Journal of Innovative Optical Health Sciences

Photodynamic therapy (PDT) has already been a multifunctional modality for various tumors and nontumorous diseases. However, the development of photosensitizers is relatively delayed, compared with the tremendous progress in laser technology. Elsinochrome A (EA), a perylenequinonoid pigment from China, has all the typical advantages of perylenequinones. Moreover, singlet oxygen quantum yield of EA is superior to other kinds of photosensitizers and EA could be artificially biosynthesized at present, which make it an alternative candidate for PDT. In this review, the photophysics, photochemistry, photobiology and chemical or biological syntheses of EA photosensitizers are briefly presented. Besides, the future prospects of EA photosensitizers are also proposed.

Photodynamic therapy (PDT) of cancer is a two-step drug-device combination modality, which involves the topical or systemic administration of a photosensitizer followed by light illumination of cancer site. In the presence of oxygen molecules, the light illumination of photosensitizer (PS) can lead to the generation of cytotoxic reactive oxygen species (ROS) and consequently destroy cancer. Similar to many other anticancer therapies, PDT is also subject to intrinsic cancer resistance mediated by multidrug resistance (MDR) mechanisms. This paper will review the recent progress in understanding the interaction between MDR transporters and PS uptake. The strategies that can be used in a clinical setting to overcome or bypass MDR will also be discussed.

Photodynamic therapy (PDT) has been a routine treatment of tumors and some microvascular diseases, but clinically available photosensitizers are still scarce. Among all kinds of photosensitizers, hypocrellins possess the most characteristics of ideal photosensitizers, such as, high photo-activity but low dark toxicity, fast clearance from tissues. This review is focused on two main topics, drug-delivery problem of hypocrellins and how the environment-sensitive fluorescence of hypocrellins was used for recognition of various biomolecules. Drug-delivery of hypocrellins was mainly achieved in two strategies — preparing the drug-delivery vehicles and finding quantitatively amphiphilic derivatives. Hypocrellin fluorescence originated from the intramolecular proton transfer is very distinct from other kinds of photosensitizers. Recently, it was proved that quantitative hypocrellin fluorescence could not only recognize various biomolecules, including proteins, polysaccharides and lipids, but also distinguish the specific binding from nonspecific binding with some kind of biomolecules. Meantime, hypocrellin fluorescence was pH-sensitive. It is known that tumor cells or tissues have the features of a large amount of lipid, neonatal collagen, over-expression of polysaccharides, and lower pH values compared to normal tissues. According to the relative but not absolute specificity, further studies on quantitative recognition of various biomolecules at a cellular level, may find a new clue to treat tumors by joint usage of photodynamic diagnosis (PDD) and PDT.

Invasive grade III and IV malignant gliomas remain difficult to treat with a typical survival time post-diagnosis hovering around 16 months with only minor extension thereof seen in the past decade, whereas some improvements have been obtained towards five-year survival rates for which completeness of resection is a prerequisite. Optical techniques such as fluorescence guided resection (FGR) and photodynamic therapy (PDT) are promising adjuvant techniques to increase the tumor volume reduction fraction. PDT has been used in combination with surgical resection or alternatively as standalone treatment strategy with some success in extending the median survival time of patients compared to surgery alone and the current standard of care. This document reviews the outcome of past clinical trials and highlights the general shift in PDT therapeutic approaches. It also looks at the current approaches for interstitial PDT and research options into increasing PDT's glioma treatment efficacy through exploiting both physical and biological-based approaches to maximize PDT selectivity and therapeutic index, particularly in brain adjacent to tumor (BAT). Potential reasons for failing to demonstrate a significant survival advantage in prior PDT clinical trials will become evident in light of the improved understanding of glioma biology and PDT dosimetry.

Photodynamic therapy (PDT) represents a promising method for treatment of cancerous tumors. The chemical and physical properties of used photosensitizer (PS) play key roles in the treatment efficacy. In this study, a novel PS, 5,10,15,20-tetrakis((5-dipropylamino)pentyl)-chlorin (TDPC) which displayed a characteristic long wavelength absorption peak at 650 nm were synthesized. It also shows a singlet oxygen generation rate of 4.257 min^-1. Generally, TDPC is localized in mitochondria and nucleus of cell. After light irradiation with 650 nm laser, it can kill many types of cell, in addition, TDPC–PDT can destroy ECA-109 tumor in nude mice and a necrotic scab was formed eventually. The expression levels of many genes which regulated cell growth and apoptosis were determined by RT-PCR following TDPC–PDT. The results showed that it either increased or decreased, among which, the expression level of TNFSF13, a member of tumor necrosis factor superfamily, increased significantly. In general, TDPC is an effective antitumor PS in vitro and in vivo and is worthy of further study as a new drug candidate. TNFSF13 will be an important molecular target for the discovery of new PSs.

Low-level laser therapy (LLLT) has been clinically utilized for many indications in medicine requiring protection from cell/tissue death, stimulation of healing and repair of injuries, pain reduction, swelling and inflammation. Presently, the use of LLLT to treat stroke, traumatic brain injury and cognitive dysfunction are attracting growing interest. Near-infrared light is capable of penetrating into the cerebral cortex, allowing noninvasive treatments to be carried out with few treatment-related adverse events. Optimization of LLLT treatment effect is a crucial issue of this field; however, only a few experimental tests on mice for wavelength selection have been reported. We addressed this issue by low-cost, straightforward and quantitative comparisons on light dosage distribution within visible Chinese human head by Monte Carlo modeling of near-infrared light propagation. Optimized selection in wavelength, beam type and size were given based on comparisons among frequently used setups (i.e., wavelengths: 660, 810 and 980 nm; beam type: Gaussian and flat beam; beam diameter: 2, 4 and 6 cm). This study provided an efficient way for guiding the optimization of LLLT setup and selection on wavelength, beam type and size for clinical brain LLLT.

In this study, a novel photosensitizer meso-tetra (3-pyrrolidinomethyl-4-methoxyphenyl) chlorin (TPMC) was reported. It displays a characteristic long wavelength absorption peak at 656 nm and it shows a singlet oxygen quantum yield of 0.48. After light irradiation with 650 nm laser, it can kill Eca-109 and SMMC-7721 cells in vitro (25 mW/cm², 1.2 to 3.6 J/cm²) and destroy Eca-109 tumor in nude mice (50 mW/cm², 90 J/cm²). It has the perspective to be developed as a new anti-tumor drug in photodynamic therapy (PDT) photodiagnosis, and deserves further investigation.

Purpose: To evaluate the effectiveness of topical 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) for the treatment of cutaneous lichen planus (LP). Methods: A total of 17 symptomatic LP lesions in 7 Chinese patients were assessed. ALA cream (10%) was applied topically to LP lesions for 3 h. The lesions were irradiated with a 635 nm diode laser at the dose level of 100 J/cm². The treatment was repeated at two-week intervals. Clinical assessment was conducted before each treatment. Follow-up was performed once a month for up to six months. Results: Lesions showed significant improvement after one to four courses of treatments. Complete response was achieved in 13 lesions (five patients) and partial remission in four lesions (two patients). The complete response rate was 71%. There was no significant side effects except the feeling of pain that most patients could tolerate. Follow-up of five patients who achieved complete response showed no signs of recurrence. Conclusion: Topical ALA PDT is effective in the treatment of cutaneous LP.

Premalignant lesions like oral lichen planus (OLP), oral leukoplakia (OL) has a fair probability of transforming into malignancy and they are perverse toward conventional therapies. Photodynamic therapy (PDT) has been considered as an alternative/complimentary therapeutic modality for the management of premalignant lesions. In this study, methylene blue-mediated photodynamic therapy (MB-PDT) was used as a possible alternative method for the treatment of OLP and OL. A total of 15 OLP lesions and 13 OL lesions were enrolled in the study. The patients were irradiated using metal halide lamp filtered at 630 ± 10 nm, with a light exposure dose of 120 J/cm² per sitting. For the OLP lesions, MB-PDT was performed once a week for four weeks and for the OL lesions, MB-PDT was performed twice a week for three weeks. Lesions were evaluated pre- and post- and at follow-up sessions by changes in sign and symptom scores, and size of lesions. We have observed a 53.3% of complete reduction in the treated OLP lesions and their decrease in size, sign and symptom score after treatment and at follow-up session was statistically significant. We have also observed complete response for one OL lesion of the 13 treated lesions. The result indicates that MB-PDT is an effective modality in management of OLP and OL. Among the two types of premalignancies treated with MB-PDT, OLP lesions responded much better than that of OL.

Excited-state singlet oxygen (¹O₂), generated during photodynamic therapy (PDT), is believed to be the primary cytotoxic agent with a number of clinically approved photosensitizers. Its relative concentration in cells or tissues can be measured directly through its near-infrared (NIR) luminescence emission, which has correlated well with in vitro cell and in vivo normal skin treatment responses. Here, its correlation with the response of tumor tissue in vivo is examined, using the photosensitizer meso-tetrahydroxyphenylchlorin (mTHPC) in an animal model comprising luciferase- and green fluorescent protein (GFP)-transduced gliosarcoma grown in a dorsal window chamber. The change in the bioluminescence signal, imaged pretreatment and at 2, 5 and 9 d post treatment, was used as a quantitative measure of the tumor response, which was classified in individual tumors as "non", "moderate" and "strong" in order to reduce the variance in the data. Plotting the bioluminescence-based response vs the ¹O₂ counts demonstrated clear correlation, indicating that ¹O₂ luminescence provides a valid dosimetric technique for PDT in tumor tissue.