PP131: Development of cell internalizable magnetite nanoparticle as a novel in vivo OSCC combined therapy.

Purpose: Traditional chemotherapies are still far from satisfactory due to the development of drug resistance and side effects derived from non-specific targeting of healthy normal cells. Recent reports suggest that combined physical and chemical approaches in cancer therapy may have synergistic advantage such as hyperthermia and chemotherapy especially when both approaches are delivered under synchronized manner. In addition, previous studies reported that CD44 plays multiple functions in oral squamous cell carcinoma (OSCC) progression. CD44 can be triggered to internalize by extracellular matrix or antibody and to form the transcriptional complex. Their nuclear translocation could turn on cancer reprogramming genes. In this study, we use this internalization pathway to design a novel hyperthermo-chemotherapy that shuttled the oligonucleotide magnetite nanoparticles from cell membrane to the nucleus. Materials and methods: The designed nanoparticle includes a high-saturation magnetization (94emu/g) magnetite nanocrystals core conjugated with polynucleotide loaded with 5-fluorouracil (5-FU) shells and anti-CD44 mAb. We used two OSCC cell lines (OEC-M1 and HSC-3) and two normal cells (NHOK and HUVEC) in targeting internalization study. We utilized radiofrequency (RF) to induce magnetic hyperthermia (MHT) and evaluated the efficacy in HSC-3 bearing NOD/SCID mice. Results: In the in vitro study, we discovered internalization of the membrane CD44 in OSCC cells significantly high than normal cells. The cytotoxicity text showed OSCC cells present significantly lower than normal cells after nanoparticle treatment. We further confirmed nanoparticle treatment combined RF can decrease cell viability in a time-dependent manner. The in vivo results showed only a single dose I.V. injection combined RF treatment caused tumor cell damage and decrease in tumor volume. Conclusion: This novel therapy consists of two stages: First, the CD44 induced internalization of the nanoparticle could augment both extra-and intracellular MHT by RF in oral cancer. Second, the 5-FU released during MHT provides effective chemotherapy to retard tumor re-progression. We anticipate such achievements could inspire further nano drug delivery strategy to advance oral cancer therapeutics. [Copyright &y& Elsevier]