Self-assembly of morphology-tunable architectures from tetraarylmethane derivatives for targeted drug delivery.

Tetraarylmethane compounds consisting of two pyrogallol and two aniline units, namely, Ar2CAr'2 {Ar = 3,4,5-C6H2(OH)3 and Ar' = 3,5-R2-4-C6H2NH2 [R = Me (1), iPr (2)]} exhibit excellent self-assembly behavior. Compound 1 yields size-tunable hollow nanospheres (HNSs) with a narrow size distribution, and 2 yields various morphologies ranging from microtubules to microrods via self-assembly induced by hydrogen bonding and π-π stacking interactions. On the basis of the experimental results, a plausible mechanism for morphology tunability was proposed. As a means of utilizing the self-assembled HNSs for targeting controlled drug delivery, folic acid (FA) and rhodamine 6G (Rh6G) were grafted onto compound 1 to yield the FA-Rh6G-1 complex. The HNSs fabricated with FA-Rh6G-1 showed low cytotoxicity against human embryonic kidney 293T cells and CT26 colon carcinoma cells and good doxorubicin (DOX) loading capacity (9.6 wt %). The FA receptor-mediated endocytosis of FA-Rh6G-1 HNSs examined by using a confocal laser scanning microscope and a flow cytometer revealed that the uptake of FA-Rh6G-1 HNSs into CT26 cells was induced by FA receptor-mediated endocytosis. In vitro drug delivery tests showed that the DOX molecules were released from the resulting HNSs in a sustainable and pH-dependent manner, demonstrating a potential application for HNSs in targeted drug delivery for cancer therapy.