Self-assembled non-covalent protein-drug nanoparticles: an emerging delivery platform for anti-cancer drugs

Introduction Protein nanocarriers offer advantageous delivery platforms for anti-cancer drugs, provided by their biocompatibility, high drug loading capacity, and their ability to encapsulate hydrophobic active therapeutics. However, the conventional fabrication techniques of protein nanoparticles (NPs) often suffer from incorporation of considerable amounts of toxic solvents and crosslinking agents which may result in significant toxicity or compromise the drug stability. Therefore, novel strategies were proposed to induce non-covalent self-assembly of proteins by exploiting hydrophobic interactions or manipulation of disulfide bonds to produce nontoxic crosslinker-free drug-loaded protein NPs. Thermal mediated unfolding, the use of reducing agents, modulation of pH and ionic strength, chemical-induced denaturation as well as photochemical methods can be efficiently utilized to induce the protein self-assembly process. Areas covered In this review, we highlight the novel approaches used in the development of non-covalent protein-drug nano-assemblies, formulation factors, their implications, limitations, and treatment outcomes as well as future challenges. Expert opinion Formulation of protein-drug nanocarriers via non-covalent self-assembly can be advantageous as a promising strategy for efficient and safe tumor-targeted delivery of anti-cancer drugs compared to the conventional nano-fabrication technologies.