Thionated organic compounds as emerging heavy-atom-free photodynamic therapy agents.

Luis A Ortiz-Rodríguez,Carlos E Crespo-Hernández

doi:10.1039/d0sc04747c

Luis A Ortiz-Rodríguez, Carlos E Crespo-Hernández

Open Access

https://doi.org/10.1039/d0sc04747c

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Abstract

This minireview focuses on recent progress in developing heavy-atom-free photosensitizers based on the thionation of nucleic acid derivatives and other biocompatible organic compounds for prospective applications in photodynamic therapy. Particular attention is given to the use of thionated nucleobase derivatives as “one-two punch” photodynamic agents. These versatile photosensitizers can act as “Trojan horses” upon metabolization into DNA and exposure to activating light. Their incorporation into cellular DNA increases their selectivity and photodynamic efficacy against highly proliferating skin cancer tumor cells, while simultaneously enabling the use of low irradiation doses both in the presence and in the absence of molecular oxygen. Also reviewed are their primary photochemical reactions, modes of action, and photosensitization mechanisms. New developments of emerging thionated organic photosensitizers absorbing visible and near-infrared radiation are highlighted. Future research directions, as well as, other prospective applications of heavy-atom-free, thionated photosensitizers are discussed.

Highlights

In the USA, it is estimated that more than 3 million Americans are affected with non-melanoma skin cancers (NMSC) annually, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).[4,5]
BCC increased by 145%, while it increased by 263% for SCC over the same period.[6]
actinic keratosis (AK) can develop into keratinocyte carcinoma (KC), including BCC and SCC of the skin, which are the most common cancers in the USA and in

Summary

Introduction

BCC increased by 145%, while it increased by 263% for SCC over the same period.[6]. Likewise, actinic keratosis (AK) is a common precancerous skin condition caused by DNA damage in the keratinocytes of the epidermis due to chronic exposure to sunlight. Bern Kohler's group at The Ohio State University, he joined CWRU (2007), where he received a Frank Hovorka Assistant Professorship in Chemistry (2012–2014) He was promoted to Associate Professor in 2014 and to Professor in 2019. Topical PDT offers a superior cosmetic outcome than conventional therapies such as surgery, radiation therapy, and chemotherapy, which can cause serious side effects by the loss of normal cell function due to nonspeci c targeting of the treatments.[1,21] PDT is approved for the treatment of wide-ranging NMSC in Europe, USA, and in other countries,[21,22,23] and has demonstrated high efficacy for AK, super cial and nodular BCC, squamous cell carcinoma in situ or Bowen's disease, and eld cancerization.[22] It has been recommended for use in photo-rejuvenation, acne treatment, and other skin conditions.[23]. To minimize the side effects, the photosensitizer should have excellent biocompatibility and photostability with no dark toxicity, large absorption coefficients in the optical window to be used for PDT, and should exhibit appropriate retention time in living tissues with relatively rapid clearance from the body.[36,37] In addition, the photosensitizer should be widely available with a high degree of chemical purity and good stability to allow for prolonged storage, and should be inexpensive and simple to synthetized.[36]

Photochemical mechanisms and PDT-mediated cytotoxicity

Photosensitization mechanism of thiobases

Findings

Conclusions