BODIPY-Based Photothermal Agents with Excellent Phototoxic Indices for Cancer Treatment

Abstract

Here, we report six novel, easily accessible BODIPY-based agents for cancer treatment. In contrast to established photodynamic therapy (PDT) agents, these BODIPY-based compounds show additional photothermal activity and their cytotoxicity is not dependent on the generation of reactive oxygen species (ROS). The agents show high photocytotoxicity upon irradiation with light and low dark toxicity in different cancer cell lines in 2D culture as well as in 3D multicellular tumor spheroids (MCTSs). The ratio of dark to light toxicity (phototoxic index, PI) of these agents reaches striking values exceeding 830,000 after irradiation with energetically low doses of light at 630 nm. The oxygen-dependent mechanism of action (MOA) of established photosensitizers (PSs) hampers effective clinical deployment of these agents. Under hypoxic conditions (0.2% O2), which are known to limit the efficiency of conventional PSs in solid tumors, photocytotoxicity was induced at the same concentration levels, indicating an oxygen-independent photothermal MOA. With a PI exceeding 360,000 under hypoxic conditions, both PI values are the highest reported to date. We anticipate that small molecule agents with a photothermal MOA, such as the BODIPY-based compounds reported in this work, may overcome this barrier and provide a new avenue to cancer therapy.

Ru(II) Phenanthroline-Based Oligothienyl Complexes as Phototherapy Agents

“…In addition, PDT can induce hypoxia as oxygen is consumed during irradiation. , Decreased generation of ROS limits damage to cancerous cells. To address this, there is motivation to develop light-triggered compounds that exploit oxygen-independent mechanisms for phototoxicity. − In this context, metal complexes such as Ru(II) polypyridyl systems have attracted considerable attention. ,,,− Judicious choice of ligand–metal combinations provides access to a variety of excited-state configurations with characteristic photophysical properties and reactivities. Strategies have included photorelease of bulky ligands to reveal phototoxic metals and/or ligands, ,,,,,− photocaging of chemotherapeutics and enzyme inhibitors, ,,,,,− …”

Comparing PVP and Polymeric Micellar Formulations of a PEGylated Photosensitizing Phthalocyanine by NMR and Optical Techniques

“…The singlet oxygen quantum yields (Φ Δ ) of Pc1-PBS , Pc1-P188 , Pc1-P84 , Pc1-F127 , Pc1-RH40 , and Pc1-PVP were determined with the aid of a previously reported setup. , The samples were prepared in D 2 O-based PBS, and the solutions were placed in a 10 × 4 mm 114F-10-40 fluorescence 1 mL quartz glass cuvette (Hellma Analytics, Germany). The cuvette was oriented in a way that the light path equals to 10 mm.…”

An AIE-active type I photosensitizer based on N,N′-diphenyl-dihydrophenazine for high-performance photodynamic therapy under hypoxia

“…[1][2][3][4] It relies on the utilization of photosensitizers (PSs) to convert endogenous molecular oxygen into cytotoxic reactive oxygen species (ROS) upon light exposure. [5][6][7][8][9] Under illumination, the PSs can be transformed from the singlet ground state (S 0 ) to the excited singlet state (S 1 ) and reaches the triplet state (T 1 ) through intersystem crossing (ISC). 10 Subsequently, the T 1 state triggers different photochemical reactions, which eventually lead to two types of PDT: type I and type II (Fig.…”