Programmable Biopolymers for Advancing Biomedical Applications of Fluorescent Nanodiamonds

A versatile biopolymer platform for advancing nanodiamonds (NDs) as unique magnetooptic materials for biomedical applications is presented here. Precision biopolymer coatings are designed by chemical reprogramming the functionalities of serum albumin via a straightforward synthesis protocol. Such biopolymers offer high biocompatibility and precise modification with various functional entities due to the large number of available reactive amino acid residues. Premodification of these biopolymers provides a convenient approach to customized surface functionalization of NDs. As an example, the anticancer drug doxorubicin (DOX) is conjugated to the biopolymer with high reproducibility and full characterization. The biopolymer‐coated NDs reveal excellent colloidal stabilities in all physiological media tested, even after loading with high numbers of hydrophobic DOX. The intracellular distribution of NDs and DOX is analyzed in living cells by recording the fluorescence spectra in different cellular compartments, which proves efficient intracellular release of DOX from the carrier. Studies in vitro as well as in a chick tumor xenograft model reveal efficient antitumor effects. The facile and versatile biopolymer coating strategy reported herein will greatly accelerate the availability of customized NDs with reliable and reproducible features to exploit their great potential in single molecular bioimaging, in vivo biosensing, and high resolution quantum optics.     

Polydopamine Encapsulation of Fluorescent Nanodiamonds for Biomedical Applications

Fluorescent nanodiamonds (FNDs) are promising bioimaging probes compared with other fluorescent nanomaterials such as quantum dots, dye‐doped nanoparticles, and metallic nanoclusters, due to their remarkable optical properties and excellent biocompatibility. Nevertheless, they are prone to aggregation in physiological salt solutions, and modifying their surface to conjugate biologically active agents remains challenging. Here, inspired by the adhesive protein of marine mussels, encapsulation of FNDs within a polydopamine (PDA) shell is demonstrated. These PDA surfaces are readily modified via Michael addition or Schiff base reactions with molecules presenting thiol or nitrogen derivatives. Modification of PDA shells by thiol terminated poly(ethylene glycol) (PEG‐SH) molecules to enhance colloidal stability and biocompatibility of FNDs is described. Their use as fluorescent probes for cell imaging is demonstrated; it is found that PEGylated FNDs are taken up by HeLa cells and mouse bone marrow‐derived dendritic cells and exhibit reduced nonspecific membrane adhesion. Furthermore, functionalization with biotin‐PEG‐SH is demonstrated and long‐term high‐resolution single‐molecule fluorescence based tracking measurements of FNDs tethered via streptavidin to individual biotinylated DNA molecules are performed. This robust polydopamine encapsulation and functionalization strategy presents a facile route to develop FNDs as multifunctional labels, drug delivery vehicles, and targeting agents for biomedical applications.