Self-Assembled Naphthalimide Conjugated Porphyrin Nanomaterials with D–A Structure for PDT/PTT Synergistic Therapy

Abstract

Light-activated phototherapy, including photothermal and photodynamic therapy, has become a new way for spatiotemporal control and noninvasive treatment of cancer. In this study, two new organic porphyrin molecules (<b>NI-Por</b> and <b>NI-ZnPor</b>) with donor (D)-acceptor (A) structure were designed and synthesized. The donor-acceptor pairs facilitated the intermolecular electron transfer, resulting in the enhancement of near-infrared (NIR) absorbance and nonradiative heat generation. After self-assembling, the nanoparticles were formed with the size around 60 nm. Relative to that of organic molecules, the absorption of <b>NI-Por NPs</b> and <b>NI-ZnPor NPs</b> broadened and red-shifted to the near-infrared region. Moreover, the porphyrin-containing nanoparticles can generate heat and reactive oxygen species (ROS) simultaneously induced by a single laser (635 nm). The intracellular reactive oxygen species production of <b>NI-Por NPs</b> and <b>NI-ZnPor NPs</b> was confirmed using DCFH-DA as an indicator. Furthermore, the localization of <b>NI-Por NP</b> and <b>NI-ZnPor NP</b> in HeLa cells was verified by fluorescence confocal laser microscopy. The photocytoxicity of two nanoparticles against HeLa cells was evaluated through the CCK-8 method. The IC₅₀ of <b>NI-Por NPs</b> and <b>NI-ZnPor NPs</b> upon 635 nm laser irradiation was calculated to be 6.92 μg/mL and 5.86 μg/mL, respectively. Furthermore, the PDT/PTT synergistic effect of NPs under a 635 nm laser was verified through different treatment groups in vitro. All these results demonstrated that the as-prepared porphyrin-based nanoparticles are promising nanoagents for PDT/PTT in clinic.