Facile synthesis of chitosan assisted multifunctional magnetic Fe3O4@SiO2@CS@pyropheophorbide-a fluorescent nanoparticles for photodynamic therapy†
Abstract
Novel chlorin photosensitizer pyropheophorbide-a (PPA) coated multifunctional magneto-fluorescent nanoparticles Fe3O4@SiO2@CS@PPA (MFCSPPA) about 50 nm in diameter were strategically designed and prepared for photodynamic therapy (PDT) based on the good solubility and magnetic targeting of Fe3O4@SiO2 nanoparticles, excellent biocompatibility and biodegradability of chitosan (CS) polymer, and the unique fluorescence and photodynamic activity of pyropheophorbide-a. In this work, we found that magneto-fluorescent MFCSPPA has high saturation magnetization of 23.7 emu gā1, and showed super-paramagnetic properties, good dispersion in alcohol and water, excellent water-solubility, improved biocompatibility and good photoluminescence properties. In addition, we demonstrated MFCSPPA mediated singlet oxygen production in solution conditions by using 1,3-diphenylisobenzofuran (DPBF) as a fluorescence detector. Moreover, the in vitro PDT activities against human HeLa cervical cancer cells were investigated by MTT assay. The phototoxicity experiments showed that MFCSPPA has strong photodynamic therapy activity and low dark toxicity, and the cancer cell viability was reduced to 18% after treatment with PDT. Phagocytosis of MFCSPPA experiments indicated that it could be successfully taken up to some extent by HeLa cells with a suitable lipo-hydro partition coefficient and biocompatibility. Acridine orange/ethidium bromide (AO/EB) double fluorescence staining suggested that the cells are all in a state of apoptosis or necrosis after PDT treatment for 6 h. In addition, we studied the formation of reactive oxygen species in HeLa cells after MFCSPPA-PDT treatment; the results suggested that type I and type II photodynamic reactions can occur simultaneously, yet type I photodynamic reactions have a slight edge over type II. The as-prepared magneto-fluorescent MFCSPPA nanoparticles are suitable for simultaneous PDT and medical fluorescence imaging.