Small anticancer drug release by light

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Aiming to engineer simple, neutral, strongly amphiphilic photoactive nanoparticles (NPs) to specifically target cancer cell lysosomes for drug transport and light-controlled release, new conjugates of β-cyclodextrin with highly hydrophobic triphenylporphyrin bearing different alkyl chains, were synthesized. Although differently sized, all conjugates self-assemble into ~60 nm NPs in water and display similar photoactivity. The NPs target selectively the lysosomes of breast adenocarcinoma MCF-7 cells, embedding in vesicular membranes, as experiments with model liposomes indicate. Either empty or drug-loaded, the NPs lack dark toxicity for 48 h. They bind with differently structured anticancer drugs tamoxifen and gemcitabine as its N-adamantyl derivative. Red light irradiation of cells incubated with drug-loaded NPs results in major reduction of viability (>85 %) for 48 h displaying significant synergy of photo-chemotoxicity, as opposed to empty NPs, and to loaded non-irradiated NPs, in manifestation of photochemic internalization (PCI). This approach expands the field of PCI into different small molecule chemotherapeutics.

Stylianos Panagiotakis, Barbara Mavroidi, Alexandros Athanasopoulos, Antonio Ricardo Gonçalves, Loïc Bugnicourt-Moreira, Theo Regagnon, Nikos Boukos, George Charalambidis, Athanasios G. Coutsolelos, Mantas Grigalavicius, Theodossis A. Theodossiou, Kristian Berg, Catherine Ladavière, Maria Pelecanou, Konstantina Yannakopoulou (2023) Small anticancer drug release by light: Photochemical internalization of porphyrin-β-cyclodextrin nanoparticles. Carbohydrate Polymers 120579.

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