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      Iodine loaded nanoparticles with commercial applicability increase survival in mice cancer models with low degree of side effects

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          Abstract

          Background

          The recorded use of iodine in medicine, dates to 5000 BC. Molecular iodine (I 2) has been claimed to exert an antineoplastic effect that triggers apoptotic and re‐differentiation mechanisms in different types of cancer cells in animal studies. Hitherto, all experiments published have been carried out with I 2 diluted in water preparations resulting in the administration of ionized iodide, either alone or in combination with low levels of I 2. To maximize the levels of I 2 by avoiding water solutions we have managed to develop a colloidal nano particle (NP) loaded with I 2 with a Z‐average of 7‐23 nm with remarkable stability, preferable osmolality and commercial applicability.

          Aims

          Here we report the results from formulation and pre‐clinical studies with the rationale: a) to find a tolerable dose of the I 2 NP system delivered intravenously or per‐orally, and b) to determine if the tolerable doses are efficacious in murine models of cancer.

          Methods and Results

          A novel drug delivery system with I 2 NP was formulated and murine cancer models with CT26, MDA‐MB‐231 and LL/2 cells were used to analyse the efficacy. Despite the formulation challenges we were successful in constructing stable NPs loaded with I 2 which have convincing commercial applicability. We conclude that administration of the NP I 2 drug delivery system: 1. Blunted tumour growth in a xenograft breast cancer model; 2. Had a significant effect on survival in the orthotopic, syngeneic lung metastasis model; 3. Showed reduced tumour burden in post‐mortem evaluation and; 4. Was associated with low degree of side effects.

          Conclusions

          Taken all together, our findings indicate that the NP I 2 drug delivery system may serve as a novel effective cancer treatment with low degree of side effects. This is something which needs further exploration including confirmation in future clinical trials.

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          Most cited references17

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          Povidone‐iodine ointment demonstrates in vitro efficacy against biofilm formation

          Abstract Anti‐infectives used to treat chronic exuding wounds are diluted by wound exudates, absorbed into dressings, metabolised by proteases and destroyed by pH. In order to mimic such effects of exudates, the efficacy of six topical wound agents was assessed undiluted and at 10% concentrations, including povidone‐iodine ointment and a silver‐impregnated wound dressing, to remove biofilms of Pseudomonas aeruginosa, multi‐species biofilms of Candida albicans and methicillin‐resistant Staphylococcus aureus (MRSA) in vitro in a Centers for Disease Control and Prevention (CDC) reactor. Povidone‐iodine was also diluted to 3·3% and 33·3% of the commercial concentrations. Viable microorganisms in each preparation were quantified by colony count. No viable P. aeruginosa biofilm material was recovered after 4 and 24 hours of treatment with povidone‐iodine ointment at the 100% and 10% concentrations. No C. albicans/MRSA biofilm material was recovered after 4 and 24 hours of treatment with povidone‐iodine ointment at the 100% concentration. In general, following dilution, povidone‐iodine ointment appeared to exhibit greater biofilm removal than the other agents tested. Further research involving different microorganisms in vitro and in vivo over a longer period of time will help elucidate the full potential of povidone‐iodine ointment and liposomal hydrogel.
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            A Role for Iodide and Thyroglobulin in Modulating the Function of Human Immune Cells

            Iodine is an essential element required for the function of all organ systems. Although the importance of iodine in thyroid hormone synthesis and reproduction is well known, its direct effects on the immune system are elusive. Human leukocytes expressed mRNA of iodide transporters (NIS and PENDRIN) and thyroid-related proteins [thyroglobulin (TG) and thyroid peroxidase (TPO)]. The mRNA levels of PENDRIN and TPO were increased whereas TG transcripts were decreased post leukocyte activation. Flow cytometric analysis revealed that both PENDRIN and NIS were expressed on the surface of leukocyte subsets with the highest expression occurring on monocytes and granulocytes. Treatment of leukocytes with sodium iodide (NaI) resulted in significant changes in immunity-related transcriptome with an emphasis on increased chemokine expression as probed with targeted RNASeq. Similarly, treatment of leukocytes with NaI or Lugol’s iodine induced increased protein production of both pro- and anti-inflammatory cytokines. These alterations were not attributed to iodide-induced de novo thyroid hormone synthesis. However, upon incubation with thyroid-derived TG, primary human leukocytes but not Jurkat T cells released thyroxine and triiodothyronine indicating that immune cells could potentially influence thyroid hormone balance. Overall, our studies reveal the novel network between human immune cells and thyroid-related molecules and highlight the importance of iodine in regulating the function of human immune cells.
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              Nanoengineered delivery systems for cancer imaging and therapy: recent advances, future directions and patent evaluation

              Cancer is the second highest cause of death worldwide. Several therapeutic approaches, such as conventional chemotherapy, antibodies and small molecule inhibitors and nanotherapeutics have been employed in battling cancer. Amongst them, nanotheranostics is an example of successful personalized medicine bearing dual role of early diagnosis and therapy to cancer patients. In this review, we have focused on various types of theranostic polymer and metal nanoparticles for their role in cancer therapy and imaging concerning their limitation, future application such as dendritic cell cancer vaccination, gene delivery, T-cell activation and immune modulation. Also, some of the recorded patent applications and clinical trials have been illustrated. The impact of the biological microenvironment on the biodistribution and accumulation of nanoparticles have been discussed.
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                Author and article information

                Contributors
                torkel.falkenberg@ki.se
                Journal
                Cancer Rep (Hoboken)
                Cancer Rep (Hoboken)
                10.1002/(ISSN)2573-8348
                CNR2
                Cancer Reports
                John Wiley and Sons Inc. (Hoboken )
                2573-8348
                02 June 2023
                August 2023
                : 6
                : 8 ( doiID: 10.1002/cnr2.v6.8 )
                : e1843
                Affiliations
                [ 1 ] Department of Neurobiology, Care Sciences and Society Karolinska Institutet Stockholm Sweden
                [ 2 ] Torfal AB, A Working Lab, Innomedicum Karolinska Institutet Science Park Solna Sweden
                [ 3 ] Adlego Biomedical AB Solna Sweden
                [ 4 ] SDS Life Science Stockholm Sweden
                [ 5 ] Shigeru AG Basel Switzerland
                Author notes
                [*] [* ] Correspondence

                Torkel Falkenberg, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

                Email: torkel.falkenberg@ 123456ki.se

                Author information
                https://orcid.org/0000-0002-8150-9380
                Article
                CNR21843
                10.1002/cnr2.1843
                10432436
                37269144
                6628ac7f-9b77-4765-9bf4-9f648e0b5371
                © 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 May 2023
                : 06 March 2023
                : 22 May 2023
                Page count
                Figures: 7, Tables: 6, Pages: 12, Words: 6409
                Funding
                Funded by: Shigeru AG, Switzerland
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                August 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.3 mode:remove_FC converted:16.08.2023

                cytotoxic,drug delivery,molecular iodine,nanoparticles,side effects

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