RESUMO
A comparative study of in vitro anti-cancer photodynamic activities of three-component zinc-tetraphenylporphyrin photosensitizer/dextran-graft-polyacrylamide copolymer/Au(Ag) nanoparticle (ZnTPP/D-g-PAA/Au(Ag)NP) nanohybrids on LNCaP prostate cancer cells was carried out under 420 nm light irradiation with low power. A significant cytotoxic effect was revealed for both ZnTPP/D-g-PAA/AgNP and ZnTPP/D-g-PAA/AuNP nanohybrids, where ZnTPP/D-g-PAA/AgNP nanohybrids exhibited considerably higher anticancer activity (82%) compared to ZnTPP/D-g-PAA/AuNP nanohybrids (45%). The higher activity of silver-containing nanohybrids is rationalized based on two factors. The first factor is the resonance of 420 nm light with a absorption Soret peak of the ZnTPP photosensitizer and a localized surface plasmon mode in Ag nanoparticles. Correspondingly, the plasmon enhancement of reactive oxygen species photogeneration by ZnTPP molecules was considerably higher for the nanohybrid containing silver compared to the one containing gold. The second factor is the higher cytotoxicity of Ag nanoparticles compared to Au ones. The study results prove the high potential of D-g-PAA/Ag(Au)NP nanohybrids combined with 420 nm light irradiation with low power in the photodynamic treatment of prostate cancer.
RESUMO
Introduction: Cancer chemotherapy faces two major challenges - high toxicity of active substances and tumor resistance to drugs. Low toxic nanocarriers in combination with anticancer agents can significantly increase the effectiveness of therapy. Modern advances in nanotechnology make it easy to create materials with the necessary physical and chemical properties. Methods: Two hybrid nanosystems of dextran-polyacrylamide/ zinc oxide nanoparticles (D-PAA/ZnO NPs) were synthesized in aqueous solution with zinc sulphate (D-PAA/ZnO NPs (SO42-)) and zinc acetate (D-PAA/ZnO NPs (-OAc)). The light absorption, fluorescence, dynamic light scattering and transmission electron microscopy for nanocomposite characterization were used. MTT, neutral red uptake and scratch assays were selected as fibroblasts cytotoxicity assays. Cytotoxicity was tested in vitro for normal fibroblasts, MAEC, prostate (LNCaP, PC-3, DU-145) and breast (MDA-MB-231, MCF-7) cancer cells lines. Immunocytochemical methods were used for detection of Ki-67, p53, Bcl-2, Bax, e-cadherin, N-cadherin and CD44 expression. Acridine orange was used to detect morphological changes in cells. Results: The radius of ZnO NPs (SO42-) was 1.5 nm and ZnO NPs (-OAc) was 2 nm. The nanosystems were low-toxic to fibroblasts, MAEC. Cells in the last stages of apoptosis with the formation of apoptotic bodies were detected for all investigated cancer cell lines. Proapoptotic proteins expression in cancer cells indicates an apoptotic death. Increased expression of E-cadherin and N-cadherin was registered for cancer cells line LNCaP, PC-3, DU-145 and MCF-7 after 48 h incubation with D-PAA/ZnO NPs (SO42-). Conclusion: The nanosystems were low-toxic to fibroblasts, MAEC. The D-PAA/ZnO NPs nanosystem synthesized using zinc sulphate demonstrates high cytotoxicity due to destruction of various types of cancer cells in vitro and potentially increases adhesion between cells. Thus, our findings indicate the selective cytotoxicity of D-PAA/ZnO NPs against cancer cells and can be potentially used for cancer treatment.
