Mesoporous polydopamine with built-in plasmonic core: Traceable and NIR triggered delivery of functional proteins

Functional proteins are essential for the regulation of cellular behaviors and have found growing therapeutic uses. However, low bioavailability of active proteins to their intracellular targets has been a long-standing challenge to achieve their full potential for cell reprogramming and disease treatment. Here we report mesoporous polydopamine (mPDA) with a built-in plasmonic nanoparticle core as a multifunctional protein delivery system. The mPDA with a unique combination of large surface area, metal-chelating property, and broad-spectrum photothermal transduction allows efficient loading and near-infrared light-triggered release of functional proteins, while the plasmonic core serves as a photostable tracer and fluorescence quencher, collectively leading to real-time monitoring and active cytosolic release of model proteins. In particular, controlled delivery of cytotoxic ribonuclease A has shown excellent performance in invivo cancer therapy. The possibility of coating mPDA on a broad range of functional cores, thanks to its universal adhesion, provides opportunities for developing tailored delivery carriers of biologics to overcome intrinsic biological barriers. Ministry of Education (MOE) This work was supported by the National Natural Science Foundation of China (No. 21473157 and No. 81872807), Fundamental Research Funds for the Central Universities (2018XZZX001-14) and the Ministry of Education-Singapore (MOE2015-T2-1-112 and MOE2013- T3-1-002). D. Wu thanks the China Scholarship Council (No. 201706320290) for financial support to visit Nanyang Technological University, Singapore. Green fluorescent protein was produced with the assistance of Dr. Kanagavel Deepankumar. D. Wu and J. Zhou contributed equally to this work.