Combining Photodynamic Therapy and Chemotherapy: Improving Breast Cancer Treatment with Nanotechnology

Author(s)

Candido, Natalia Maria ^[1] ; de Melo, Maryanne Trafani ^[2] ; Franchi, Leonardo Pereira ^[2] ; Primo, Fernando Lucas ^[3] ; Tedesco, Antonio Claudio ^[2] ; Rahal, Paula ^[1] ; Calmon, Marilia Freitas ^[1]

Affiliation

^[1] UNESP, Inst Biosci Language & Literature & Exact Sci IBI, Dept Biol, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Philosophy Sci & Letters Ribeirao Preto FFCLR, Dept Chem, BR-14040900 Ribeirao Preto, SP - Brazil

^[3] UNESP, Fac Pharmaceut Sci Araraquara FCF, Dept Bioproc & Biotechnol, BR-14800903 Araraquara, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF BIOMEDICAL NANOTECHNOLOGY; v. 14, n. 5, p. 994-1008, MAY 2018.
• Web of Science Citations: 5

Abstract

Nanomedical approaches are the major transforming factor in cancer therapies. Based on important previous works in the field of drug delivery nanomaterials, recent years have brought a broad array of new and improved intelligent nanoscale platforms that are suited to deliver drugs. In this context, the purpose of this study was to investigate the action of different nanoemulsions designed to encapsulate chloroaluminum phthalocyanine, a hydrophobic photosensitizer used in photodynamic therapy, and doxorubicin, a well-known chemotherapeutic agent used to treat aggressive breast cancer cells. The mean nanostructured system size ranged from 170.8 to 181.0 nm, and the nanoemulsions presented spherical morphology. All formulations exhibited negative zeta potential values (-68.7 to -75.0 mV) and suitable polydispersity values (0.20 to 0.28), explaining their colloidal stability up to three months. Murine breast cancer cells (4T1) were incubated with nanoemulsions for three hours at various concentrations and were subjected to cell viability tests to find the concentration dependence profile. Thereafter, the in vitro phototoxic effect was evaluated in the presence of the visible laser light irradiation. Less than 10% of 4T1 viable cells were observed when photodynamic therapy and chemotherapy were combined at a 1.0 J.cm(-2) laser light dose with 1.0 mu M phthalocyanine and 0.5 mu M doxorubicin. The cell death assay and cell cycle arrest analysis confirmed the therapy efficiency demonstrating an increase in the apoptosis rate and in the cell cycle arrest on G2. Additionally, 15 genes related to apoptosis and 25 target genes of anti-cancer drugs were overexpressed. Four genes related to apoptosis and four target genes of anti-cancer drugs were downregulated in 4T1 cells after treatment with nanoemulsion with phthalocyanine and doxorubicin associated with photodynamic therapy. Thus, the nanoemulsions loaded with phthalocyanine and doxorubicin presented appropriate physical stability, improved photophysical properties, and remarkable activity in vitro to be considered as promising formulations for photodynamic therapy and chemotherapeutic use in breast cancer treatment. (AU)

• FAPESP's process: 15/16660-5 - Analysis of the nanoemulsions associated with photodynamic therapy in the treatment of breast cancer
• Grantee: Marilia de Freitas Calmon
• Support Opportunities: Regular Research Grants