Photodynamic therapy (PDT) is a promising method for the treatment of cancer, because of its advantages including a low toxicity, non-drug-resistant character, and targeting capability. From a photochemical aspect, a critical property of triplet photosensitizers (PSs) used for PDT reagents is the intersystem crossing (ISC) efficiency. Conventional PDT reagents are limited to porphyrin compounds. However, these compounds are difficult to prepare, purify, and derivatize. Thus, new molecular structure paradigms are desired to develop novel, efficient, and versatile PDT reagents, especially those contain no heavy atoms, such as Pt or I, etc. Unfortunately, the ISC ability of heavy atom-free organic compounds is usually elusive, and it is difficult to predict the ISC capability of these compounds and design novel heavy atom-free PDT reagents. Herein, from a photophysical perspective, we summarize the recent developments of heavy atom-free triplet PSs, including methods based on radical-enhanced ISC (REISC, facilitated by electron spin–spin interaction), twisted π-conjugation system-induced ISC, the use of fullerene C₆₀ as an electron spin converter in antenna-C₆₀ dyads, energetically matched S₁/T_n states-enhanced ISC, etc. The application of these compounds in PDT is also briefly introduced. Most of the presented examples are the works of our research group.

Long-lived charge separated (CS) triplet state (2.6 μs) and thermally activated delayed fluorescence (TADF) [τ = 282 ns (90.4%)/2.4 μs (9.6%)] were observed in an anthraquinone-phenoxazine electron donor–acceptor dyad via the electron spin control method, and emissive ¹CS and non-emissive ³CS states were discriminated via nanosecond transient absorption spectroscopy and global analysis.