Hyaluronic acid (HA) a biodegradable, biocompatible and nontoxic glycosaminoglycan has shown huge success in a variety of biomedical applications, including drug delivery, tissue engineering, and molecular imaging. One unique feature of HA relies in the active tumor targeting through selective interactions with specific receptors, such as CD44 and RHAMM, typically overexpressed on the surface membranes of various tumor cells. [1-2] Currently, several HA-drug conjugates are under preclinical/clinical study and many HA-based hybrid platforms are investigated to improve the anticancer therapy by targeting CD44-expressing cells. [3] Targeted PDT treatment implies selective accommodation of a photosensitiser (PS) in tumour sites and the subsequent light irradiation by optical fiber generating the reactive oxygen species (ROS) and in particular cytotoxic singlet oxygen (1O2). Here we report the design of nanoassemblies based on a cationic amphiphilic cyclodextrin (aCyD) carrier (SC12NH3 +Cl-), [4] entrapping pheophorbide (Pheo) as PS and finally decorated with hyaluronic acid sodium salt [5] to promote the internalization in cancer cells. HA@SC12NH3 +Cl-/Pheo nanoassemblies were prepared at different aCyD/HA mass ratios and complementary techniques such as UV-Vis absorption and steady-state fluorescence spectroscopy have been exploited to elucidate size, drug loading and to get insight on the PS aggregation behaviour. At selected CD/HA mass ratio, correspondently to the HA amount leading to a complete saturation of aCyD positive charges, nanoassemblies showed a hydrodynamic radius of ? 200 nm, a negative surface zetapotential and high Pheo loading and entrapment efficiency. Release studies of Pheo from the nanoassemblies were carried out in relevant biological media. Currently, biological evaluation of SC12NH3+Cl-@Pheo/HA on different cancer cell lines is in progress.
Cationic Amphiphilic Cyclodextrin Decorated with Hyaluronic Acid: a Novel Nanoassembly for targeted PDT
Roberto Zagami;Antonino Mazzaglia
2017
Abstract
Hyaluronic acid (HA) a biodegradable, biocompatible and nontoxic glycosaminoglycan has shown huge success in a variety of biomedical applications, including drug delivery, tissue engineering, and molecular imaging. One unique feature of HA relies in the active tumor targeting through selective interactions with specific receptors, such as CD44 and RHAMM, typically overexpressed on the surface membranes of various tumor cells. [1-2] Currently, several HA-drug conjugates are under preclinical/clinical study and many HA-based hybrid platforms are investigated to improve the anticancer therapy by targeting CD44-expressing cells. [3] Targeted PDT treatment implies selective accommodation of a photosensitiser (PS) in tumour sites and the subsequent light irradiation by optical fiber generating the reactive oxygen species (ROS) and in particular cytotoxic singlet oxygen (1O2). Here we report the design of nanoassemblies based on a cationic amphiphilic cyclodextrin (aCyD) carrier (SC12NH3 +Cl-), [4] entrapping pheophorbide (Pheo) as PS and finally decorated with hyaluronic acid sodium salt [5] to promote the internalization in cancer cells. HA@SC12NH3 +Cl-/Pheo nanoassemblies were prepared at different aCyD/HA mass ratios and complementary techniques such as UV-Vis absorption and steady-state fluorescence spectroscopy have been exploited to elucidate size, drug loading and to get insight on the PS aggregation behaviour. At selected CD/HA mass ratio, correspondently to the HA amount leading to a complete saturation of aCyD positive charges, nanoassemblies showed a hydrodynamic radius of ? 200 nm, a negative surface zetapotential and high Pheo loading and entrapment efficiency. Release studies of Pheo from the nanoassemblies were carried out in relevant biological media. Currently, biological evaluation of SC12NH3+Cl-@Pheo/HA on different cancer cell lines is in progress.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
