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WIREs Nanomed Nanobiotechnol
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Recent advances in photodynamic therapy for cancer and infectious diseases

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Abstract Photodynamic therapy (PDT) is a treatment by combining light and a photosensitizer to generate reactive oxygen species (ROS) for cellular damage, and is used to treat cancer and infectious diseases. In this review, we focus on recent advances in design of new photosensitizers for increased production of ROS and in genetic engineering of biological photosensitizers to study cellular signaling pathways. A new concept has been proposed that PDT‐induced acute inflammation can mediate neutrophil infiltration to deliver therapeutics in deep tumor tissues. Combination of PDT and immunotherapies (neutrophil‐mediated therapeutic delivery) has shown the promising translation of PDT for cancer therapies. Furthermore, a new area in PDT is to treat bacterial infections to overcome the antimicrobial resistance. Finally, we have discussed the new directions of PDT for therapies of cancer and infectious diseases. In summary, we believe that rational design and innovations in nanomaterials may have a great impact on translation of PDT in cancer and infectious diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
(a) Concept and structure of RET‐BDP‐TNM. (b) Absorption spectra of donor moiety B‐1, acceptor moiety B‐2, and RET‐BDP. (c) Fluorescence emission spectra of donor moiety B‐1, acceptor moiety B‐2, and RET‐BDP upon excitation with 610 nm light. (d) The change of 1,3‐diphenylisobenzofuran (DPBF) optical density versus irradiation time for mixtures of DPBF with RET‐BDP‐TNM, B1‐TNM, and B2‐TNM, respectively, upon excitation with 645 nm light (10 mW/cm2). (e) PDT effect of RET‐BDP‐TNM in HeLa cells with PI staining for dead cells observed by confocal fluorescence microscopy. (f) ROS generation of RET‐BDP‐TNM in HeLa cells measured by DCFH‐DA. (g) Digital pictures of 4T1 tumors with different treatments. Scale bar represents 30 μm. (Reprinted with permission from L. Huang et al. (). Copyright 2017 John Wiley and Sons)
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(a) Synthetic process of copper ferrite nanospheres (CFNs) and their therapeutic mechanism. (Reprinted with permission from Liu et al. (). Copyright 2018 American Chemical Society). (b) Structure and synthetic processes for MitDt groups. (Reprinted with permission from Noh et al. (). Copyright 2018 Wiley‐VCH)
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Schematic diagrams show the components of semiconducting polymer nanoparticles (SPNs) doped with nanoceria and the concept of controllable photodynamic capacities of SPNs that are dependent on tissue microenvironments (a), and the differences between conventional photodynamic therapy (PDT) and self‐regulated PDT when nanoceria are doped in SPNs (b). (c) in vitro studies show the capabilities of ROS scavenging by SPNs. Fluorescence intensities of ROS indicator were measured after addition of SPNs doped with different amount of nanoceria. (d) in vitro ROS generation from SPNs. The fluorescence changes of ROS indicator mixed with SPN‐0 or SPN‐C23 in different pH conditions irradiated with laser at 808 nm (0.44 W/cm2) as a function of irradiation time. (e) The graph illustrates the different responses of ROS in SPN‐0 or SPN‐C23 after irradiated with NIR laser and ROS responses were measured by H2DCFDA. (f) Tumor growth after mice were treated with different drug formulations. (g) Histological H&E staining of mouse muscles 24 hr after the different treatments irradiated with NIR laser for 5 min. (Reprinted with permission from Zhu et al. (). Copyright 2017 American Chemical Society)
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Schematic illustration of the photochemical reactions in photodynamic therapy
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(a) Synthesis process of MoS2‐BNN6 and PTT/NO synergistic treatments for killing bacteria. (b) Field emission scanning electron microscopy (FE‐SEM) photographs of Ampr Escherichia coli (first and second lines) and Escherichia faecalis (third and fourth lines) with different indicated treatments. Red arrows indicate the broken sites of bacteria. (c) Wound area changes of mice with indicated treatments. (d) Body weight change of mice with different treatments. (Reprinted with permission from Q. Gao et al. (). Copyright 2018 John Wiley and Sons)
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(a) Measurements of PL intensity of TriPE‐NT in THF with different proportion of water. (b) Plotting of fluorescence intensity of DCFH with or without presence of TriPE‐NT irradiated with white light. (c) Survival rates of Escherichia coli wild type and MDR bacteria under different white light irradiation time treated with or without TriPE‐NT. (d) Survival rates of Staphylococcus epidermidis wild type and MDR bacteria under different white light irradiation time treated with or without TriPE‐NT. (e) The percentage of E. coli wild type and MDR bacteria‐infected wound area 3 or 7 days after surgery, with or without treatment of TriPE‐NT. (f) The percentage of S. epidermidis wild type and MDR bacteria‐infected wound area 3 or 7 days after surgery, with or without treatment of TriPE‐NT and irradiation. (#p < .001, .001 < *p < .05). (Reprinted with permission from Y. Li et al. (). Copyright 2018 John Wiley and Sons)
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(a) Contents of neutrophils in tumor tissue 24 or 48 hr after injection of PBS and TA99. Tumor samples were subjected to single cell suspension after treatments and measured by flow cytometry. (b) Neutrophils (green) uptake of albumin nanoparticles (red) with or without TA99 observed using fluorescence confocal microscopy. Nucleus was marked by DAPI (blue). (c) Contents of BSA NPs in tumor tissue with different indicated treatments, TA99 obviously increases the contents of albumin NPs in tumor tissue. Anti‐Gr‐1 antibody applied for depleting neutrophils. The measurements of (d) tumor volume, (e) survival rates of bearing melanoma mice illuminated with 660 nm laser under different treatments. Treatments include injection of vehicles, TA99, Ppa‐loaded NPs, or both of TA99 and Ppa‐loaded NPs, the effectiveness of PDT‐mediated cancer therapy has been confirmed, *p < .05, **p < .01. (Reprinted with permission from Chu et al. (). Copyright 2016 John Wiley and Sons)
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(a) Hypothesis illustration of nanoparticles (NPs) taken up by activated neutrophils to inflamed tumors induced by photosensitization. (b–e) Mouse tumors with different treatments observed using intravital microscopy. PS represents photosensitization (intravenous injection of Ppa followed by tumors irradiated with 660 nm laser). (f) Images of hyperthermia in mouse tumors with different treatments after photosensitization. (g) Temperature change of tumor versus irradiation time during photosensitization. (h) Tumor volume and (i) survival rate of the tumor‐bearing mice with different treatments. Data represent mean ± SD, **p < .01. (Reprinted with permission from Chu et al. (). Copyright 2017 John Wiley and Sons)
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(a) Hypothesis depiction of T‐TTD dots accumulation in tumor through passive and active targeting, and tumor ablation via PDT. (b) Fluorescent signal of T‐TTD dots (red) observed in QBC939 cells, while weak fluorescence of T‐TTD dots in L‐O2, and HK‐2 cells after incubation with T‐TTD dots (5 μg/mL) for 4 hr. Nuclei is labeled as blue and cytoskeleton is labeled as green. Scale bar represents 50 μm. (c) in vivo targeting ability of T‐TTD dots to tumor, after blocking the receptors, the tumor uptake of dots is significantly inhibited. (d) Tumor volume curve of mice with different treatments. Data represent mean ± SD; **p < .01. (Reprinted with permission from M. Li et al. (). Copyright 2017 American Chemical Society)
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(a) Schematic illustration of photosensitizing effect induced by FAP‐TAPs. (b) Cellular photoablation of FAP‐TAPs on HEK cells expressing TM‐dL5** and wild‐type HEK293 cells. Fluorescently labeled HEK cells were treated with MG‐2I, MG‐ester and nontargeted MG‐2I/ dL5** in the concentration of 400 nM for 30 min before illuminated with light (λex = 640 nm, 0.76 W/cm2, 1 min). After 30 min, live/dead cell viability was assayed. Scale bar represents 10 μm. (c) FAP‐TAPs demonstrate the damage to cardiac function and phenotype development of adult zebrafish expressed dL5** in the heart, photographs show the change in development of phenotype from 0 h.p.i. to 96 h.p.i. in wild‐type and dL5** expressed zebrafish with different treatments. Scale bar represents 1,000 μm. (Reprinted with permission from J. He et al. (). Copyright 2016 Springer Nature)
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(a) Structure of D–A‐type CP‐NPs. (b) Photophysical mechanism for dual PTT/PDT in cancer treatment using D–A‐type CP‐NPs. (c) The plot of temperature changes in CP‐NPs, AuNRs, and ICG‐M during repeatable irradiation/cooling cycles. (d) The plot of ROS production of CP‐NPs and ICG‐M during different irradiation time (λex = 785 nm, 1.5 W/cm2). (e) 1O2 generation in acridine orange (AO) stained 4T1 tumor cells treated with different concentrations of CP‐NPs with or without irradiation observed using confocal microscopy (scale bar represents 20 μm). (f) ROS generation in tumor of the mice stained by DHE under irradiation with different treatments (scale bar represents 100 μm). (g) Temperature elevation in tumor area (yellow circle) of the mice treated with different doses of CP‐NPs under irradiation. (h) Quantification of temperature elevation at tumor area of the mice treated with different doses of CP‐NPs under irradiation. (i) 4T1 tumor‐bearing mice survival rate with different treatments. (Reprinted with permission from Tao et al. (). Copyright 2017 John Wiley and Sons)
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Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease

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