figure 1. First, the ROS-sensitive linker of TK was synthesized, and the 1 H NMR spectrum of TK was consistent with that reported in previous reports (Supplementary Figure S1) Xu et al, 2020;Zhang et al, 2022). Then, the ROSsensitive prodrug PTX-TK-COOH was obtained via a condensation reaction between PTX ( 1 H NMR result shown in Supplementary Figure S2) and TK, and the chemical framework of PTX-TK-COOH was clarified using the 1 H NMR result (Figure 2A) which revealed that the peak of the 2′-hydroxyl group of PTX at 3.6 ppm vanished and the signal of 2′-CH shifted from 4.7 to 5.9 ppm (Cao et al, 2018;Chang et al, 2020).…”

Section: Synthesis Of Tk Ptx-tk-cooh Mpeg-tk-ptx (Ptp)supporting

confidence: 79%

A co-delivery system based on chlorin e6-loaded ROS-sensitive polymeric prodrug with self-amplified drug release to enhance the efficacy of combination therapy for breast tumor cells

Wang

Yang

Qiu

et al. 2023

Front. Bioeng. Biotechnol.

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Background: Recently, various combination therapies for tumors have garnered popularity because of their synergistic effects in improving therapeutic efficacy and reducing side effects. However, incomplete intracellular drug release and a single method of combining drugs are inadequate to achieve the desired therapeutic effect.Methods: A reactive oxygen species (ROS)-sensitive co-delivery micelle (Ce6@PTP/DP). It was a photosensitizer and a ROS-sensitive paclitaxel (PTX) prodrug for synergistic chemo-photodynamic therapy. Micelles size and surface potential were measured. In vitro drug release, cytotoxicity and apoptosis were investigated.Results: Ce6@PTP/DP prodrug micelles exhibited good colloidal stability and biocompatibility, high PTX and Ce6 loading contents of 21.7% and 7.38%, respectively. Upon light irradiation, Ce6@PTP/DP micelles endocytosed by tumor cells can generate sufficient ROS, not only leading to photodynamic therapy and the inhibition of tumor cell proliferation, but also triggering locoregional PTX release by cleaving the thioketal (TK) bridged bond between PTX and methoxyl poly (ethylene glycol). Furthermore, compared with single drug-loaded micelles, the light-triggered Ce6@PTP/DP micelles exhibited self-amplified drug release and significantly greater inhibition of HeLa cell growth.Conclusion: The results support that PTX and Ce6 in Ce6@PTP/DP micelles exhibited synergistic effects on cell-growth inhibition. Thus, Ce6@PTP/DP micelles represent an alternative for realizing synergistic chemo-photodynamic therapy.

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Section: Synthesis Of Tk Ptx-tk-cooh Mpeg-tk-ptx (Ptp)supporting

confidence: 79%

A co-delivery system based on chlorin e6-loaded ROS-sensitive polymeric prodrug with self-amplified drug release to enhance the efficacy of combination therapy for breast tumor cells

Wang

Yang

Qiu

et al. 2023

Front. Bioeng. Biotechnol.

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Section: Resultsmentioning

confidence: 99%

“…Author: Please verify that the changes made to improve the English still retain your original meaning.As a kind of ionizing radiation, X-rays can not only directly damage cancer cells, but also decompose and ionize water molecules, inducing the production of reactive oxygen species (ROS). 18 It is reported that GO may increase intracellular ROS in various ways. 19 The surface and edge of GO are rich in oxygen-containing functional groups, such as First, NPC cells C666-1 and HK-1 were given control group and experimental group without GO or with GO, and then irradiated.…”

Section: Go Enhanced the Cell Apoptosis By Reducing Bcl-2 And Raising...mentioning

confidence: 99%

Radiosensitization of Nasopharyngeal Carcinoma by Graphene Oxide Nanosheets to Reduce Bcl-2 Level

Zhou

et al. 2023

Langmuir

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There are many treatments for nasopharyngeal carcinoma (NPC), but none of them are very effective. Radiotherapy is used extensively in NPC treatment, but radioresistance is a major problem. Graphene oxide (GO) has been previously studied in cancer treatment, and this study is aimed to explore its role in radiosensitization of NPC. Therefore, graphene oxide nanosheets were prepared, and the relationship between GO and radioresistance was explored. The GO nanosheets were synthesized by a modified Hummers' method. The morphologies of the GO nanosheets were characterized by field-emission environmental scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The morphological changes and radiosensitivity of C666-1 and HK-1 cells with or without the GO nanosheets were observed by an inverted fluorescence microscopy and laser scanning confocal microscopy (LSCM). Colony formation assay and Western Blot were applied for analysis of NPC radiosensitivity. The assynthesized GO nanosheets have lateral dimensions (sizes ∼1 μm) and exhibit a thin wrinkled two-dimensional lamellar structure with slight folds and crimped edges (thickness values ∼1 nm). C666-1 cells with the GO was significantly changed the morphology of cells postirradiation. The full field of view visualized by a microscope showed the shadow of dead cells or cell debris. The synthesized graphene oxide nanosheets inhibited cell proliferation, promoted cell apoptosis, and inhibited the expression of Bcl-2 in C666-1 and HK-1 cells but increased the level of Bax. The GO nanosheets could affect the cell apoptosis and reduce the pro-survival protein Bcl-2 related to the intrinsic mitochondrial pathway. The GO nanosheets could enhance radiosensitivity, which might be a radioactive material in NPC cells.

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“…299–306 Sun's team designed a multifunctional nanocarrier, T-TKNPVP, consisting of angiopep-2 (Ang) modified Ang-PEG-DSPE and TK-bridged PEG-TK-PTX conjugated compounds, as shown in Fig. 25(b, d and e). 307 Active targeting of X-PDT and cascade ROS-enhanced chemotherapy were achieved using this nanosystem. Precise chemotherapy is achieved by Ang-assisted translocation across the blood–brain barrier (BBB) to target glioblastoma (GBM) cells and by transcranial X-rays stimulation to generate cytotoxic ROS for the destruction of thione (TK) to promote the release and action of paclitaxel (PTX).…”

Section: Current Medical Applicationsmentioning

confidence: 99%

Catalytic nanotechnology of X-ray photodynamics for cancer treatments

Zhang

Guo

et al. 2023

Biomater. Sci.

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Rational design of ROS-responsive nanocarriers for targeted X-ray-induced photodynamic therapy and cascaded chemotherapy of intracranial glioblastoma

Abstract: Glioblastoma (GBM) is the most lethal primary intracranial tumor because of its high invasiveness and recurrence. Specifically, nanocarriers with blood–brain barrier (BBB) penetration and transcranial-controlled drug release and activation are...

Cited by 18 publications

References 50 publications

A co-delivery system based on chlorin e6-loaded ROS-sensitive polymeric prodrug with self-amplified drug release to enhance the efficacy of combination therapy for breast tumor cells

A co-delivery system based on chlorin e6-loaded ROS-sensitive polymeric prodrug with self-amplified drug release to enhance the efficacy of combination therapy for breast tumor cells

Radiosensitization of Nasopharyngeal Carcinoma by Graphene Oxide Nanosheets to Reduce Bcl-2 Level

Catalytic nanotechnology of X-ray photodynamics for cancer treatments

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