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      Magnetically guided theranostics: montmorillonite-based iron/platinum nanoparticles for enhancing in situ MRI contrast and hepatocellular carcinoma treatment

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          Abstract

          In Asia, including Taiwan, malignant tumors such as Hepatocellular carcinoma (HCC) one of the liver cancer is the most diagnosed subtype. Magnetic resonance imaging (MRI) has been a typical diagnostic method for accurately diagnosing HCC. When it is difficult to demonstrate non-enhanced MRI of tumors, radiologists can use contrast agents (such as Gd 3+, Fe 3O 4, or FePt) for T1-weighted and T2-weighted imaging remain in the liver for a long time to facilitate diagnosis via MRI. However, it is sometimes difficult for T2-weighted imaging to detect small tumor lesions because the liver tissue may absorb iron ions. This makes early cancer detection a challenging goal. This challenge has prompted current research to create novel nanocomposites for enhancing the noise-to-signal ratio of MRI. To develop a method that can more efficiently diagnose and simultaneously treat HCC during MRI examination, we designed a functionalized montmorillonite (MMT) material with a porous structure to benefit related drugs, such as mitoxantrone (MIT) delivery or as a carrier for the FePt nanoparticles (FePt NPs) to introduce cancer therapy. Multifunctional FePt@MMT can simultaneously visualize HCC by enhancing MRI signals, treating various diseases, and being used as an inducer of magnetic fluid hyperthermia (MFH). After loading the drug MIT, FePt@MMT-MIT provides both MFH treatment and chemotherapy in one nanosystem. These results ultimately prove that functionalized FePt@MMT-MIT could be integrated as a versatile drugs delivery system by combining with MRI, chemotheraeutic drugs, and magnetic guide targeting.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12951-021-01052-7.

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          Prolyl-4-hydroxylase α subunit 2 promotes breast cancer progression and metastasis by regulating collagen deposition

          Background Increased collagen deposition provides physical and biochemical signals to support tumor growth and invasion during breast cancer development. Therefore, inhibition of collagen synthesis and deposition has been considered a strategy to suppress breast cancer progression. Collagen prolyl-4-hydroxylase α subunit 2 (P4HA2), an enzyme hydroxylating proline residues in -X-Pro-Gly- sequences, is a potential therapeutic target for the disorders associated with increased collagen deposition. However, expression and function of P4HA2 in breast cancer progression are not well investigated. Methods Gene co-expression analysis was performed in the published microarray datasets to identify potential regulators of collagen I, III, and IV in human breast cancer tissue. Expression of P4HA2 was silenced by shRNAs, and its activity was inhibited by 1, 4-DPCA, a prolyl-4-hydroxylase inhibitor. Three-dimensional culture assay was used to analyze roles of P4HA2 in regulating malignant phenotypes of breast cancer cells. Reduced deposition of collagen I and IV was detected by Western blotting and immunofluorescence. Control and P4HA2-silenced breast cancer cells were injected into fat pad and tail vein of SCID mice to examine effect of P4HA2 on tumor growth and lung metastasis. Results Using gene co-expression analysis, we showed that P4HA2 was associated with expression of Col1A1, Col3A1, and Col4A1 during breast cancer development and progression. P4HA2 mRNA levels were significantly upregulated in breast cancer compared to normal mammary tissue. Increased mRNA levels of P4HA2 correlated with poor clinical outcome in breast cancer patients, which is independent of estrogen receptor status. Silencing P4HA2 expression or treatment with the P4HA inhibitor significantly inhibited cell proliferation and suppressed aggressive phenotypes of breast cancer cells in 3D culture, accompanied by reduced deposition of collagen I and IV. We also found that knockdown of P4HA2 inhibited mammary tumor growth and metastasis to lungs in xenograft models. Conclusion These results suggest the critical role of P4HA2 in breast cancer progression and identify P4HA2 as a potential therapeutic target and biomarker for breast cancer progression.
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            Multifunctional yolk-shell nanoparticles: a potential MRI contrast and anticancer agent.

            We report a new type of multifunctional nanomaterials, FePt@Fe2O3 yolk-shell nanoparticles, that exhibit high cytotoxicity originated from the FePt yolks and strong MR contrast enhancement resulting from the Fe2O3 shells. Encouraged by the recently observed high cytotoxicity of FePt@CoS2 yolk-shell nanoparticles, we used Fe2O3 to replace CoS2 as the shells to further explore the applications of the yolk-shell nanostructures. The ultralow IC50 value (238 +/- 9 ng of Pt/mL) of FePt@Fe2O3 yolk-shell nanoparticles likely originates from the fact that the slow oxidation and release of FePt yolks increases the cytotoxicity. Moreover, compared with two commercial magnetic resonance imaging (MRI) contrast agents, MION and Sinerem, the FePt@Fe2O3 yolk-shell nanoparticle showed stronger contrast enhancement according to their apparent transverse relaxivity values (r2* = 3.462 (microg/mL)(-1) s(-1)). The bifunctional FePt@Fe2O3 yolk-shell nanoparticles may serve both as an MRI contrast agent and as a potent anticancer drug. This work indicates that these unique yolk-shell nanoparticles may ultimately lead to new designs of multifunctional nanostructures for nanomedicine.
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              Designing an exercise intervention for adult survivors of childhood cancers

              Background This study examined current physical activity levels and preferences for exercise settings and activities among adult survivors of childhood cancers as a strategy to inform the feasibility and design of such programs. Methods A mixed-methods design was used to investigate current activity levels as well as barriers to and preferences for physical activity among 20 adult survivors of pediatric cancer. Results One-half of participants reported engaging in regular physical activity, although the frequency, intensity, and duration varied. Overall, 17 of the 20 participants (85%) stated they would be interested in participating in a structured exercise intervention, and they expressed a strong interest in walking (76%), bicycling (53%), and weight training (53%). Common barriers to participation in a potential structured exercise program were insufficient time, current health issues, and program location/distance. Nearly all participants agreed that information on nutrition and diet should be included as part of an exercise intervention. Conclusions These findings will help inform the design and implementation of future exercise programs to enhance physical activity among this high-risk group of cancer survivors. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-020-07763-8.
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                Author and article information

                Contributors
                chencl@tmu.edu.tw
                dhwei@ntut.edu.tw
                mhsiao@gate.sinica.edu.tw
                Journal
                J Nanobiotechnology
                J Nanobiotechnology
                Journal of Nanobiotechnology
                BioMed Central (London )
                1477-3155
                9 October 2021
                9 October 2021
                2021
                : 19
                : 308
                Affiliations
                [1 ]GRID grid.28665.3f, ISNI 0000 0001 2287 1366, Genomics Research Center, , Academia Sinica, ; Taipei, 115 Taiwan
                [2 ]GRID grid.262986.1, ISNI 0000 0004 0391 3307, Department of Chemistry, , Saint Michael’s College, ; Colchester, VT 05439 USA
                [3 ]GRID grid.412087.8, ISNI 0000 0001 0001 3889, Graduate Institute of Manufacturing Technology and Department of Mechanical Engineering, , National Taipei University of Technology, National Taipei University of Technology, ; Taipei, 106 Taiwan
                [4 ]GRID grid.260539.b, ISNI 0000 0001 2059 7017, Department of Biomedical Imaging and Radiological Sciences, , National Yang Ming Chiao Tung University, ; Taipei, 112 Taiwan
                [5 ]GRID grid.412897.1, ISNI 0000 0004 0639 0994, Department of Pathology, College of Medicine, Department of Pathology, , Taipei Medical University, Taipei Medical University Hospital, ; Taipei, 110 Taiwan
                [6 ]GRID grid.412019.f, ISNI 0000 0000 9476 5696, Department of Biochemistry, College of Medicine, , Kaohsiung Medical University, ; Kaohsiung, 807 Taiwan
                Author information
                http://orcid.org/0000-0001-8529-9213
                Article
                1052
                10.1186/s12951-021-01052-7
                8501633
                34627267
                505f02e2-2c34-44ab-b0d5-bd3ff1980f79
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 18 July 2021
                : 20 September 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004663, ministry of science and technology, taiwan;
                Award ID: MOST 110-2731-M-027-001
                Award ID: MOST 108-2628-E-027-002-MY3
                Award ID: MOST 109-2320-B-038-033
                Award Recipient :
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                Research
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                © The Author(s) 2021

                Biotechnology
                t2-weighted magnetic resonance imaging,superparamagnetic fept nanoparticles,hepatocellular carcinoma,drug delivery system,nanocomposites

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