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      NIR responsive tumor vaccine in situ for photothermal ablation and chemotherapy to trigger robust antitumor immune responses

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          Abstract

          Background

          Therapeutic tumor vaccine (TTV) that induces tumor-specific immunity has enormous potentials in tumor treatment, but high heterogeneity and poor immunogenicity of tumor seriously impair its clinical efficacy. Herein, a novel NIR responsive tumor vaccine in situ (HA-PDA@IQ/DOX HG) was prepared by integrating hyaluronic acid functionalized polydopamine nanoparticles (HA-PDA NPs) with immune adjuvants (Imiquimod, IQ) and doxorubicin (DOX) into thermal-sensitive hydrogel.

          Results

          HA-PDA@IQ NPs with high photothermal conversion efficiency (41.2%) and T 1-relaxation efficiency were using HA as stabilizer by the one-pot oxidative polymerization. Then, HA-PDA@IQ loaded DOX via π-π stacking and mixed with thermal-sensitive hydrogel to form the HA-PDA@IQ/DOX HG. The hydrogel-confined delivery mode endowed HA-PDA@IQ/DOX NPs with multiple photothermal ablation performance once injection upon NIR irradiation due to the prolonged retention in tumor site. More importantly, this mode enabled HA-PDA@IQ/DOX NPs to promote the DC maturation, memory T cells in lymphatic node as well as cytotoxic T lymphocytes in spleen.

          Conclusion

          Taken together, the HA-PDA@IQ/DOX HG could be served as a theranostic tumor vaccine for complete photothermal ablation to trigger robust antitumor immune responses.

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          Most cited references41

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          Dopamine-melanin colloidal nanospheres: an efficient near-infrared photothermal therapeutic agent for in vivo cancer therapy.

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            Radiotherapy and immunotherapy: a beneficial liaison?

            The interaction between radiotherapy and the host immune system has uncovered new mechanisms that can be exploited to improve the efficacy of radiotherapy. In this article, the authors highlight data providing new explanations for the success or failure of radiotherapy, and postulate, using radiation-induced tumour equilibrium (RITE) as an example, how the combination of immune-modulation and radiation could tip the balance of the host immune response to promote cure.
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              Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy

              A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours.
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                Author and article information

                Contributors
                1000003928@ujs.edu.cn
                biodfy@ujs.edu.cn
                Journal
                J Nanobiotechnology
                J Nanobiotechnology
                Journal of Nanobiotechnology
                BioMed Central (London )
                1477-3155
                17 May 2021
                17 May 2021
                2021
                : 19
                : 142
                Affiliations
                [1 ]GRID grid.452247.2, Department of Radiology, , Affiliated Hospital of Jiangsu University, ; Zhenjiang, People’s Republic of China
                [2 ]GRID grid.440785.a, ISNI 0000 0001 0743 511X, School of Medicine, , Jiangsu University, ; Zhenjiang, Jiangsu People’s Republic of China
                [3 ]The Third People’s Hospital of Changzhou, Changzhou, People’s Republic of China
                Author information
                http://orcid.org/0000-0002-3555-421X
                Article
                880
                10.1186/s12951-021-00880-x
                8130144
                34001148
                02f64ea9-8d9a-45b6-a5fa-e9de1e6f91ff
                © 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
                : 4 February 2021
                : 3 May 2021
                Funding
                Funded by: Natural Science Foundation of Jiangsu Province
                Award ID: SBK2020022937
                Award ID: BK20161317
                Award Recipient :
                Funded by: Key talents of young medicine in Jiangsu Province
                Award ID: QNRC2016444
                Award Recipient :
                Funded by: Six Talent Peaks Project in Jiangsu Province (CN)
                Award ID: No: WSN-281
                Award Recipient :
                Funded by: Zhenjiang key research and development plan
                Award ID: SH2019002
                Award Recipient :
                Funded by: Major natural science research projects of colleges and universities in Jiangsu province
                Award ID: 19KJA150004
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2021

                Biotechnology
                polydopamine nanoparticle,hyaluronic acid,photothermal therapy,immune therapy
                Biotechnology
                polydopamine nanoparticle, hyaluronic acid, photothermal therapy, immune therapy

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