Application of gelatin nanoconjugates as potential internal stimuli-responsive platforms for cancer drug delivery

Nanoparticles (NPs) have been continuously utilized for different implementations, most particularly for cancer drug delivery. A large number of NP-based drug delivery systems (DDSs) have been explored for cancer therapy and a variety of materials have been investigated as potential drug delivery materials to ameliorate the therapeutic potency and harmlessness of anticancer drugs. Proteins NPs like albumin, lactoglobulin and gelatin are considered as outstanding alternatives to be formulated into the nanostructure platforms in conjugation with anticancer drugs because of their safety, biodegradability and biocompatibility. Also, their uncomplicated preparation and modification can be carried out under mild conditions with no concern toward the utilization of hazardous reagents. Therefore, in this paper we present an overview on the different methods for formulation of protein nanostructure including emulsification, simple desolvation/coacervation, complex coacervation (self-assembled), and electrospray. We then review the application of protein NPs especially gelatin NPs (GNPs) as potential candidates in DDSs which can be achieved through internal [pH, matrix metalloproteinase (MMP)] stimuli-responsive smart platforms for cancer therapy. Finally, many of the current challenges, future development of GNPs and their integration into clinical practice were discussed. This paper may pave the way to disclose some details about the healthcare transformation of GNPs toward precision medicine.