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Funded Project (2022-2024)Combining Single-step Layer-by-Layer Electrostatic Assembly and Two-Photon Laser Printing for Hierarchical Functional Microsystems with Controllable Drug Release

In nature, during the evolution of cells, some nucleic acids and a large number of proteins can spontaneously assemble with each other, spontaneously forming a uniform and stable core-satellite superstructure of protein shell wrapped around nucleic acids. Artificial building blocks such as ions, molecules, polymers, nanoparticles, microparticles and macroscopic substrates have become important candidates for assembling functional superstructures in drug delivery, nanosensors and other fields. Like the spontaneous assembly of natural cell structures, the spontaneous assembly of core-satellite superstructures with long-range order from simple artificial building blocks is of great interest for bio-nano interaction materials. These assembled artificial core-satellite superstructures exhibit nanoscale resolution and controllable morphologies, contributing to enhanced synergistic properties for drug delivery, photonics, chemical sensing, energy storage and catalysis, etc. As controlled release systems, the release rate generally depends on the thickness of the nanoshells of the material used. Thicker shells result in longer release times.  

In the design of controlled release systems for drugs, food and cosmetics, 3D printing technology, with its unique ability to produce complex and diverse shapes, opens new doors for the design of novel controlled release systems. The combination of spontaneous assembly of artificial building blocks and two-photon laser printing (2PLP) will be extended to construct multilayer nanoshells on complex 3D printed hollow microcages. 2PLP allows the design of hollow microcage architectures as cores with higher drug loading capacity as well as specific unloading sites, and the design of controllable multilayer nanoshells on hollow microcages helps to enhance and modulate effects for biomedical applications for in vivo drug delivery.

In this research, we aim to develop a new assembly strategy that can spontaneously assemble artificial building blocks directly from one-pot dispersions and guide them to assemble on printed 3D microstructured cores. Our new assembly method will easily adjust parameters such as the number of layers of nanocoated shells and the core diameter. Based on the previously reported core geometry, the superstructures are limited to spherical shapes, which may not be the optimal geometry for controlled release systems with high loading capacity. To overcome this limitation, we will use 2PLP printing as powerful tool to develop more diverse hollow 3D microstructures as the core of superstructures. The combination of spontaneous assembly and 2PLP will design multi-scale hollow superstructures with high drug loading capacity for in vivo disease treatment.

Schematic representation of 2PLP printing as tool to develop more diverse hollow 3D microstructures as the core of superstructures