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WIREs Nanomed Nanobiotechnol
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Rational design of nanomedicine for photothermal‐chemodynamic bimodal cancer therapy

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Abstract Given the diversity, complexity, and heterogeneity of persistent tumors, traditional nanoscale monotherapeutic systems suffer from dissatisfactory curative efficiency with incidence of metastasis or relapse. In parallel, the trend of clinical research on the basis of nanomedicines has increasingly shifted from monotherapy toward combinatorial therapy for admirable synergetic performances. In this regard, cutting‐edge nanomedicines harnessing photothermal‐chemodynamic bimodal therapy (PTT/CDT) have opened up a highly‐efficient and relatively‐safe cancer theranostic paradigm. Still, the integration of PTT/CDT functional units into one nanomedicine remains a herculean but meaningful task to achieve notable super‐additive effects. This review aims to elucidate underlying synergistic interactions of PTT/CDT and highlight intriguing designs of nanomedicines for PTT/CDT including nanomaterial selection, performance optimization, multimodal therapy, visualization strategies, and targeting strategies. Furthermore, an outlook on further improvements of PTT/CDT is provided, emphasizing significant scientific issues that require remediation for clinical translation. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Potential synergistic mechanisms of PTT/CDT
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(a) Scheme of the cancer therapy of TTIS nanocomposite. (b) Body weights of mice in diverse groups (TNIS, tumor nontargeting iron sponge). (c) Tumor growth curves in diverse groups. (d) Average weight of the tumors after diverse treatments. (e) H&E staining after various treatments. (f) Scheme of the cancer therapy of FeS2@C‐TA‐GOx‐FA. (g) Element mapping of Fe3S4 tetragonal nanosheets. (h) Biodistribution of Fe in major organs and tumors 6 and 12 hr after intravenous injection under magnetic targeting. (Reprinted with permission from Min et al. (2020). Copyright 2020, WILEY‐VCH; Wu et al. (2020). Copyright 2020, American Chemical Society; G. Guan et al. (2018). Copyright 2018, Elsevier)
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(a) Scheme of the synthetic process and cancer therapy of [email protected] nanostructures. (b) Probably cellular response after treatment. (c) MIP PET images of mice. (d) Schematic of the cancer therapy of FeOCl NRs based NPs. (e) TEM images, size distribution, and STEM‐EDS mapping images of TOPY‐PEG NSs. (f) Fluorescence images of mice. (Reprinted with permission from K. Hu et al. (2020). Copyright 2020, Springer Nature Limited; M. Zhang, Sheng, et al. (2020). Copyright 2020, Elsevier; Wilson et al. (2020). Copyright 2020, WILEY‐VCH)
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(a) Scheme of the cancer therapy of [email protected] NSs. (b) T1‐weighted MR images of mice. (c) T1‐weighted MR images of tumors. (d) Schematic of the degradation of Bi2S3‐MnO2 NPs. (e) PA images after diverse treatments. (f) Scheme of the cancer therapy of Au2Pt‐PEG‐Ce6 nanomedicine. (g) 3D reconstructed CT images of mice. (Reprinted with permission from Z. H. Zhao et al. (2019). Copyright 2019, Elsevier; Zheng et al. (2020). Copyright 2020, The Royal Society of Chemistry; M. Wang, Chang, et al. (2020). Copyright 2020, Elsevier)
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(a) Scheme of the synthetic process and cancer therapy of CFNs. (b) Scheme of the synthetic process of Fe (III)@WS2 nanocapsules. (c) Scheme of the cancer therapy of BSO‐FeS2 NPs. (d) Scheme of the multimode cancer therapy of Cu2MoS4. (e) The flow cytometric analyses of CD4+ T cells. (Reprinted with permission from Y. Liu, Zhen, et al. (2018). Copyright 2018, American Chemical Society; C. Y. Wu, Wang, et al., 2019. Copyright 2019, WILEY‐VCH; Xiao et al. (2020). Copyright 2020, Elsevier; G. Gao et al. (2019). Copyright 2019, WILEY‐VCH)
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(a) Scheme of the synthetic process and cancer therapy of [email protected]‐100 nanoreactors. (b) UV‐vis absorbance of diverse groups. (c) The GSH‐depletion after diverse treatments. (d) Schematic illustration of Mn2+ release. (e) Released Mn2+ percent after diverse treatments. (f) Scheme of the cancer therapy of Fe‐GA/CaO2@PCM nanomedicine. (g) H2O2 generation in different groups. (h) MB degradation caused by •OH under different conditions. (Reprinted with permission from F. Liu, Lin, et al. (2019). Copyright 2019, WILEY‐VCH; Duan et al. (2020). Copyright 2020, Elsevier; S. C. Zhang, Cao, et al. (2020). Copyright 2020, American Chemical Society)
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(a) Scheme of the synthetic process and cancer therapy of FP NRs. (b) NIR thermal images of FP NRs in vivo. (c) Tumor photographs and H&E stating after diverse treatments. (d) Schematic of diverse Cu9S8 NPs. (e) ESR spectra of diverse Cu9S8 NPs. (f) Scheme of the cancer therapy of the nanomedicine composed of CuS NPs, iron‐containing molecules, and thermosensitive polymers. (g) Photothermal properties under diverse NIR irradiation (Left: 808 nm; Right: 980 nm). (h) RhB degradation and ESR spectra by the Fenton reaction. (Reprinted with permission from Y. Liu, Zhen, et al. (2019). Copyright 2019, WILEY‐VCH; Wang, An, Lin, et al. (2020). Copyright 2020, Elsevier; Nie et al. (2019). Copyright 2019, American Chemical Society)
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(a) Scheme of the synthetic process and cancer therapy of Cu2 − xSe‐Au Janus NPs. (b) TEM images of Cu2 − xSe‐Au Janus NPs. (c) Scheme of [email protected]2 core‐shell nanoplatform mediated cancer therapy. (d) Scheme of the synthetic process of [email protected] (Reprinted with permission from Y. Wang, Li, et al. (2020). Copyright 2020, Elsevier; H. Wang, An, Tao, et al. (2020). Copyright 2020, The Royal Society of Chemistry; Fan et al. (2018). Copyright 2018, American Chemical Society)
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(a) Scheme of FeS2 NPs mediated cancer therapy. (b) 4 T1 cell growth inhibition after various treatments. (c) TEM image, HRTEM image, selected area electron diffraction pattern, HAADFSTEM, and element mapping of CP NCs. (d) CCK‐8 assay of HeLa cells with various treatments. (e) Scheme of the synergetic therapy of WO3 − x NPs. (f) Photothermal properties of WO3 − x NPs with various concentrations. (g) Scheme of the synthetic process and cancer therapy of Mo‐POM. (Reprinted with permission from Tang et al. (2017). Copyright 2017, WILEY‐VCH; Y. Liu, Wu, et al. (2019). Copyright 2019, WILEY‐VCH; P. Liu, Wang, et al. (2018). Copyright 2018, American Chemical Society; G. Liu, Zhu, et al. (2019). Copyright 2019, Wiley‐VCH)
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Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

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