Chlorin-e6 loaded mesoporous silica nanoparticles for photodynamic therapy of pancreatic cancer

摘要

The survival rate for patients diagnosed with pancreatic cancer is dismal. Current intravenous single and combination chemotherapeutics lack efficacy and cause harmful side effects and patient discomfort. Use of nanoparticles to deliver chemotherapeutics has aroused significant research interest, due to their higher specificity, efficacy and low toxicity. This thesis addressed the challenges of conventional therapy by designing a sub-150nm mesoporous silica nanoparticle drug delivery system, for remotely triggered photodynamic therapy (PDT). The MSNPs synthesized were spherical, porous, non-cytotoxic, and of average size of 120nm. Chlorin-e6 was loaded into the particles with an average loading efficiency of 75%, for a 25% by wt. loading capacity. Drug release studies conducted over a duration of 48hours showed a controlled release, with a total of 60% released at the end of two days. Efficacy studies, under irradiated and non-irradiated conditions, for free drug and the loaded -nanoparticle, on AsPC-1 pancreatic cancer monolayers were carried out. Photodynamic therapy was more effective at higher concentrations and light doses. The irradiated MSN-Ce6 particles showed significantly higher cell killing as compared to the free Ce6 at all concentrations. However, at higher light doses, light toxicity was observed. Higher concentrations showed dark toxicity. Fluorescence imaging showed higher uptake of Ce6 drug from the loaded nanoparticles, than the free drug.