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 (NI-Por and NI-ZnPor) 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 NI-Por NPs and NI-ZnPor NPs 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 NI-Por NPs and NI-ZnPor NPs was confirmed using DCFH-DA as an indicator. Furthermore, the localization of NI-Por NP and NI-ZnPor NP 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 IC 50 of NI-Por NPs and NI-ZnPor NPs 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.

Assembled small organic molecules for photodynamic therapy and photothermal therapy

“…Both NI-Por and its Zinc complex (NI-ZnPor) can self-assemble in nanoparticles for performing PDT/PTT synergistic cancer therapy under light irradiation. 82 Yang et al synthesized zinc phthalocyanine molecules containing alkyl chain and hydroxyl groups (ZnPc). The selfassembly of ZnPc can form nanoparticles with uorescence (Fig.…”

Nanoparticles for Triple Drug Release for Combined Chemo‐ and Photodynamic Therapy

“…This combination effect was assessed in detail for HeLa cells. For this cell line, the calculated IC 50 value for MSN 1 was 8.36 μg mL À 1 and is equivalent to the release of 0.19 μg•mL À 1 of free DOX and 0.002 μg mL À 1 of CPT from the conjugate Pc-CPT (5). These values were calculated as the release of drugs at pH 5.5, which is the average pH found in late endosomes and lysosomes of HeLa cells.…”

“…[2a,j,3] In recent years, a variety of multifunctional DDSs for dual release of drugs have been proposed. Furthermore, to improve the efficiency of such treatments, specially engineered DDSs have envisioned combining not only drugs [4] but also different therapies such as thermal therapy [5] or photodynamic therapy (PDT). [6] However, to attain such level of complexity the preparation of these devices entails the use of many components (polymers, linkers, smart gates, etc.)…”

Nanoplatform Self-assembly From Small Molecules of Porphyrin Derivatives for NIR-II Fluorescence Imaging Guided Photothermal-immunotherapy

“…Under these circumstances, a single porphyrin-derived uorophore simultaneously bearing NIR uorescence and photothermal conversion capacity needs to rational molecular design to balance radiative and nonradiative pathways of excited state. Our groups and others have developed various amphiphilic porphyrins with simple molecular structure which can self-assembly into nanoparticles for PTT treatment [28,29,[31][32][33][34], but most of them have no uorescence emission due to the aggregation caused quenching (ACQ) effect and the narrowed optical gap, not to mention bearing NIR-II emission.…”