Polyethyleneimine coated cellulose nanocrystals decorated with 3-carboxyphenylboronic acid as a pH-responsive nanocarrier for targeted drug delivery

In recent years, cellulose nanocrystals (CNCs) have been used to deliver drugs, showing great potential in exploring new methods for cancer chemotherapy. Nevertheless, insolubility, low stability, and bioavailability of the potential bioactive compounds obstruct the development of bioactive formulations. Here, we constructed a pH-responsive nanocarrier that can actively target hepatocellular carcinoma cells (HCC) to deliver insoluble drug curcumin (Cur). Firstly, the polyethyleneimine (PEI) was coated onto the surface of CNCs (CNCs@PEI), and then the 3-carboxyphenylboronic acid (BA) was grafted with the coated PEI (CNCs@PEI-BA). After that, Cur formed a borate structure with BA to load Cur (CNCs@PEI-BA-Cur) showed a high drug loading capacity of 15.74%. CNCs@PEI-BA-Cur actively target HCC, enter into lysosomes, and release Cur in response to the low pH value environment. Importantly, CNCs@PEI-BA-Cur released 10.7-folds of Cur in acidic environments (pH = 5.4) more than in neutral environments (pH = 7.2). Furthermore, the nanocarrier showed efficient active targeting of HCC and increased intracellular Cur concentrations, which allowed for the effective killing of HCC in 2D cell and 3D hepatoma cell microsphere models in vitro. In conclusion, this targeted and pH-responsive nanocarrier was expected to enhance the therapeutic of insoluble drugs for HCC.