Gold nanoprisms as potential delivery agents for photodynamic therapy photosensitizers

Shton I.O.1, Yermak P.V.2, Chevichalova A.3, Estrela-Llopis V.3, Gamaleia N.F.1

I. Shton1, P. Yermak1, A. Chevichalova2, V. Estrela-Llopis2, N. Gamaleia1

1R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine

2F.D. Ovcharenko Institute of Biocolloidal Chemistry, NAS of Ukraine, Kyiv, Ukraine

gamaleia@onconet.kiev.ua victorio.estrela@gmail.com

Introduction: It is well known, that properties of nanomaterial strongly depend on particle shape and size. Gold nanospheres have already become an object for targeted drug delivery research. However, recently more attention is drawn to nanoparticles with different geometrical parameters, particularly nanoprisms. Such nanocarriers can be successfully applied as delivery agents for photodynamic therapy (PDT). One of the most questionable aspects of this approach is nanoparticle interaction with different cell types. Aim: To assess the gold nanoprism toxicity and ability to accumulate in malignant and normal cells in vitro and to evaluate the effectiveness of PDT in vivo using Fotolon-nanoprism composite as a photosensitizer. Methods: Human glioblastoma cell line A172 (kindly provided by Dr. S.P. Sydorenko), human Burkitt’s lymphoma cell line Namalwa, peritoneal mouse macrophages, normal human monocytes and lymphocytes were used for studies in vitro. Mice C57Bl/6 with transplanted Lewis lung carcinoma were used in PDT experiments. Nanoprisms with average diameter of 88.3 nm (determined by DLS analyzer «Analysette 12 DynaSizer”, «Fritsch”, Germany) were stabilized with chlorella polysaccharides. Chlorine e6-based drug Fotolon (RUE Belmedpreparaty, Belarus) was used as a photosensitizer. Accumulation of nanoprisms in target cells was studied using dark-field microscopy. Cell viability in toxicity tests was assessed by trypan blue dye exclusion method. In vivo effectiveness of gold nanoprisms was studied by assessment of tumor growth inhibition. Results: Cultured cells were incubated with nanoprisms at concentrations of 10 or 100 μg/ml for 1 hour in accumulation studies and 1 or 24 hours in toxicity stu­dies. Dark-field microscopy studies of Namalwa cells showed that the nanoparticles accumulate mostly on the cell surface. Apparently, they do not penetrate cell membrane. Normal human lymphocytes do not accumulate nanoprisms even at concentration 100 μg/ml. On the contrary, treatment of peritoneal mouse macrophages and human blood monocytes, as well as human glioblastoma cells A172 with gold nanoprisms leads to nanoprism accumulation in cytoplasm. Gold nanoprisms were not toxic to normal human lymphocytes in both concentrations tested (10 and 100 μg/ml). As to Namalwa cell line, viability of the cells, treated with nanoprisms, decreased slightly (by 6–8%) only after their incubation with maximal nanoparticle concentration. Evaluation of Fotolon-nanoprism composite activity in PDT tests in vivo showed inhibition of Lewis lung carcinoma growth to 70% versus 32% in the group of animals treated with free Fotolon. Conclusions: 1. Gold nanoprisms are relatively nontoxic to cells. 2. Nanoprisms aggregated on the surface of transformed lymphocytes and did not aggregate on the surface of normal cells. 3. The nanoparticles were absorbed mostly by phagocytic cells. 4. Antitumor photodynamic activity of Fotolon-nanoprism composite exceeded such of the free Fotolon more than twice.

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