Folic Acid-Modified Cyclodextrin Multivalent Supramolecular Assembly for Photodynamic Therapy.

The construction of supramolecular multivalent assemblies with unique photoluminescence behaviors and biological functions has become a research hot spot recently in the biomaterial field. Herein, we report an adaptive supramolecular assembly via a multivalent co-assembly strategy prepared in two stages by using an adamantane-connected pyrenyl pyridinium derivative (APA2), sulfonated aluminum phthalocyanine (PcS), and folic acid-modified β-cyclodextrin (FA-CD) for efficient dual-organelle targeted photodynamic cancer cell ablation. Benefiting from π-π and electrostatic interactions, APA2 and PcS could first assemble into non-fluorescent irregular nanoaggregates because of the heterodimer aggregation-induced quenching and then secondarily assemble with FA-CD to afford targeted spherical nanoparticles (NPs) with an average diameter of around 50 nm, which could be specifically taken up by HeLa cancer cells through endocytosis in comparison with 293T normal cells. Intriguingly, such multivalent NPs could adaptively disaggregate in an intracellular physiological environment of cancer cells and further respectively and selectively accumulate in mitochondria and lysosomes, which not only displayed near-infrared two-organelle localization in situ but also aroused efficient singlet oxygen generation under light irradiation to effectively eliminate cancer cells up to 99%. This supramolecular multivalent assembly with an adaptive feature in a specific cancer cell environment provides a feasible strategy for precise organelle-targeted imaging and an efficiently synergetic photodynamic effect in situ for cancer cell ablation.