title: Photodynamic detection of oral cancers with high-performance chitosan-based nanoparticles.
abstract: Oral cancer, a subtype of head and neck cancer, is one of the leading causes of cancer death and is difficult to detect in the early stages. Improved methods of detecting primary oral lesions during endoscopy would significantly improve cancer survival rates. Here we report a high-performance nanoparticle for photodynamic detection of oral cancer. Succinate-modified chitosan (SCHI) is physically complexed with folic-acid-modified chitosan to form nanoparticles with a high drug loading efficiency and to improve drug release in the cellular lysosome. The z-average diameter and zeta potential of the prepared nanoparticles (fSCN) were 110.0 nm and 18.6 mV, respectively, enough to keep the nanoparticles stable in aqueous suspension without aggregating. When loaded with 5-aminolaevulinic acid (5-ALA; 72.8% loading efficiency) in the prepared fSCNA, there were no significant differences between the fSCN and fSCNA in particle size or zeta potential. Moreover, the fSCNA nanoparticles were readily engulfed by oral cancer cells via folate-receptor-mediated endocytosis. The release of loaded 5-ALA in the lysosome was promoted by the reduced attraction intensity between chitosan and 5-ALA via the deprotonated SCHI molecules, which resulted in a higher accumulation of intracellular protoporphyrin IX (PpIX) for photodynamic detection. These results demonstrate that N-succinyl-chitosan-incorporated and folic-acid-conjugated chitosan nanoparticles are an excellent vector for oral-specific delivery of 5-ALA for fluorescent endoscopic detection.
authors.affiliation: Graduate Institute of Toxicology, College of Medicine, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Shu-Jyuan
authors.initials: SJ
authors.lastname: Yang
authors.forename: Cha-Fu
authors.initials: CF
authors.lastname: Lin
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
authors.forename: Ching-Ting
authors.initials: CT
authors.lastname: Tan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry*; D005260:Female; D005452:Fluoresceins / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry; D058972:Folic Acid Transporters / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism; D009368:Neoplasm Transplantation; D061848:Optical Imaging; D010316:Particle Size; D011524:Protoporphyrins / Q000378:metabolism; D013387:Succinic Anhydrides / Q000737:chemistry
chemical_list: D005452:Fluoresceins; D005456:Fluorescent Dyes; D058972:Folic Acid Transporters; D011524:Protoporphyrins; D013387:Succinic Anhydrides; C031801:succinic anhydride; D048271:Chitosan; D005492:Folic Acid; C028025:protoporphyrin IX; C007740:fluorexon