Self-Assembled 2D Glycoclusters for the Targeted Delivery of Theranostic Agents to Triple-Negative Breast Cancer Cells

Triple-negative breast cancer (TNBC) is a devastating disease worldwide, for which targeted imaging and therapeutic agents remain elusive. There has been growing awareness that carbohydrates are valuable as drug candidates and targeting agents for a variety of human diseases, including cancers that overexpress carbohydrate receptors on the cell surface. Here, we develop a two-dimensional (2D) glycocluster by means of simple, stepwise self-assembly for the targeted delivery of theranostic agents to TNBC cells that express mannose receptors (MRs) on the cell surface. Human serum albumin, which contains a variety of hydrophobic pockets capable of accommodating small molecules, was used to simultaneously encapsulate a mannose-based glycoprobe and a commercial photosensitizer (i.e., Ce6). The multicomponent "neoglycoprotein" formed was used to self-assemble with 2D MnO₂, producing 2D glycoclusters, which could be selectively internalized by a TNBC cell line (MDA-MB-231) as facilitated by binding to the transmembrane MR. The intracellular degradation of the 2D MnO₂ backbone by biothiols then released Ce6 for cell imaging and, subsequently, photodynamic therapy. This study provides insights into the development of carbohydrate-based materials for targeted, stimuli-responsive theranostics of TNBC.