Adipogenic differentiation of murine bone marrow mesenchymal stem cells induced by visible light via photo- induced biomodulation.

BACKGROUND: Bone marrow mesenchymal stem cells (BM-MSCs) are undifferentiated cells that can proliferate and differentiate into specialized cells for tissue self-repair. Low-level laser (LLL) can induce biomodulatory effects such as cellular proliferation, differentiation, and migration. We investigated the biomodulatory effects of the photoactive compound chloroaluminum phthalocyanine nanoemulsion (AlClPc/NE) on the adipogenic differentiation of BM-MSCs, when combined with LLL (AlClPc/NE-LLL). METHODS: The BM-MSCs used in this work were isolated from green fluorescent protein-positive (GFP+) C57BL6 mice. Cells were first treated with AlClPc/NE, a well-designed photoactive nano-drug and were then subjected to in vitro expansion, morphological and immunophenotypic characterization, and cellular cytotoxicity analysis. Subsequently, BM-MSCs were induced to differentiate into adipocytes by photo-induced biomodulation with AlClPc/NE-LLL. RESULTS: Our results showed that the isolated cell population was consistent with murine BM-MSCs. The cellular cytotoxicity analysis revealed that the optimal nanoemulsion dose to induce BM-MSC biomodulation was 5.0 µmol/L. Twenty-four hours following treatment with AlClPc/NE, BM-MSC were subjected to visible light irradiation of 20 mJ/cm2 at 670 nm. Six days after photo-induced biomodulation, cells maintained high GFP expression level, and expressed detectable mRNA levels of adipogenic genes (lipoprotein lipase and PPARγ); formation of lipid vacuoles was observed, and the cells did not show any tumorigenic potential in vivo. CONCLUSIONS: Our results indicated that photo-induced biomodulation via visible light using AlClPc/NE and LLL can induce adipogenic differentiation of murine BM-MSCs. Therefore, cell therapy with BM-MSCs and photo-induced biomodulation may contribute to the development of new therapeutic strategies that are faster and more effective than traditional methods to trigger MSC differentiation.

Photodynamic process induced by chloro-aluminum phthalocyanine nanoemulsion in glioblastoma.

BACKGROUND: Glioblastoma multiforme (GBM) is a tumor characterized by rapid cell proliferation and migration. GBM constitutes the most aggressive and deadly type of brain tumor and is classified into several subtypes that show high resistance to conventional therapies. There are currently no curative treatments for malignant glioma despite the numerous advances in surgical techniques, radiotherapy, and chemotherapy. Therefore, alternative approaches are required to improve GBM treatment. METHODS: Our study proposes the use of photodynamic therapy (PDT) for GBM treatment, which uses chloro-aluminum phthalocyanine (AlClPc) encapsulated in a new drug delivery system (DDS) and designed as a nanoemulsion (AlClPc/NE). The optimal dark non-cytotoxic AlClPc/NE concentration for the U87 MG glioma cell model and the most suitable laser light intensity for irradiation were determined. Experimental U87 MG cancer cells were analyzed via MTT cell viability assay. Cellular localization of AlClPc, morphological changes, and cell death via the necrotic and apoptotic pathways were also evaluated. RESULTS: AlClPc remained in the cytoplasmic region at 24h after administration. Additionally, treatment with 1.0µmol/L AlClPc under light irradiation at doses lower than 140mJ/cm resulted in morphological changes with 50±6% cell death (p<0.05). Moreover, 20±2% of U87 MG cells underwent cell death via the necrotic pathway. Measurement of Caspase-9 and -3 activities also suggested that cells underwent apoptosis. Taken together, these results indicate that AlClPc/NE-PDT can be used in the treatment of glioblastoma by inducing necrotic and apoptotic cell death. CONCLUSIONS: Our findings suggest that AlClPc/NE-PDT induces cell death in U87 MG cells in a dose-dependent manner and could thus serve as an effective adjuvant treatment for malignant glioma. AlClPc/NE-PDT utilizes a low dose of visible light and can be used in combination with other classic GBM treatment approaches, such as a combination of chemotherapy and surgery.