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      Therapeutic applications of nanobiotechnology

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          Abstract

          Nanobiotechnology, as a novel and more specialized branch of science, has provided a number of nanostructures such as nanoparticles, by utilizing the methods, techniques, and protocols of other branches of science. Due to the unique features and physiobiological characteristics, these nanostructures or nanocarriers have provided vast methods and therapeutic techniques, against microbial infections and cancers and for tissue regeneration, tissue engineering, and immunotherapies, and for gene therapies, through drug delivery systems. However, reduced carrying capacity, abrupt and non-targeted delivery, and solubility of therapeutic agents, can affect the therapeutic applications of these biotechnological products. In this article, we explored and discussed the prominent nanobiotechnological methods and products such as nanocarriers, highlighted the features and challenges associated with these products, and attempted to conclude if available nanostructures offer any scope of improvement or enhancement. We aimed to identify and emphasize the nanobiotechnological methods and products, with greater prospect and capacity for therapeutic improvements and enhancements. We found that novel nanocarriers and nanostructures, such as nanocomposites, micelles, hydrogels, microneedles, and artificial cells, can address the associated challenges and inherited drawbacks, with help of conjugations, sustained and stimuli-responsive release, ligand binding, and targeted delivery. We recommend that nanobiotechnology, despite having few challenges and drawbacks, offers immense opportunities that can be harnessed in delivering quality therapeutics with precision and prediction. We also recommend that, by exploring the branched domains more rigorously, bottlenecks and obstacles can also be addressed and resolved in return.

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          Most cited references288

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          The blockade of immune checkpoints in cancer immunotherapy.

          Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
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            Cancer immunotherapy using checkpoint blockade

            The release of negative regulators of immune activation (immune checkpoints) that limit antitumor responses has resulted in unprecedented rates of long-lasting tumor responses in patients with a variety of cancers. This can be achieved by antibodies blocking the cytotoxic T lymphocyte antigen-4 (CTLA-4) or the programmed death-1 (PD-1) pathway, either alone or in combination. The main premise for inducing an immune response is the pre-existence of antitumor T cells that were limited by specific immune checkpoints. Most patients who have tumor responses maintain long lasting disease control, yet one third of patients relapse. Mechanisms of acquired resistance are currently poorly understood, but evidence points to alterations that converge on the antigen presentation and interferon gamma signaling pathways. New generation combinatorial therapies may overcome resistance mechanisms to immune checkpoint therapy.
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              Chimeric antigen receptor T cells for sustained remissions in leukemia.

              Relapsed acute lymphoblastic leukemia (ALL) is difficult to treat despite the availability of aggressive therapies. Chimeric antigen receptor-modified T cells targeting CD19 may overcome many limitations of conventional therapies and induce remission in patients with refractory disease. We infused autologous T cells transduced with a CD19-directed chimeric antigen receptor (CTL019) lentiviral vector in patients with relapsed or refractory ALL at doses of 0.76×10(6) to 20.6×10(6) CTL019 cells per kilogram of body weight. Patients were monitored for a response, toxic effects, and the expansion and persistence of circulating CTL019 T cells. A total of 30 children and adults received CTL019. Complete remission was achieved in 27 patients (90%), including 2 patients with blinatumomab-refractory disease and 15 who had undergone stem-cell transplantation. CTL019 cells proliferated in vivo and were detectable in the blood, bone marrow, and cerebrospinal fluid of patients who had a response. Sustained remission was achieved with a 6-month event-free survival rate of 67% (95% confidence interval [CI], 51 to 88) and an overall survival rate of 78% (95% CI, 65 to 95). At 6 months, the probability that a patient would have persistence of CTL019 was 68% (95% CI, 50 to 92) and the probability that a patient would have relapse-free B-cell aplasia was 73% (95% CI, 57 to 94). All the patients had the cytokine-release syndrome. Severe cytokine-release syndrome, which developed in 27% of the patients, was associated with a higher disease burden before infusion and was effectively treated with the anti-interleukin-6 receptor antibody tocilizumab. Chimeric antigen receptor-modified T-cell therapy against CD19 was effective in treating relapsed and refractory ALL. CTL019 was associated with a high remission rate, even among patients for whom stem-cell transplantation had failed, and durable remissions up to 24 months were observed. (Funded by Novartis and others; CART19 ClinicalTrials.gov numbers, NCT01626495 and NCT01029366.).
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                Author and article information

                Contributors
                yogeshkind@gmail.com
                ramendra.pandey@gmail.com
                mamtadental@gmail.com
                archana.g@srmuniversity.ac.in
                arpana.v@srmuniversity.ac.in
                jasmina.vidic@inrea.fr
                directorcd4@srmuniversity.ac.in
                cmchang@mail.cgu.edu.tw
                anjalipriyadarshini1@gmail.com
                Journal
                J Nanobiotechnology
                J Nanobiotechnology
                Journal of Nanobiotechnology
                BioMed Central (London )
                1477-3155
                6 May 2023
                6 May 2023
                2023
                : 21
                : 148
                Affiliations
                [1 ]GRID grid.473746.5, Department of Microbiology, , SRM University, ; 39, Rajiv Gandhi Education City, Post Office P.S. Rai, Sonepat, Haryana 131029 India
                [2 ]Mamta Dental Clinic, Opposite Sector 29, Main Badkhal Road, Faridabad, Haryana 121002 India
                [3 ]GRID grid.473746.5, Department of Biotechnology, , SRM University, ; 39, Rajiv Gandhi Education City, Post Office P.S. Rai, Sonepat, Haryana 131029 India
                [4 ]GRID grid.462293.8, ISNI 0000 0004 0522 0627, Université Paris-Saclay, Micalis Institute, INRAE, AgroParisTech, ; 78350 Jouy-en-Josas, France
                [5 ]GRID grid.145695.a, ISNI 0000 0004 1798 0922, Master & Ph.D Program in Biotechnology Industry, , Chang Gung University, ; No.259, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 33302 Taiwan (ROC)
                Article
                1909
                10.1186/s12951-023-01909-z
                10163736
                37149615
                ada31706-f55a-493e-bf20-994db3655605
                © The Author(s) 2023

                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
                : 28 February 2023
                : 24 April 2023
                Funding
                Funded by: Chang Gung University Taiwan
                Award ID: VtR Inc-CGU (SCRPD1L0221); DOXABIO-CGU (SCRPD1K0131), and CGU grant (UZRPD1L0011, UZRPD1M0081).
                Award Recipient :
                Categories
                Review
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                © BioMed Central Ltd., part of Springer Nature 2023

                Biotechnology
                nanobiotechnology,nanoparticles,anticancer agents,wound healing,tissue regeneration
                Biotechnology
                nanobiotechnology, nanoparticles, anticancer agents, wound healing, tissue regeneration

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