Measurement of Cyanine Dye Photobleaching in Photosensitizer Cyanine Dye Conjugates Could Help in Optimizing Light Dosimetry for Improved Photodynamic Therapy of Cancer.

Ravindra Pandey,Ravindra Cheruku,Nadine James,Ulas Sunar,Joseph Missert

doi:10.3390/molecules23081842

Ravindra Pandey, Ravindra Cheruku + Show 3 more

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https://doi.org/10.3390/molecules23081842

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Abstract

Photodynamic therapy (PDT) of cancer is dependent on three primary components: photosensitizer (PS), light and oxygen. Because these components are interdependent and vary during the dynamic process of PDT, assessing PDT efficacy may not be trivial. Therefore, it has become necessary to develop pre-treatment planning, on-line monitoring and dosimetry strategies during PDT, which become more critical for two or more chromophore systems, for example, PS-CD (Photosensitizer-Cyanine dye) conjugates developed in our laboratory for fluorescence-imaging and PDT of cancer. In this study, we observed a significant impact of variable light dosimetry; (i) high light fluence and fluence rate (light dose: 135 J/cm2, fluence rate: 75 mW/cm2) and (ii) low light fluence and fluence rate (128 J/cm2 and 14 mW/cm2 and 128 J/cm2 and 7 mW/cm2) in photobleaching of the individual chromophores of PS-CD conjugates and their long-term tumor response. The fluorescence at the near-infrared (NIR) region of the PS-NIR fluorophore conjugate was assessed intermittently via fluorescence imaging. The loss of fluorescence, photobleaching, caused by singlet oxygen from the PS was mapped continuously during PDT. The tumor responses (BALB/c mice bearing Colon26 tumors) were assessed after PDT by measuring tumor sizes daily. Our results showed distinctive photobleaching kinetics rates between the PS and CD. Interestingly, compared to higher light fluence, the tumors exposed at low light fluence showed reduced photobleaching and enhanced long-term PDT efficacy. The presence of NIR fluorophore in PS-CD conjugates provides an opportunity of fluorescence imaging and monitoring the photobleaching rate of the CD moiety for large and deeply seated tumors and assessing PDT tumor response in real-time.

Highlights

Photodynamic therapy (PDT) was initially developed for the local destruction of solid tumors [1,2] and is currently being used worldwide in the treatment of several tumors including skin basal cell carcinoma (BCC) [3], lung [4,5,6], esophagus [7,8,9,10,11], bladder, head and neck [4,6,12], brain [13,14,15,16,17], ocular melanoma, ovarian, prostate [8,9,10,11,12,13,14,15,16,17,18,19,20], renal cell, cervix, pancreas and bone [21]
We aim to investigate the utility of the photosensitizer-near infrared fluorophores conjugate (PS-NIRF) as fluorescence probes and markers for PDT light dosimetry
Fluorophore CD of the conjugates photobleached at a much faster rate than HPPH and the rate of bleaching was in the order of 9 > 10 > 8 > 11, which correlated well with their in vivo PDT responses when irradiated at 128 J/cm2 and 14 mW/cm2, using a drug dose of 1.5 μmol/kg

Summary

Introduction

PDT was initially developed for the local destruction of solid tumors [1,2] and is currently being used worldwide in the treatment of several tumors including skin basal cell carcinoma (BCC) [3], lung [4,5,6], esophagus [7,8,9,10,11], bladder, head and neck [4,6,12], brain [13,14,15,16,17], ocular melanoma, ovarian, prostate [8,9,10,11,12,13,14,15,16,17,18,19,20], renal cell, cervix, pancreas and bone [21]. Molecules 2018, 23, 1842 for many diseases, it is still not being practiced in mainstream oncology In part, this is because the therapy using the light dosimetry based on measured or calculated physical values is not yet optimized. A better understanding of PDT dosimetry is important so it will be a reliable tool for controlled enhancement of the therapeutic outcome

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