Combination of photodynamic therapy and immunomodulation: Current status and future trends

Qiang, Yong-Gang; Yow, Cmn; Huang, Zheng

doi:10.1002/med.20121

Cited by 55 publications

(44 citation statements)

References 77 publications

(78 reference statements)

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“…2 Photodynamic therapy (PDT) has been used to treat cardiovascular pathologies, including AS and restenosis, [3][4][5] which produces reactive oxygen species (ROS) and photo-induced biological damage according to the principle of energy transfer from light to a photosensitizer in tissues. 6 However, because of its poor tissue penetration, PDT is limited to superficial lesions. Fortunately, an alternative therapy exists: low-intensity ultrasound can penetrate deeply into tissues due to its much lower attenuation coefficient in tissues compared with lasers.…”

Section: Introductionmentioning

confidence: 99%

The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages

Li¹,

Gao²,

Zheng³

et al. 2015

IJN

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Purpose To investigate the sonoactivity of hypericin (HY), together with its sonodynamic effect on THP-1 macrophages and the underlying mechanism. Materials and methods CCK-8 was used to examine cell viability. Confocal laser scanning microscopy was performed to assess the localization of HY in cells, reactive oxygen species (ROS) generation, and opening of the mitochondrial permeability transition pore (mPTP) after different treatments. Apoptosis was analyzed using Hoechst–propidium iodide and transmission electron microscopy. Mitochondrial membrane potential (ΔΨm) collapse was detected via fluorescence microscopy. Lipoprotein oxidation was determined in malondialdehyde (MDA) assays. Western blotting was conducted to determine the translocation of BAX and cytochrome C and the expression of apoptosis-related proteins. Results HY was sublocalized among the nuclei and the mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosome in the cytosol of THP-1 macrophages. Under low-intensity ultrasound irradiation, HY significantly decreased cell viability and induced apoptosis. Furthermore, greater ROS generation, higher MDA levels, and greater ΔΨm loss were observed in the sonodynamic therapy (SDT) group. Both ROS generation and MDA levels were significantly reduced by the ROS scavenger N-acetyl cysteine (NAC) and the singlet oxygen scavenger sodium azide. Most of the loss of ΔΨm was inhibited by pretreatment with NAC, sodium azide, and the mPTP inhibitor cyclosporin A (CsA). mPTP opening was induced upon SDT but was reduced by pretreatment with bongkrekic acid, 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid disodium, CsA, and NAC. Western blot analyses revealed translocation of BAX and cytochrome C, downregulated expression of Bcl-2, and upregulated expression of cleaved caspase-9, cleaved caspase-3, and cleaved poly(ADP-ribose) polymerase in the SDT group, which were reversed by NAC. Conclusion HY mediated SDT-induced apoptosis in THP-1 macrophages via ROS generation. Then, the proapoptotic factor BAX translocated from the cytosol to the mitochondria, increasing the ratio of BAX/Bcl-2, and the mPTP opened to release cytochrome C. This study demonstrated the great potential of HY-mediated SDT for treating atherosclerosis.

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Section: Introductionmentioning

confidence: 99%

The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages

Li¹,

Gao²,

Zheng³

et al. 2015

IJN

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“…Details of the results obtained in the about 250 clinical trials officially reported for PDT can be found in recent reviews [139]. Thus, the conclusion can be safely accepted that PDT represents a reasonable option, sometimes even as a primary treatment, in the oncological field, even though caution still exists owing to the limited number of adequately randomized trials carried out by the various centers [140].…”

Section: Clinical Indications For Pdtmentioning

confidence: 83%

Basic and Clinical Aspects of Photodynamic Therapy

Rapozzi

Jori

2014

Resistance to Targeted Anti-Cancer Therapeutics

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Photodynamic therapy (PDT) was originally developed for the treatment of solid tumors by the concerted action of a tumor-localizing agent, named as the photosensitizer, molecular oxygen and visible light source. The photoinduced cytotxic species are mainly represented by singlet oxygen ( 1 O 2 ), even though the formation of NO has been observed in selected situations. Optimal results are generally obtained by using porphyrins and their tetrapyrrolic analogues as the photodynamic agents, since these compounds display an intense absorbance of the red spectra wavelengths, which are endowed with a particularly deep penetration into most biological tissues. While several porphyrins exhibit an intrinsic preferential affinity for malignant tissues, the selectivity of the tumor localization can be significantly enhanced by pre-binding the photosensitizer with a targeting agent, such as an antibody or a vehicle (e.g., glycoproteins, peptides, oligonucleotide aptamers, growth factors, lipoproteins) directed against antigens or receptors which are specifically present at the surface of tumor cells. Recently, novel perspectives have been opened by the association of the photosensitizer with nanoparticles, which can be made to be multifunctional, thereby allowing the simultaneous delivery of photoactivatable moieties acting by different mechanisms, as well as of phototherapeutic and photodiagnostic agents. The chemical structure of the photosensitizer and the nature of the possible carrier have important consequences with regards to the distribution of the photosensitizer among different compartments of the tumor tissue, such as neoplastic cells, blood vessels or the non-vascular stroma, as well as its localization in different subcellular sites; these would obviously affect the mechanism of photoinduced tumor damage, modulating the competition between necrosis, apoptosis and autophagia, the importance of photoinduced hypoxia, and the balance between enhancement of the immune response and immunosuppression. So far, about 250 randomized clinical trials have been officially reported for 4 V. Rapozzi and G. Jori PDT of tumors, and essentially all types of solid tumors with the exception of melanotic melanoma have been found to be positively responsive to the photodynamic treatment. Thus, PDT is currently considered as a reasonable option for the treatment of a variety of malignant lesions for curative or palliative purposes by using either external or endoscopic irradiation approaches via non-coherent or laser light sources.

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“…Moreover, the antitumour efficacy of PDT could be enhanced through an effective immunoadjuvant to further expand its usefulness for a possible control of distant metastasis and recurrence. However, in clinical practice, the optimal PDT regimen for achieving tumour ablation might be different from the optimal PDT regimen for producing immune response 54 . Immunological approaches used to potentiate PDT in general can be divided into non-specific and specific methods 55 .…”

Section: Therapeutic Implications (Methods For Improving the Therapeumentioning

confidence: 99%

Photodynamic therapy for enhancing antitumour immunity

Pizova

Tománková²,

Daskova³

et al. 2012

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. Photodynamic therapy (PDT) is a new modality in cancer treatment. It is based on the tumour-selective accumulation of a photosensitizer followed by irradiation with light of a specific wavelength. PDT is becoming widely accepted owing to its relative specificity and selectivity along with absence of the harmful side-effects of chemo and radiotherapy. There are three known distinct mechanisms of tumour destruction following PDT, generation of reactive oxygen species which can directly kill tumour cells, tumour vascular shutdown which can independently lead to tumour destruction via lack of oxygen and nutrients and thirdly enhanced antitumour immunity. Methods. A review based on the literature acquired from the PubMed database from 1983 with a focus on the enhanced antitumour immunity effects of PTD. Results and conclusion. Tumour cell death is accompanied by the release of a large number of inflammatory mediators. These induce a non-specific inflammatory response followed by gradual adaptive antitumour immunity. Further, a combination of PDT with the immunological approach has the potential to improve PDT efficiency and increase the cure rate. This short review covers specific methods for achieving these goals.

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Combination of photodynamic therapy and immunomodulation: Current status and future trends

Cited by 55 publications

References 77 publications

The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages

The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages

Basic and Clinical Aspects of Photodynamic Therapy

Photodynamic therapy for enhancing antitumour immunity

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