Hepatoma Metastasis‐Inhibiting Supramolecular Nanoglycocalyx for Enhanced Type I Photodynamic Therapy
Yichen Liu, Gai‐li Feng, Jialong Jie, Wei Zhou, Guang‐jian Liu, Yuan Zhang, Hongmei Su, Guo‐wen Xing
Abstract
Abstract Type I photodynamic therapy (PDT) is well demonstrated to have low oxygen dependency. However, fully suppressing the risk of hypoxia‐induced tumor metastasis during PDT remains a great challenge. In this study, a tetra‐lactosylated amphiphilic Aza‐BODIPY glycocluster ( TLBP ) is reported that self‐assembles into a supramolecular nanoglycocalyx on hepatoma cell membranes, serving as an artificial extracellular matrix (ECM) to inhibit hepatoma metastasis while facilitating efficient Type I PDT. Molecular engineering demonstrates that multi‐glycosylation promotes the transition of nanostructures from disordered to ordered self‐assembly by regulating intermolecular interactions. This modification enables the TLBP glycocalyx to exhibit significant intermolecular electron transfer, generating superoxide anion radicals (O 2 −• ) for Type I PDT. Moreover, the TLBP glycocalyx inhibits the PI3K‐Akt signaling pathway by reducing Na + /K + ‐ATPase activity, leading to decreased migration and invasion of HepG2 cells. The synergistic antitumor effect of TLBP glycocalyx is further verified in a HepG2‐bearing mouse model. This work innovatively utilizes glycosylation to regulate microelectronic properties and macroscopic nanoscale self‐assembly characteristics, providing a novel concept for developing efficient synergistic anti‐hepatoma strategies.