Small anticancer drug release by light: Photochemical internalization of porphyrin-β-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 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 photochemical internalization (PCI). Our approach expands the field of PCI into different small molecule chemotherapeutics. [Display omitted] •New, neutral, amphiphilic βCD-triphenylporphyrin conjugates were synthesized.•Although different, they all form very similarly sized nanoparticles (NPs).•The NPs specifically target and accumulate in the lysosomes of MCF-7 cells.•The non-toxic NPs transport differently structured anticancer drugs to lysosomes.•Red light irradiation causes drug release conferring major and lasting toxicity to cells.