Enhanced breast cancer targeting ability of Ce6/p18-4-conjugated spherical nanohybrids for photodynamic therapy

Abstract

Event Abstract Back to Event Enhanced breast cancer targeting ability of Ce6/p18-4-conjugated spherical nanohybrids for photodynamic therapy Young-Jin Kim1 1 Catholic University of Daegu, Department of Biomedical Engineering, Korea Introduction: Breast cancer is the most common cancer in women representing >30% of malignancies in women. Major drawbacks of current cancer therapies are side effects and low specificity for tumor cells. To improve the specific uptake of therapeutic agents in the tumor, different strategies have been pursued. One of them is the use of molecular addresses for tumor targeting[1]. However, the size of intact antibody molecules results in a limited tumor penetration and a slow clearance from the circulation, which decreases the tumor-to-blood ratio. As an alternative to antibodies, recent efforts to identify new targeting molecules on carcinomas and metastases have focused on the use of peptides[2]. Peptides possess pharmacokinetic properties that make them ideal shuttles for tumor targeting, as they are smaller and usually characterized by rapid clearance from blood and nontarget tissues and high uptake into target tissues. Therefore, in the present study, p18-4 peptide was used as a targeting ligand, and multifunctional octamaleic acid-POSS was used for the conjugation of p 18-4 peptide and chlorine e6 (Ce6) for photodynamic therapy (PDT). Materials and Methods: A synthesis of Ce6/peptide ligand (p18-4)-conjugated POSS (POSS-p18-4-Ce6) nanohybrids is as follows. Chlorine e6 (Ce6) was first dissolved in DMSO, followed by adding EDC and NHS to activate carboxylic groups. After adding ethylene diamine in distilled water to the mixture, the reaction was allowed to produce aminaterd Ce6. To produce POSS-p18-4-Ce6, octamaleic acid-POSS, EDC and NHS were dissolved in DMSO. Then aminated Ce6 and p18-4 peptide (WxEAAYQrFL) were added to the mixture. The reactants were stirred at room temperature for 24 h to synthesize POSS-p18-4-Ce6 nanohybrids. Results and Discussion: p18-4 peptide/Ce6-conjugated spherical POSS (POSS-p18-4-Ce6) nanohybrids were first synthesized and the structure of the POPCe nanohybrids was determined by 1H-NMR spectroscopy. To investigate the cytotoxicity, the intracellular uptake of free Ce6 and POSS-p18-4-Ce6 into cancer cells was first assessed by confocal laser scaning microscope (CLSM). POSS-p18-4-Ce6 exhibited enhanced PDT efficiency. To confirm the targeting efficacy of p18-4 peptide, human breast cancer cell line (MCF-7) was used. In addition, two human normal cell lines, MCF-10A (normal human mammary epithelial cell) and HUVEC (normal human vascular endothelial cell), were used as control. The POSS-p18-4-Ce6 nanohybrids showed amplified phototoxicity and the targeting efficacy of these nanohybrids on MCF-7 cells was higher than those on other cancer cell lines. However, in MCF-10A and HUVEC cell lines, there was no significant effect even under irradiation condition, implying that POSS-p18-4-Ce6 nanohybrid system might be potentially applicable in PDT. Conclusion: Nanostructured materials have enhanced the intracellular uptake of photosensitizers due to improving the water-solubility of photosensitizers. In the present study, POSS-p18-4-Ce6 nanohybrids were successfully developed by one-step reaction, which showed high phototoxicity due to mostly apoptotic cell death. Based on these results, the POSS-p18-4-Ce6 nanohybrids may contribute to the development of a new generation of photosensitizer carriers for enhanced PDT treatment of cancers. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2013R1A1A2006665)