Fig. 1. Mechanisms of Type I and Type II photodynamic therapy

Fig. 2. Compounds belong to the phenothiazine derivatives. (a) Schematic representation of the photoinduced free radical generation mechanism of ENBS-B^[23]; (b) schematic illustration of deep tumor eradication under FRET mechanism using Type I photosensitizer ENBOS^[24]; (c) photodynamic O₂-economizer of SORgenTAM and its action mechanisms of multipronged reversal of hypoxia-driven PDT resistance^[25]; (d) chemical structure of NBS-ER and illustration of cell death mechanism photoinduced by NBS-ER^[27]

Fig. 3. Compounds belong to BODIPY derivatives. (a) Type I photosensitizers based on BODIPY structure; (b) illustrations of structure of α,β-linked BODIPY and photo-induced exclusive generation of O₂^-•[38]; (c) efficient relaxation pathway from excited state S₁ to triplet state T₁ for α, β-connected BODIPY and comparison of energy difference between T₁ and ground state S₀ with the energy required for sensitizing ³O₂ to ¹O₂^[38]

Fig. 4. Supramolecular photosensitizers with Type I ROS generation ability. (a) A concise description of Type I/II mechanisms and a comparison of various Type I photosensitizer design strategies^[39]; (b) fabrication of supramolecular photosensitizers HG and photo-induced generation of ROS^[39]; (c) schematic illustrations of the preparation of DA, as well as photoinduced generation of ·OH and reduction of pyruvic acid^[40]; (d) schematic illustration of the generation mechanism of ·OH with or without oxygen^[40]; (e) schematic representations of the preparation method for PPIAB NPs and the mechanism of O₂^-• generation under hypoxic conditions^[41]; (f) schematic diagrams illustrating the preparation method of PBV NPs, elucidating the generation mechanism of O₂^-• and highlighting the tumor therapy potential through PBV NPs vascular occlusion and Type I photodynamic synergy^[42]

Fig. 5. Naphthalene amide derivative^[44]. (a) Schematic diagram depicts the mechanism underlying the formation of triplet states; (b) schematic illustration of the assembly and partial disassembly processes of MANI-S; (c) relative changes in fluorescence intensity of ROS detected by DCFH-DA; (d) relative changes in fluorescence intensity of O₂^-• detected by DHE

Fig. 6. Fluorescein derivatives. (a) Fluorescein derivatives with the capability of generating Type I ROS; (b) a simplified schematic diagram illustrating the photosensitizer (PS) as an “electron pump” and BSA as an “electron reservoir”, accompanied by a concise description of the Type I photosensitive process^[49]; (c) chemical structures of fluorescein derivatives Fl-C2 and Fl-C18 and their photosensitive mechanisms under various conditions^[50]; (d) assembly diagram of supramolecular photosensitizer (Rh19-MA-C18) and concise elucidation of Type I photosensitization mechanism^[51]

Fig. 7. Porphyrin type photosensitizers. (a) Diverse photosensitizers derived from the porphyrin structure; (b) schematic diagram of cationic porphyrin photosensitizer P1 employed in photodynamic therapy of tumors under hypoxic condition^[59]; (c) schematic diagram illustrating the assembly process of Ergo-Ce6 NPs photosensitizer and its application in anti-tumor therapy^[62]

Fig. 8. Type I AIE photosensitizers

Fig. 9. Design of Type I AIE organic photosensitizers based on D-A configuration. (a) Photophysical and photochemical mechanisms of Type I photosensitizers α-TPA-PIO and β-TPA-PIO, based on the PIO core , as well as cytological processes involved in PDT treatment^[70]; (b) schematic representation of the molecular design of TTFMN and its nanoparticle application for fluorescence-guided photodynamic therapy against tumors^[76]; (c) schematic diagram illustration of AQPO NPs for hypoxia-overcoming cancer treatment in vivo and in vitro^[77]; (d) schematic representation of the molecular structure of PPR-2CN and its nanoparticles employed for multimodal tumor therapy and diagnosis^[78]

Fig. 10. AIE-based photosensitizers for the combination therapy of PDT and PTT with a D-A configuration. (a) Schematic diagram illustrating the application of photosensitizer NS-STPA in fluorescence imaging-guided multimodal phototherapy and its corresponding mechanism^[84]; (b) schematic representation of PQ derivatives and their corresponding nanoparticles for Type I PDT and PTT combination therapy^[85]; (c) schematic illustration of DTTVBI NPs as a tumor reversibly pH-switchable theranostic platform for precise PTT and Type I PDT^[87]

Fig. 11. Cationic approach for the synthesis of Type I AIE photosensitizers. (a) Schematic diagram illustrating the cationic molecular engineering strategy for enhancing PDT performance^[88]; (b) molecular cationic approach to enhance Type I ROS production in photodynamic antibacterial experiments^[89]; (c) distributions analysis of HOMO and LUMO, determination of ΔE_ST and K_ISC values for four AIE photosensitizers^[89]; (d) molecular cationic and cyano-introduced strategies for enhancing Type I and Type II ROS production in photodynamic antibacterial applications^[90]

Fig. 12. Type I NIR-II photosensitizers. (a) Schematic diagram of a hypoxia-resistant NIR-II luminescent photosensitizer (COi6-4Cl) for tumor therapy^[98]; (b) illustration of A-D-A type π-conjugated small molecules photosensitizers BMIC-BO-4Cl and BMIC-BO-4F^[99]; (c) schematic illustration of the preparation of Type I NIR-II photosensitizers PTS, PTSe, and PTTe NPs, and schematic diagram of PDT/PTT action under the hypoxic condition^[100]

Fig. 13. Alternative organic photosensitizers of Type I