Photosensitized singlet oxygen generation and detection: Recent advances and future perspectives in cancer photodynamic therapy

Abstract

Photodynamic therapy (PDT) uses photosensitizers and visible light in combination with molecular oxygen to produce reactive oxygen species (ROS) that kill malignant cells by apoptosis and/or necrosis, shut down the tumor microvasculature and stimulate the host immune system. The excited singlet state of oxygen ( 1 O 2 ) is recognized to be the main cytotoxic ROS generated during PDT for the majority of photosensitizers used clinically and for many investigational new agents, so that maximizing its production within tumor cells and tissues can improve the therapeutic response, and several emerging and novel approaches for this are summarized. Quantitative techniques for 1 O 2 production measurement during photosensitization are also of immense importance of value for both preclinical research and future clinical practice. In this review, emerging strategies for enhanced photosensitized 1 O 2 generation are introduced, while recent advances in direct detection and imaging of 1 O 2 luminescence are summarized. In addition, the correlation between cumulative 1 O 2 luminescence and PDT efficiency will be highlighted. Meanwhile, the validation of 1 O 2 luminescence dosimetry for PDT application is also considered. This review concludes with a discussion on future demands of 1 O 2 luminescence detection for PDT dosimetry, with particular emphasis on clinical translation.Eye-catching color image for graphical abstract.

Self‐Amplified Photodynamic Therapy through the 1O2‐Mediated Internalization of Photosensitizers from a Ppa‐Bearing Block Copolymer

“…1,3‐Diphenylisobenzofuran (DPBF) was used as a 1 O 2 indicator . As shown in Figure b, VSP nanoparticles without pretreatment with light irradiation showed no obvious difference in comparison to OCP nanoparticles, but when VSP nanoparticles were pretreated with light irradiation, a rapid decrease in the absorbance of DPBF was observed, meaning more 1 O 2 was generated by irradiation.…”

Biophotonics in China

“…The direct method proposed by them is based on the direct detection of near‐infrared NIR luminescence of 1 O 2 around 1270 nm using NIR photomultiplier tubes (R5509‐43/H10330‐45, Hamamatsu, Japan). In order to predict the effectiveness of light‐based therapies, a novel configuration of a near‐IR‐sensitive InGaAs camera (Xenics Model XEVA‐1.7‐320, Leuven, Belgium) and adaptive optics for fast imaging of singlet oxygen luminescence in vivo was developed by Li et al., and fast imaging of 1 O 2 luminescence in blood vessels in vivo was achieved .…”

“…Besides the above‐mentioned representative work, the research interests of China researchers are quite diverse, covering technique development through to biomedical applications. Consulting the papers published over the last three years in Journal of Biophotonics, the hot topics include photoacoustic microscopy , other technical improvement for imaging , photodynamic therapy , and human studies .…”

Exploring BODIPY Derivatives as Singlet Oxygen Photosensitizers for PDT

“…by the action of cytotoxic ROS, mainly 1 O 2 , locally generated by the combined action of light and a PS. In this context, the PS should be selectively localized in the specific tissue region limiting undesired effects on healthy tissues (4‐7). Therefore, PDT, and mainly cancer PDT, must be highlighted, due to its minimally invasive character, offering important advantages in comparison with traditional treatments.…”

“…On the other hand, best PS candidates for PDT treatments must accomplish some additional criteria: (1) low cytotoxicity in the absence of light (dark toxicity); (2) selective accumulation in the pathological tissue; (3) limited in vivo stability in order to favor its removal after the PDT treatment; (4) high light absorption in the therapeutical window (spectral region of maximum light penetration into tissues; λ abs > 650 nm, ε ≥ 5 × 10 4 m −1 cm −1 ), to maximize the depth of light penetration into the irradiated tissue; (5) solubility in aqueous media; and (6) high ability to penetrate the cell membranes (4‐7).…”