Application of nanoparticle in photodynamic diagnosis for colorectal cancer

摘要

Photodynamic medicine is a novel approach for cancer detection and treatment via different photosensitizers and suitable light source. The 5-Aminolevulinic acid (5-ALA) can be converted into protoporphyrin IX (PpIX) that can be utilized as a fluorescent probe for tumor detection, however, this biosynthetic pathway can also occur in intestinal normal flora, such as E. coli, which inevitably influences the efficacy of tumor detection. In this study, 5-ALA was encapsulated in nanoparticles to prevent uptake by E. coli. We mixed chitosan with sodium tripolyphosphate (STPP) to prepare chitosan nanoparticles (CN) — by ionic gelation method. Chitosan nanoparticle loaded with 5-ALA (CN-A) were prepared by the same method. The size and zeta potential of CN and CN-A were measured by transmission electron microscope and zetasizer, respectively. CN.and CN-A were both at the range of 60～110 nm in size, depending on the pH value of STPP solution and 5-ALA solution. When the pH value of STPP solution and 5-ALA solution increased, the nanoparticle size of CN and CN-A increased. The optimal 5-ALA loading efficiency for CN-A approximated 80%. Bioassy of CN-A for Caco-2 colon cancer cell and E. coli uptake was done, and the result revealed that Caco-2 colon cancer cells could uptake the CN-A and convert the loaded 5-ALA into PpIX which emitted red fluorescence when excited by the light with specific wave-length , whereas E. coli showed no such activity. This result implied that chitosan can exclude the influence of normal flora inside the gut and serves as an ideal vector of colon-specific drug delivery system. According to this concept, we designed a novel photodynamic detection system to enhance the accuracy of endoscopic diagnosis for early colorectal cancer.