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Liposomal Salvianolic Acid B Enhances ALA-PDT in Oral Leucoplakia via ROS and AKT/mTOR Signalling
Ying Zhang1, Xiaoxian Zhao1, Xinyi Han1
1Department of Oral Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai, China.
Salvianolic acid B (SalB) in a nano-photosensitizer formulation enhances photodynamic therapy (PDT) for oral leucoplakia (OLK). This approach modulates reactive oxygen species (ROS) and the PI3K/AKT/mTOR pathway, offering improved clinical strategies.
Area of Science:
- Biomedical Engineering
- Pharmacology
- Oncology
Background:
- Salvianolic acid B (SalB), derived from Salvia miltiorrhiza Bunge, exhibits anti-tumour properties.
- Photodynamic therapy (PDT) using SalB-loaded nanocarriers showed promise against oral leucoplakia (OLK) and oral cancer cells in vitro.
- Further investigation into the mechanisms and in vivo efficacy of this SalB-based PDT formulation is warranted.
Purpose of the Study:
- To explore the underlying mechanisms of SalB-loaded nanocarrier-mediated PDT for OLK.
- To evaluate the in vivo effects of a novel nano-photosensitizer formulation (nano-SalB-ALA) in an OLK mouse model.
- To determine the impact of nano-SalB-ALA PDT on the PI3K/AKT/mTOR signaling pathway.
Main Methods:
- Liposomes were formulated with varying concentrations of SalB and 5-aminolevulinic acid (ALA) to create nano-photosensitizers (nano-SalB-ALA).
- Reactive oxygen species (ROS) levels were assessed using DCFH-DA staining in Cal27 and Leuk1 cells.
- Intracellular liposome distribution was visualized via confocal laser scanning microscopy (CLSM), and PI3K/AKT/mTOR signaling proteins were analyzed by Western blot.
- An in vivo study utilized a 4NQO-induced OLK mouse model to assess therapeutic effects.
Main Results:
- The nano-SalB10-ALA250 formulation demonstrated significant intracellular ROS generation and effectively inhibited the PI3K/AKT/mTOR signaling pathway in vitro.
- In vivo studies using the OLK mouse model confirmed that nano-SalB10-ALA250 PDT suppressed the PI3K/AKT/mTOR signaling pathway.
- The selected formulation (nano-SalB10-ALA250) exhibited the most pronounced effects on ROS levels and pathway inhibition.
Conclusions:
- Nano-SalB-ALA PDT effectively modulates ROS levels and inhibits the PI3K/AKT/mTOR signaling pathway in both in vitro and in vivo models of OLK.
- SalB, when formulated as a nano-photosensitizer, enhances PDT efficacy for OLK.
- This approach offers potential new strategies for improving clinical PDT outcomes in OLK treatment.
