Fatty-Amine-Conjugated Cationic Bovine Serum Albumin Nanoparticles for Target-Specific Hydrophobic Drug Delivery

Protein-based nanostructures have reformed nanoscience and nanotechnology on account of their smaller sizes and greater surface areas, which instigate their interactions with other molecules. The protein nanoparticles (NPs) have good biocompatibility, biodegradability, and easy access for additional surface modifications. These NPs have been successfully used as drug delivery systems with increased bioavailability and reduced toxic side effects of the drug molecules. Herein, we report a simple approach to formulating fatty-amine-conjugated cationic BSA (FCBSA) NPs by conjugating laurylamines to the BSA protein. Partial neutralization of the negatively charged glutamic acid or aspartic acid residues by the formation of an amide bond with laurylamines leads to the formation of cationic NPs under physiological conditions (isoelectric point = 7.7 and zeta potential = +7 mV at pH 7.2). The NPs exhibit high stability against thermal, pH, and proteolytic enzyme stresses. The NPs demonstrated excellent biocompatibility against both normal and cancer cell lines. The protein NPs efficiently encapsulate hydrophobic anticancer drug doxorubicin (Dox) and have a controlled release property (∼40% release after 3 days), human blood serum stability, antifouling properties, and a higher binding affinity for the anionic membranes. The biotin tagged cationic FCBSA (bt-FCBSA) also showed very similar biophysical properties to those of FCBSA. Furthermore, the cellular studies also showed that bt-FCBSA can efficiently deliver Dox to the biotin receptor-positive HeLa cells, leading to significant cell death. An in vivo assessment of the Dox-encapsulated bt-FCBSA on Ehrlich ascites carcinoma cells on female Swiss albino mice revealed a significant inhibition of tumor growth. Overall, easy access to the fatty-amine-modified cationic protein NPs with their surface modification capabilities could qualify them as candidates for both passive and active targeted delivery of anticancer agents.