Amphiphilic cyclodextrins (aCD) are an interesting class of carrier systems which, recently, were proposed to deliver porphyrinoids and anticancer drugs or combined dose of both for dual potential application in PDT and anticancer therapy [1-2]. Generally, the design of supramolecular complexes between nanoaggregates based on aCD and useful photosensitizers (PSs) aims to preserve the PDT efficacy of PS, reducing the tendency of PS to self-aggregate, without affecting the quantum yield of singlet oxygen (1O2) production, and, not less importantly, minimizing dark toxicity, by optimizing photostability, thus reducing photosensitization effects. Here we focus on nanoassemblies between a non-ionic aCD (heptakis(2-O-oligo(ethyleneoxide)-6-hexylthio)-?-CD, SC6OH) and a novel synthesized halo-alkyl tailored iodinated BODIPY dyes, a class of molecules which recently have been successfully proposed as a valid alternative to porphyrinoids for their high photodynamic effectiveness [3]. Nanoassemblies of BODIPY/aCD (BL01I@SC6OH) were prepared in different aqueous media at 1:2 molar ratio by evaporation of mixed organic film of aCD and BODIPY, hydration and sonication. The supramolecular assemblies display a hydrodynamic diameter DH of ? 250 nm, ?-potential of ? -25 mV and are fairly stable within 4 days in ultrapure water, PBS (10 mM, pH= 7.4) and NaCl solutions (0.9 %). Taking advantage of emissive properties of the not-iodinated BODIPY analogue (BL01), nanoassemblies based on aCD and BL01 were investigated as model system to get insight on entanglement of BODIPY in the amphiphile and its aggregation behavior. In summary, our evidence points out that BODIPY is well-entrapped in monomeric form (? ? 6.5 ns) within the colloidal carriers, showing a long rotation correlation time (?R > 20 ns). In addition, the highly fluorescent system BL01@SC6OH is easily detectable in cytoplasmatic region of HCT116 cell lines, pointing to the remarkable intracellular localization of this class of PS, comparable to free BODIPY. On the same cell lines, BL01I-loaded aCD shows significant photokilling effect, which can be time-controlled by cyclodextrin carrier modulating the BODIPY cell uptake. Altogether, our results agree with the feasibility of these systems as promising novel tools in PDT.
Supramolecular Assemblies Based on Bodipy/amphiphilic Cyclodextrin as Nanophototherapeutics with PDT Efficacy
R Zagami;G Sortino;A Mazzaglia
2018
Abstract
Amphiphilic cyclodextrins (aCD) are an interesting class of carrier systems which, recently, were proposed to deliver porphyrinoids and anticancer drugs or combined dose of both for dual potential application in PDT and anticancer therapy [1-2]. Generally, the design of supramolecular complexes between nanoaggregates based on aCD and useful photosensitizers (PSs) aims to preserve the PDT efficacy of PS, reducing the tendency of PS to self-aggregate, without affecting the quantum yield of singlet oxygen (1O2) production, and, not less importantly, minimizing dark toxicity, by optimizing photostability, thus reducing photosensitization effects. Here we focus on nanoassemblies between a non-ionic aCD (heptakis(2-O-oligo(ethyleneoxide)-6-hexylthio)-?-CD, SC6OH) and a novel synthesized halo-alkyl tailored iodinated BODIPY dyes, a class of molecules which recently have been successfully proposed as a valid alternative to porphyrinoids for their high photodynamic effectiveness [3]. Nanoassemblies of BODIPY/aCD (BL01I@SC6OH) were prepared in different aqueous media at 1:2 molar ratio by evaporation of mixed organic film of aCD and BODIPY, hydration and sonication. The supramolecular assemblies display a hydrodynamic diameter DH of ? 250 nm, ?-potential of ? -25 mV and are fairly stable within 4 days in ultrapure water, PBS (10 mM, pH= 7.4) and NaCl solutions (0.9 %). Taking advantage of emissive properties of the not-iodinated BODIPY analogue (BL01), nanoassemblies based on aCD and BL01 were investigated as model system to get insight on entanglement of BODIPY in the amphiphile and its aggregation behavior. In summary, our evidence points out that BODIPY is well-entrapped in monomeric form (? ? 6.5 ns) within the colloidal carriers, showing a long rotation correlation time (?R > 20 ns). In addition, the highly fluorescent system BL01@SC6OH is easily detectable in cytoplasmatic region of HCT116 cell lines, pointing to the remarkable intracellular localization of this class of PS, comparable to free BODIPY. On the same cell lines, BL01I-loaded aCD shows significant photokilling effect, which can be time-controlled by cyclodextrin carrier modulating the BODIPY cell uptake. Altogether, our results agree with the feasibility of these systems as promising novel tools in PDT.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
