Abstract
Titanium dioxide (TiO2) has attracted wide attention as a potential photosensitizer (PS) in photodynamic therapy (PDT). However, bare TiO2 can only be excited by ultraviolet illumination, and it lacks specific targeting ligands, which largely impede its application. In our study, we produced nitrogen-doped TiO2 and linked it with an effective cancer cell targeting agent, folic acid (FA), to obtain N-TiO2-FA nanoconjugates. Characterization of N-TiO2-FA included Zeta potential, absorption spectra and thermogravimetric analysis. The results showed that N-TiO2-FA was successfully produced and it possessed better dispersibility in aqueous solution than unmodified TiO2. The N-TiO2-FA was incubated with human nasopharyngeal carcinoma (KB) and human pulmonary adenocarcinoma (A549) cells. The KB cells that overexpress folate receptors (FR) on cell membranes were used as FR-positive cancer cells, while A549 cells were used as FR-negative cells. Laser scanning confocal microscopy results showed that KB cells had a higher uptake efficiency of N-TiO2-FA, which was about twice that of A549 cells. Finally, N-TiO2-FA is of no cytotoxicity, and has a better photokilling effect on KB cells under visible light irradiation. In conclusion, N-TiO2-FA can be as high-value as a PS in cancer targeting PDT.
Highlights
Photodynamic therapy (PDT) based on the photochemical reactions of photosensitizer (PS) is a noninvasive and mild medical treatment for cancer diseases [1–4]
The chemical agents used in the conjugation of folic acid on TiO2 NPs were folic acid (FA, ě97%, Sigma-Aldrich), dimethyl sulfoxide (DMSO, ě99.7%, Sigma-Aldrich), 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 99%, Sigma-Aldrich), and N-Hydroxysuccinimide (NHS, 99%, Sigma-Aldrich)
Zeta potential results showed that nitrogen-doping TiO2 (N-TiO2)-Folic acid (FA) had a negative Zeta potential and possessed good dispersibility
Summary
Photodynamic therapy (PDT) based on the photochemical reactions of photosensitizer (PS) is a noninvasive and mild medical treatment for cancer diseases [1–4]. TiO2 has attracted more attention as a potential PS in PDT due to its high chemical stability, excellent oxidation capability and low toxicity [8–10]. To enhance the visible light absorption of TiO2, various attempts have been made by dye-adsorbed [11,12] or doping methods [13,14]. A major challenge for the application of TiO2 in PDT is its lack of specific targeting ligands. To improve the cancer cellular uptake of TiO2 NPs, specific ligands, such as monoclonal antibodies, peptides and aptamers binding to specific proteins or surface antigens, could be coupled with TiO2 NPs. For example, it has been found that folate receptor (FR) is overexpressed on the surfaces of many human tumor cells, whereas it expresses little on the Nanomaterials 2016, 6, 113 surface of normal cells [15,16]. Agoltohdoutugmhothr emuasrekeorf fFoAr ttoartgaertginetgFtRreaotvmere-netxpinrePsDseTd. tAulmthoorucgehlls wertehsetuudsieedoifn FdAepttho fotarrvgaertioFuRs noavneorm-exapterreisaslesdsutcuhmaosrZnceOllsnawnoerpearstitculdesie[d17i]nanddepAtuh nfaonrorvoadriso[u1s8], FA nfuancotmioantearliazlesdsTuicOh2aNs ZPnsOwinthaneonphaartnicleeds v[1is7i]balendligAhut anbasnoorrpotdios n[1h8a],sFnAotfubneectnioenxaplilzoerdedT.iROe2 cNenPtsly, thewLieteh Wenehna-nCcheidenvitseibamle lmigohdt iafibesdorFpAtioonnhTaisOn2oNt Pbese, nanedxpulosereddt.hReeocebntatliyn,etdheFALe/eTWiOe2na-Cs haiePnS tuenamder
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