Small anticancer drug release by light: Photochemical internalization of porphyrin-?-cyclodextrin nanoparticles

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 beta-cyclodextrin with highly hydrophobic triphenylporphyrin bearing different alkyl chains, were synthesized. Although differently sized, all conjugates self-assemble into similar to 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 exper-iments 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 photochemical internalization (PCI). Our approach expands the field of PCI into different small molecule chemotherapeutics.

Automated summary

In order to target cancer cell lysosomes for drug transport and light-controlled release, we synthesized new conjugates of beta-cyclodextrin with highly hydrophobic triphenylporphyrin. These conjugates self-assemble into similar nanoparticles in water and selectively target the lysosomes of breast adenocarcinoma cells. The nanoparticles exhibit photoactivity and can bind with different anticancer drugs.