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      Cancer nanomedicine

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          Abstract

          The field of cancer nanomedicine seeks to overcome the inherent shortcomings of conventional cancer diagnostics and therapies. Yet despite the surge of interest in and attractive attributes of nanotechnologies, challenges remain in their clinical translation, prompting some to argue that they have not yet reached their true potential. In this Viewpoint article, we asked four experts for their opinions on how we can fulfil the great promise of nanomedicine for the detection, diagnosis and treatment of patients with cancer.

          Abstract

          In this Viewpoint article, we asked four scientists working in the field of cancer nanomedicine to provide their opinions on how we can truly fulfil the great promise of nanotechnologies for the detection, diagnosis and treatment of patients with cancer.

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          Most cited references39

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          Engineering precision nanoparticles for drug delivery

          In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers — systemic, microenvironmental and cellular — that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-size-fits-all solution. As lipid-based, polymeric and inorganic nanoparticles are engineered in increasingly specified ways, they can begin to be optimized for drug delivery in a more personalized manner, entering the era of precision medicine. In this Review, we discuss advanced nanoparticle designs utilized in both non-personalized and precision applications that could be applied to improve precision therapies. We focus on advances in nanoparticle design that overcome heterogeneous barriers to delivery, arguing that intelligent nanoparticle design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.
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            Selective ORgan Targeting (SORT) nanoparticles for tissue specific mRNA delivery and CRISPR/Cas gene editing

            CRISPR/Cas gene editing and messenger RNA (mRNA)-based protein replacement therapy hold tremendous potential to effectively treat disease-causing mutations with diverse cellular origin. However, it is currently impossible to rationally design nanoparticles that selectively target specific tissues. Here, we report a strategy termed Selective ORgan Targeting (SORT) wherein multiple classes of lipid nanoparticles (LNPs) are systematically engineered to exclusively edit extrahepatic tissues via addition of a supplemental SORT molecule. Lung-, spleen-, and liver-targeted SORT LNPs were designed to selectively edit therapeutically relevant cell types including epithelial cells, endothelial cells, B cells, T cells, and hepatocytes. SORT is compatible with multiple gene editing techniques, including mRNA, Cas9 mRNA / sgRNA, and Cas9 ribonucleoprotein (RNP) complexes, and is envisioned to aid development of protein replacement and gene correction therapeutics in targeted tissues.
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              Nanotechnology for Multimodal Synergistic Cancer Therapy.

              The complexity, diversity, and heterogeneity of tumors seriously undermine the therapeutic potential of treatment. Therefore, the current trend in clinical research has gradually shifted from a focus on monotherapy to combination therapy for enhanced treatment efficacy. More importantly, the cooperative enhancement interactions between several types of monotherapy contribute to the naissance of multimodal synergistic therapy, which results in remarkable superadditive (namely "1 + 1 > 2") effects, stronger than any single therapy or their theoretical combination. In this review, state-of-the-art studies concerning recent advances in nanotechnology-mediated multimodal synergistic therapy will be systematically discussed, with an emphasis on the construction of multifunctional nanomaterials for realizing bimodal and trimodal synergistic therapy as well as the intensive exploration of the underlying synergistic mechanisms for explaining the significant improvements in synergistic therapeutic outcome. Furthermore, the featured applications of multimodal synergistic therapy in overcoming tumor multidrug resistance, hypoxia, and metastasis will also be discussed in detail, which may provide new ways for the efficient regression and even elimination of drug resistant, hypoxic solid, or distant metastatic tumors. Finally, some design tips for multifunctional nanomaterials and an outlook on the future development of multimodal synergistic therapy will be provided, highlighting key scientific issues and technical challenges and requiring remediation to accelerate clinical translation.
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                Author and article information

                Contributors
                sbhatia@mit.edu
                chen.shawn@nus.edu.sg
                marina@mail.nih.gov
                tlammers@ukaachen.de
                Journal
                Nat Rev Cancer
                Nat Rev Cancer
                Nature Reviews. Cancer
                Nature Publishing Group UK (London )
                1474-175X
                1474-1768
                8 August 2022
                : 1-7
                Affiliations
                [1 ]GRID grid.116068.8, ISNI 0000 0001 2341 2786, Institute for Medical Engineering and Science, , Massachusetts Institute of Technology, ; Cambridge, MA USA
                [2 ]GRID grid.116068.8, ISNI 0000 0001 2341 2786, Electrical Engineering and Computer Science, , Massachusetts Institute of Technology, ; Cambridge, MA USA
                [3 ]GRID grid.116068.8, ISNI 0000 0001 2341 2786, Koch Institute for Integrative Cancer Research, , Massachusetts Institute of Technology, ; Cambridge, MA USA
                [4 ]GRID grid.38142.3c, ISNI 000000041936754X, Department of Medicine, , Brigham and Women’s Hospital and Harvard Medical School, ; Boston, MA USA
                [5 ]GRID grid.413575.1, ISNI 0000 0001 2167 1581, Howard Hughes Medical Institute, ; Chevy Chase, MD USA
                [6 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, Department of Diagnostic Radiology, Yong Loo Lin School of Medicine and Faculty of Engineering, , National University of Singapore, ; Singapore, Singapore
                [7 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, Department of Surgery, Yong Loo Lin School of Medicine and Faculty of Engineering, , National University of Singapore, ; Singapore, Singapore
                [8 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, Department of Chemical and Biomolecular Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, , National University of Singapore, ; Singapore, Singapore
                [9 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, Department of Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, , National University of Singapore, ; Singapore, Singapore
                [10 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, , National University of Singapore, ; Singapore, Singapore
                [11 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, , National University of Singapore, ; Singapore, Singapore
                [12 ]GRID grid.418021.e, ISNI 0000 0004 0535 8394, Nanotechnology Characterization Laboratory, Cancer Research Technology Program, , Frederick National Laboratory for Cancer Research, ; Frederick, MD USA
                [13 ]GRID grid.1957.a, ISNI 0000 0001 0728 696X, Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging (ExMI), Center for Biohybrid Medical Systems (CBMS), , RWTH Aachen University Clinic, ; Aachen, Germany
                Author information
                http://orcid.org/0000-0002-1293-2097
                http://orcid.org/0000-0002-9622-0870
                http://orcid.org/0000-0002-4233-9227
                http://orcid.org/0000-0002-1090-6805
                Article
                496
                10.1038/s41568-022-00496-9
                9358926
                35941223
                bc5f81ce-008a-4e46-bf0a-1ffc5b17148a
                © Springer Nature Limited 2022

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 27 June 2022
                Categories
                Viewpoint

                cancer therapy,cancer imaging,nanomedicine
                cancer therapy, cancer imaging, nanomedicine

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