Photodynamic therapy (PDT) with an oxygen-dependent character is a noninvasive therapeutic method for cancer treatment. However, its clinical therapeutic effect is greatly restricted by tumor hypoxia. What's more, both PDT-mediated oxygen consumption and microvascular damage aggravate tumor hypoxia, thus, further impeding therapeutic outcomes. Compared to type II PDT with high oxygen dependence and high oxygen consumption, type I PDT with less oxygen consumption exhibits great potential to overcome the vicious hypoxic plight in solid tumors. Type I photosensitizers (PSs) are significantly important for determining the therapeutic efficacy of PDT, which performs an electron transfer photochemical reaction with the surrounding oxygen/substrates to generate highly cytotoxic free radicals such as superoxide radicals (˙O₂ ⁻) as type I ROS. In particular, the primary precursor (˙O₂ ⁻) would progressively undergo a superoxide dismutase (SOD)-mediated disproportionation reaction and a Haber–Weiss/Fenton reaction, yielding higher cytotoxic species (˙OH) with better anticancer effects. As a result, developing high-performance type I PSs to treat hypoxic tumors has become more and more important and urgent. Herein, the latest progress of organic type I PSs (such as AIE-active cationic/neutral PSs, cationic/neutral PSs, polymer-based PSs and supramolecular self-assembled PSs) for monotherapy or synergistic therapeutic modalities is summarized. The molecular design principles and strategies (donor–acceptor system, anion–π⁺ incorporation, polymerization and cationization) are highlighted. Furthermore, the future challenges and prospects of type I PSs in hypoxia-overcoming PDT are proposed.

Aggregation-induced emission luminogens (AIEgens) exhibit efficient cytotoxic reactive oxygen species (ROS) generation capability and unique light-up features in the aggregated state, which have been well explored in image-guided photodynamic therapy (PDT). However, the limited penetration depth of light in tissue severely hinders AIEgens as a candidate for primary or adjunctive therapy for clinical applications. Coincidentally, microwaves (MWs) show a distinct advantage for deeper penetration depth in tissues than light. Herein, for the first time, we report AIEgen-mediated microwave dynamic therapy (MWDT) for cancer treatment. We found that two AIEgens (TPEPy-I and TPEPy-PF6) served as a new type of microwave (MW) sensitizers to produce ROS, including singlet oxygen (¹O₂), resulting in efficient destructions of cancer cells. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and live/dead assays reveal that the two AIEgens when activated by MW irradiation can effectively kill cancer cells with average IC-50 values of 2.73 and 3.22 μM, respectively. Overall, the ability of the two AIEgens to be activated by MW not only overcomes the limitations of conventional PDT, but also helps to improve existing MW ablation therapy by reducing the MW dose required to achieve the same therapeutic outcome, thus reducing the occurrence of side-effects of MW radiation.