Iron-Chelated Polydopamine Decorated Doxorubicin-Loaded Nanodevices for Reactive Oxygen Species Enhanced Cancer Combination Therapy

Li, Xu-Jing; Li, Wentong; Li, Zihaoran; Zhang, Liping; Gai, Chengcheng; Zhang, Weifen; Ding, Dejun

doi:10.3389/fphar.2019.00075

Cited by 16 publications

(8 citation statements)

References 40 publications

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“…Dried roots and rhizomes of Danshen have historically been used to treat cardiovascular and cerebrovascular diseases, and they are reported to have pharmacological activities 3 – 5 . Several Danshen products, including Fufang Danshen dripping pills, are used widely in clinical practice 6 , 7 . The bioactive ingredients in S. miltiorrhiza include water-soluble phenolic acids such as salvianolic acid A (Sal A), salvianolic acid B (Sal B), caffeic acid (CA), and rosmarinic acid (RA) 8 – 12 .…”

Section: Introductionmentioning

confidence: 99%

The methyl jasmonate-responsive transcription factor SmMYB1 promotes phenolic acid biosynthesis in Salvia miltiorrhiza

et al. 2021

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Water-soluble phenolic acids are major bioactive compounds in the medicinal plant species Salvia miltiorrhiza. Phenolic acid biosynthesis is induced by methyl jasmonate (MeJA) in this important Chinese herb. Here, we investigated the mechanism underlying this induction by analyzing a transcriptome library of S. miltiorrhiza in response to MeJA. Global transcriptome analysis identified the MeJA-responsive R2R3-MYB transcription factor-encoding gene SmMYB1. Overexpressing SmMYB1 significantly promoted phenolic acid accumulation and upregulated the expression of genes encoding key enzymes in the phenolic acid biosynthesis pathway, including cytochrome P450-dependent monooxygenase (CYP98A14). Dual-luciferase (dual-LUC) assays and/or an electrophoretic mobility shift assays (EMSAs) indicated that SmMYB1 activated the expression of CYP98A14, as well as the expression of genes encoding anthocyanin biosynthesis pathway enzymes, including chalcone isomerase (CHI) and anthocyanidin synthase (ANS). In addition, SmMYB1 was shown to interact with SmMYC2 to additively promote CYP98A14 expression compared to the action of SmMYB1 alone. Taken together, these results demonstrate that SmMYB1 is an activator that improves the accumulation of phenolic acids and anthocyanins in S. miltiorrhiza. These findings lay the foundation for in-depth studies of the molecular mechanism underlying MeJA-mediated phenolic acid biosynthesis and for the metabolic engineering of bioactive ingredients in S. miltiorrhiza.

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Section: Introductionmentioning

confidence: 99%

The methyl jasmonate-responsive transcription factor SmMYB1 promotes phenolic acid biosynthesis in Salvia miltiorrhiza

et al. 2021

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“…Furthermore, the intracellular ROS level was monitored using 2',7'-dichlorofluorescein diacetate as the fluorescence probe. 46 As shown in Figure 3C, a negligible fluorescence signal was observed when the cells were incubated with β-CDs/CeO 2 NPs compared with the control experiments. By contrast, high fluorescence signals were observed when the cells were incubated with H 2 O 2 .…”

Section: Sod-and Catalase-mimicking Activity Of β-Cds/ceo 2 Npsmentioning

confidence: 81%

“…The potential cytotoxicity of β-CDs/CeO 2 NPs was investigated in MTT assay as we reported earlier. 46 The HaCaT human keratinocyte cells line was selected to analyze cell viability in MTT assay (Sigma, MO, USA). HaCaT human keratinocyte cells were seeded into 96-well plates at a concentration of 1×10 4 cells/well and then incubated at 37°C and 5% CO 2 for 24 h to ensure proper stability and adherence.…”

Section: -(45-dimethylthiazolyl)-25-diphenyltetrazolium Bromide (Mmentioning

confidence: 99%

“…The role of nanocarriers in scavenging ROS was investigated using 2',7'-dichlorodihydrofluorescein diacetate. 46 The HaCaT human keratinocyte cells line was selected and seeded into 12-well plates at a concentration of 4×10 4 cells/well. Cells were incubated at 37°C and 5% CO 2 for 24 h to ensure proper stability and adherence, and then the culture medium was removed.…”

Section: Cellular Ros-scavenging Activitymentioning

confidence: 99%

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<p>Cyclodextrin-Modified CeO<sub>2</sub> Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis</p>

Wu¹,

Liu²,

Wang³

et al. 2020

IJN

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Reactive oxygen species (ROS)-induced oxidative stress plays a key role in the pathogenesis and progression of psoriasis by causing inflammation. Antioxidative strategies eradicating ROS may serve as effective and easy treatment options for psoriasis, while nanozymes with intrinsic antioxidant enzyme-like activity have not been explored for psoriasis treatment. The aim of this study is to fabricate β-cyclodextrins (β-CDs)-modified ceria nanoparticles (β-CDs/CeO 2 NPs) with drug-loaded and multimimic-enzyme activities for combinational psoriasis therapy. Methods: The β-CDs/CeO 2 NPs were synthesized by a hydrothermal method using unmodified β-CDs as a protecting agent. The structure, size and morphology were analyzed by dynamic light scattering, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy. Considering the superoxide dismutase (SOD)-and catalase-mimetic activities, the in vitro antioxidant activity of the β-CDs/CeO2 NPs was investigated. After dithranol (DIT) was loaded, the drug-loading capacity and release profile were determined by UV-visible light spectrophotometer and high-performance liquid chromatography. The anti-psoriatic efficacy was studied in the imiquimod (IMQ)-induced mouse model on the basis of morphological evaluation, psoriasis area and severity index calculation (PASI), and inflammatory cytokine expression. Results: The average particle size of the blank β-CDs/CeO 2 NPs was 60.89±0.32 nm with a polydispersity index (PDI) of 0.12, whereas that of the DIT-loaded NPs was 79.38±1.06 nm with a PDI of 0.27. TEM results showed the as-prepared NPs formed a uniform quasispherical shape with low polydispersity. XPS indicates synthesized NPs have a mixed Ce 3 + /Ce 4+ valence state. FTIR spectroscopy confirmed the presence of β-CDs and DIT in the NPs. Inhibition of superoxide anion rate by NPs could be reached to 79.4% in the presence of 200 µg/mL, and elimination of H 2 O 2 efficiency reached about 50% in the presence of 40 µg/ mL, demonstrating excellent superoxide dismutase-and catalase-mimicking activities, thereby providing remarkable cryoprotection against ROS-mediated damage. Furthermore, β-CDs on the surface endowed the NPs with drug-loading function via host-guest interactions. The entrapment efficiency and drug loading of DIT are 94.7% and 3.48%, respectively. The in vitro drug release curves revealed a suitable release capability of DIT@β-CDs/CeO 2 NPs under physiological conditions. In IMQ-induced psoriatic model, the DIT@β-CDs/CeO 2 NPs exhibited excellent therapeutic effect. Conclusion: This study may pave the way for the application of nanozyme β-CDs/CeO 2 NPs as a powerful tool for psoriasis therapy.

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“…Finally, Fe 3+ -burden PDA NPs (PDA NPs@Fe) were also charged with doxorubicin (DOX) to enhance their therapeutic activity. The capacity of this widely used drug to cause mitochondrial Fe accumulation and increase the production of reactive oxygen species (ROS) is well-known [ 20 , 21 ]. For this motive, it was chosen to produce a synergist effect with the chelated Fe 3+ and cause ROS overproduction [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Tailored-Made Polydopamine Nanoparticles to Induce Ferroptosis in Breast Cancer Cells in Combination with Chemotherapy

Nieto

Vega

Valle

2021

IJMS

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Ferroptosis is gaining followers as mechanism of selective killing cancer cells in a non-apoptotic manner, and novel nanosystems capable of inducing this iron-dependent death are being increasingly developed. Among them, polydopamine nanoparticles (PDA NPs) are arousing interest, since they have great capability of chelating iron. In this work, PDA NPs were loaded with Fe3+ at different pH values to assess the importance that the pH may have in determining their therapeutic activity and selectivity. In addition, doxorubicin was also loaded to the nanoparticles to achieve a synergist effect. The in vitro assays that were performed with the BT474 and HS5 cell lines showed that, when Fe3+ was adsorbed in PDA NPs at pH values close to which Fe(OH)3 begins to be formed, these nanoparticles had greater antitumor activity and selectivity despite having chelated a smaller amount of Fe3+. Otherwise, it was demonstrated that Fe3+ could be released in the late endo/lysosomes thanks to their acidic pH and their Ca2+ content, and that when Fe3+ was co-transported with doxorubicin, the therapeutic activity of PDA NPs was enhanced. Thus, reported PDA NPs loaded with both Fe3+ and doxorubicin may constitute a good approach to target breast tumors.

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Iron-Chelated Polydopamine Decorated Doxorubicin-Loaded Nanodevices for Reactive Oxygen Species Enhanced Cancer Combination Therapy

Cited by 16 publications

References 40 publications

The methyl jasmonate-responsive transcription factor SmMYB1 promotes phenolic acid biosynthesis in Salvia miltiorrhiza

The methyl jasmonate-responsive transcription factor SmMYB1 promotes phenolic acid biosynthesis in Salvia miltiorrhiza

<p>Cyclodextrin-Modified CeO<sub>2</sub> Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis</p>

Tailored-Made Polydopamine Nanoparticles to Induce Ferroptosis in Breast Cancer Cells in Combination with Chemotherapy

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