A Nano‐in‐Nano Vector: Merging the Best of Polymeric Nanoparticles and Drug Nanocrystals

An advanced approach that can prepare narrowly size distributed nanomaterials with ultrahigh mass fraction of therapeutics, superior colloidal stability, minimal off‐target effects, as well as precisely controlled drug‐release profiles, is strongly desirable. Here, an optimal nano‐in‐nano vector, consisting of a drug (sorafenib, SFN, or itraconazole, ICZ) nanocrystal core and a polymer (folic acid conjugated spermine‐functionalized acetalated dextran, ADS‐FA) shell on a 1:1 ratio (HSFN@ADS‐FA or ICZ@ADS‐FA) is successfully fabricated. With the help of computational fluid dynamics, the concentration and velocity field are computed in the microfluidic domain, as well as the mixing time between the solvent and nonsolvent for nanovector precursors. The favorable features of both polymer nanoparticles and drug nanocrystals are inherited by the obtained nano‐in‐nano vector, showing ultrahigh drug‐loading degree, biodegradability, pH‐responsive fast dissolution, high stability in serum, and ease of surface functionalization. Furthermore, the half‐maximal inhibitory concentration value of the nano‐in‐nano HSFN@ADS‐FA is ≈54 times lower than the conventional nanovector (LSFN@ADS‐FA) with a low drug‐loading degree. Overall, this nano‐in‐nano vector merges the best of polymeric nanoparticles and drug nanocrystals.