Exploring Linker-Group-Guided Self-Assembly of Ultrathin 2D Supramolecular Nanosheets in Water for Synergistic Cancer Phototherapy

Water is ubiquitous in natural systems where it builds an essential environment supporting biological supramolecular polymers to function, transport, and exchange. However, this extreme polar environment becomes a hindrance for the superhydrophobic functional π-conjugated molecules, causing significant negative impacts on regulating their aggregation pathways, structures, and properties of the subsequently assembled nanomaterials. It especially makes the self-assembly of ultrathin two-dimensional (2D) functional nanomaterials by π-conjugated molecules a grand challenge in water, although ultrathin 2D functional nanomaterials have exhibited unique and superior properties. Herein, we demonstrate the organic solvent-free self-assembly of one-molecule-thick 2D nanosheets based on exploring how side chain modifications rule the aggregation behaviors of π-conjugated macrocycles in water. Through an in-depth understanding of the roles of linking groups for side chains on affecting the aggregation behaviors of porphyrins in water, the regulation of molecular arrangement in the aggregated state (H- or J-type aggregation) was attained. Moreover, by arranging ionic porphyrins into 2D single layers through J-aggregation, the ultrathin nanosheets (thickness ≈ 2 nm) with excellent solubility and stability were self-assembled in pure water, which demonstrated both outstanding 1O2 generation and photothermal capability. The ultrathin nanosheets were further investigated as metal- and carrier-free nanodrugs for synergetic phototherapies of cancers both in vitro and in vivo, which are highly desirable by combining the advantages and avoiding the disadvantages of the single use of PDT or PTT.