{Reference Type}: Journal Article
{Title}: Constructing Heavy-Atom-Free Photosensitizers for Hypoxic Tumor Phototherapy Based on Donor-Excited Photoinduced Electron-Transfer-Driven Type-I and Type-II Mechanisms.
{Author}: Miao J;Yao G;Huo Y;Wang B;Zhao W;Guo W;
{Journal}: ACS Appl Mater Interfaces
{Volume}: 16
{Issue}: 31
{Year}: 2024 Aug 7
{Factor}: 10.383
{DOI}: 10.1021/acsami.4c02175
{Abstract}: The spin-orbit charge transfer intersystem crossing (SOCT-ISC) photophysical process has shown great potential for constructing heavy-atom-free photosensitizers (PSs) for photodynamic therapy (PDT) of tumors. However, for almost all such PSs reported to date, the SOCT-ISC is driven by the acceptor-excited photoinduced electron transfer (a-PeT). In this work, for the first time the donor-excited photoinduced electron transfer (d-PeT)-driven SOCT-ISC mechanism is utilized to construct the heavy-atom-free PSs for PDT of tumors by directly installing the electron-deficient N-alkylquinolinium unit (as an electron acceptor) into the meso-position of the near-infrared (NIR) distyryl Bodipy chromophore (as an electron donor). In the less polar environment, the PSs exist as the monomer and promote the production of singlet oxygen (1O2) (Type-II) relying on the d-PeT-driven population of the triplet excited state via SOCT-ISC, whereas in the aqueous environment, they exist as nanoaggregates and induce the generation of superoxides (O2-•) and hydroxyl radicals (HO•) (Type-I) via the d-PeT-driven formation of the delocalized charge-separated state. The PSs could rapidly be internalized into cancer cells and induce the simultaneous production of intracellular 1O2, O2-•, and HO• upon NIR light irradiation, endowing the PSs with superb photocytotoxicity with IC50 values up to submicromolar levels whether under normoxia or under hypoxia. Based on the PSs platform, a tumor-targetable PS is developed, and its abilities in killing cancer cells and in ablating tumors without damage to normal cells/tissues under NIR light irradiation are verified in vitro and in vivo. The study expands the design scope of PSs by introducing the d-PeT conception, thus being highly valuable for achieving novel PSs in the realm of tumor PDT.