Endoperoxides Compounds for Highly Efficient Cancer Treatment under Hypoxia

Abstract

Photodynamic therapy (PDT) for cancer treatment has garnered tremendous attention with its promising non‐invasiveness, low side effects, and spatiotemporal selectivity. However, the hypoxic microenvironment in solid tumours remains a serious resistant factor to reducing the effects of PDT. Endoperoxides are successfully utilized as the chemical storage or supplier of singlet oxygen (1O2), the active substance for PDT in materials and other domains. Recent reports indicated that this type of compound could remarkably enhance the therapeutic effects of PDT under hypoxia. This concept mainly introduces a few representative endoperoxides and the outlook of their potent application for treating hypoxic cancer cells.

Biological Action of Singlet Molecular Oxygen from the Standpoint of Cell Signaling, Injury and Death

“…Endoperoxides that release 1 O 2 without other ROS have been developed to evaluate its unique reaction [ 13 , 50 ]. Naphthalene endoperoxide-based 1 O 2 donor compounds were first developed, and the structure–function relationships of the compounds have been described in detail in a review article [ 13 ].…”

“…For the efficient delivery of a 1 O 2 donor to cancer cells, a porphyrin-based covalent organic framework that contains a naphthalene endoperoxide has also been developed [ 54 ]. Trials to develop new types of endoperoxides, which are based on 2-pyridone and anthracene, are also underway [ 50 ]. Two 1 O 2 -producing systems, photodynamic reactions and naphthalene endoperoxides, have provided rather consistent results so far [ 13 ], implying that the contribution of other byproducts may be negligible.…”

Recent progress in metal complexes functionalized nanomaterials for photodynamic therapy

“…[52][53][54][55] Besides regulation of the oxygen concentration at the tumour site, research efforts have also been devoted to the development of PSs which act by an oxygen-independent mechanism, also referred to as the remote-controlled release of 1 O 2 . Aromatic compounds including naphthalene, anthracene, etc., which capture and store singlet oxygen to generate endoperoxides (EPOs), 56 have been widely investigated and employed in material science 57 and chemical synthesis. 58 After light irradiation or thermal reduction, the physical quenching pathway through intersystem crossing enables the exciplexes to transform into excited triplet complexes, ultimately generating reactive radical products before decomposition into starting materials.…”

“…Aromatic compounds including naphthalene, anthracene, etc. , which capture and store singlet oxygen to generate endoperoxides (EPOs), 56 have been widely investigated and employed in material science 57 and chemical synthesis. 58 After light irradiation or thermal reduction, the physical quenching pathway through intersystem crossing enables the exciplexes to transform into excited triplet complexes, ultimately generating reactive radical products before decomposition into starting materials.…”

Synthesis and Evaluation of Novel meso-Tetraphenyltetrabenzoporphyrins for Photodynamic Therapy

“…Photodynamic therapy (PDT) is a minimally invasive therapeutic method which has been approved for the treatment of several cancer types such as lung cancer, breast cancer, prostate cancer, and bladder cancer. − PDT involves three basic elements: photosensitizer (PS), light, and oxygen. The combination of these three elements results in the generation of reactive oxygen species (ROS) like hydroxyl radical (·OH) and singlet oxygen ( 1 O 2 ) which can interact with biological molecules to inhibit the growth of tumor cells and/or destroy tumor tissues through apoptosis or necrosis. − …”