Micelles of zinc protoporphyrin conjugated to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer for imaging and light-induced antitumor effects in vivo

0388150 - ÚMCH 2013 RIV NL eng J - Článek v odborném periodiku
Nakamura, H. - Liao, L. - Hitaka, Y. - Tsukigawa, K. - Šubr, Vladimír - Fang, J. - Ulbrich, Karel - Maeda, H.
Micelles of zinc protoporphyrin conjugated to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer for imaging and light-induced antitumor effects in vivo.
Journal of Controlled Release. Roč. 165, č. 3 (2013), s. 191-198. ISSN 0168-3659. E-ISSN 1873-4995
Grant CEP: GA AV ČR IAAX00500803
Výzkumný záměr: CEZ:AV0Z40500505
Institucionální podpora: RVO:61389013
Klíčová slova: fluorescence imaging * fluorescent nanoprobe * singlet oxygen
Kód oboru RIV: CD - Makromolekulární chemie
Impakt faktor: 7.261, rok: 2013

We synthesized N-(2-hydroxypropyl)methacrylamide polymer conjugated with zinc protoporphyrin (HPMA-ZnPP) and evaluated its application for tumor detection by imaging and treatment by light exposure using in mouse sarcoma model. To characterize HPMA-ZnPP micelle, we measured its micellar size, surface charge, stability, photochemical, biochemical properties and tissue distribution. In vivo anti-tumor effect and fluorescence imaging were carried out to validate the tumor selective accumulation and therapeutic effect by inducing singlet oxygen by light exposure. HPMA-ZnPP was highly water soluble and formed micelles spontaneously having hydrophobic clustered head group of ZnPP, in aqueous solution, with a hydrodynamic diameter of 82.8 ± 41.8 nm and zeta-potential of + 1.12 mV. HPMA-ZnPP had a long plasma half-life and effectively and selectively accumulated in tumors. Although HPMA-ZnPP alone had no toxicity in S-180 tumor-bearing mice, light-irradiation significantly suppressed tumor growth in vivo, similar to the cytotoxicity to HeLa cells in vitro upon endoscopic light-irradiation. HPMA-ZnPP can visualize tumors by fluorescence after i.v. injection, which suggests that this micelle may be useful for both tumor imaging and therapy. Here we describe preparation of a new fluorescence nanoprobe that is useful for simultaneous tumor imaging and treatment, and application to fluorescence endoscopy is now at visible distance.
Trvalý link: http://hdl.handle.net/11104/0217239