A J-aggregated nanoporphyrin overcoming phototoxic side effects in superior phototherapy with two-pronged effects.
Mengyao YangXingshu LiGyoungmi KimRui WangSeong-Jin HongChang-Hee LeeJuyoung YoonPublished in: Chemical science (2022)
Phototherapy has been a promising therapeutic modality for pathological tissue due to its spatiotemporal selectivity and non-invasive characteristics. However, as a core component of phototherapy, a single photosensitizer (PS) nanoplatform integrating excellent therapeutic efficiency and minimal side effects remains an urgent but unmet need. Here, we construct a J-aggregated nano-porphyrin termed MTE based on the self-assembly of methyl-pheophorbide a derivative MPa-TEG (MT) and natural polyphenolic compound epigallocatechin gallate (EGCG). Due to the synergistic interaction between similar large π-conjugated structural EGCG and MT, MTE with small and uniform size is obtained by effectively hindering Ostwald ripening of MT. Noteworthily, MTE not only effectively avoids the inadvertent side effects of phototoxicity during transport thank to the ability of reactive oxygen species (ROS) scavenging, but also achieves two-pathway augmented superior phototherapy: (1) enhancing photodynamic therapy (PDT) via inhibiting the expression of anti-apoptosis protein surviving; (2) achieving adjuvant mild-temperature laser interstitial thermal therapy (LITT) via reducing the tumor thermoresistance on account that MTE inhibits the overexpression of HSP 70 and HSP 90. This research not only offers a facile strategy to construct multicomponent nanoplatforms but also provides a new pathway for efficient and low-toxicity phototherapy, which is beneficial to the future clinical application.
Keyphrases
- photodynamic therapy
- reactive oxygen species
- fluorescence imaging
- oxidative stress
- heat shock protein
- cell death
- heat shock
- heat stress
- cell proliferation
- dna damage
- stem cells
- transcription factor
- binding protein
- signaling pathway
- cancer therapy
- cell cycle arrest
- current status
- mesenchymal stem cells
- protein protein
- amino acid
- bone marrow
- water soluble