Controlled Growth of N-Doped and Large Mesoporous Carbon Spheres with Adjustable Litchi-Like Surface and Particle Size as a Giant Guest Molecule Carrier

N-doped mesoporous carbon nanospheres (NMCNs) with tunable particle size, pore size, surface roughness, and inner cavity are extremely important for the future development of new carriers for nanoencapsulation, high-performance giant molecule transport, and cell uptake. However, constructing such a multifunctional material via a simple method still remains a great challenge. Herein, a controlled growth technology was developed for the first time to synthesize such NMCNs based on the initial reaction temperature (IRT) and solution polarity. In this strategy, the IRT not only can adjust the micelle aggregation to obtain NMCNs with large mesopores but also can make the F127 micelle more lyophobic to prepare hollow N-doped mesoporous carbon spheres, which is a great breakthrough. Inspiringly, by varying the solution polarity to make nonuniform growth of nanoparticles, the litchi-like rough surface of NMCNs was obtained, which could significantly improve the cell uptake performance of NMCNs. The current understanding of nucleation and growth mechanism of nanospheres was further extended and realized the development of NMCNs with large mesopores and litchi-like rough surface, which provided a new and interesting fundamental principle for the synthesis of NMCNs. The mesoporous structure of NMCNs was successfully reverse-replicated by nanocasting of tetraethylorthosilicate to obtain mesoporous silica spheres (MSNs), revealing the easy transformation between NMCNs and MSNs. Insulin as a peptide drug cannot be directly administered orally. But it can be used as oral preparation after being loaded into NMCNs, which has never been reported before. Interestingly, the results of the animal experiment showed an excellent in vivo hypoglycemic activity. This finding provides a new paradigm for the fabrication of structurally well-defined NMCNs with a great promise for drug carriers.