Multicomponent synergistic immobilization via in-situ and dynamic exchange strategies for constructing hierarchical biopharmaceuticals

Hierarchical immobilization of multicomponent biomacromolecules has been demonstrated to be a favorable protocol for constructing advanced biopharmaceuticals, but still with formidable challenges. Herein, we innovate a multicomponent synergistic immobilization approach combining an in-situ method with a structural-transformation-promoted dynamic exchange method in a flexible zeolitic pyrimidine framework (ZPF) platform to construct multicomponent biopharmaceuticals. In-depth mechanism investigation reveals that special functional groups (e.g., carboxyl, sulfhydryl, imidazolyl) on protein surface can significantly promote the dynamic structural transformation of ZPF and allow for the efficient immobilization of proteins on the surface of ZPF crystals via dynamic exchange approach. By combining with the in-situ method, which can immobilize biomacromolecules in the inner part of ZPF crystals, multicomponent biomacromolecules can be regionally localized within ZPF crystals. This controlled spatial preparation provides substantial advantages over conventional core-shell architectures for cascading enzyme immobilization and enables the development of advanced anticancer agents demonstrating enhanced therapeutic efficacy for female Balb/c nu mice. Moreover, this platform can also generate highly efficient hierarchical antibacterial formulations to significantly enhance the wound-healing process of male Sprague-Dawley (SD) rats. This study provides a revolution to immobilize multicomponent biomacromolecules and represents an innovative and effective platform of biopharmaceuticals with immense potential for anticancer and antibacterial formulations.