Peptide-Based Inorganic Nanoparticles as Efficient Intracellular Delivery Systems

Background/Objectives: Peptide-based inorganic nanoparticles (PINPs) have emerged as promising candidates for intracellular delivery due to their unique structural and functional attributes. These hybrid nanostructures combine the high surface area and tunable optical/magnetic properties of metal cores (e.g., Au, Ag, Fe₃O₄) with the biocompatibility, targeting specificity, and responsive behavior of peptides. In particular, peptides with amphipathic or cell-penetrating features could facilitate efficient transport of molecular cargos across cellular membranes while enabling stimulus-responsive drug release in target tissues. Methods: We review key synthesis methods (especially green, peptide-mediated one-pot approaches), functionalization strategies (e.g., thiol-gold bonds, click chemistries), and characterization techniques (TEM, DLS, FTIR, etc.) that underpin PINP design. In addition, we highlight diverse peptide classes (linear, cyclic, amphipathic, self-assembling) and their roles (targeting ligands, capping/stabilizing agents, reducing agents) in constructing multifunctional nanocarriers. Results: The prospects of PINPs are considerable: they enable targeted drug delivery with imaging/theranostic capability, improve drug stability and cellular uptake, and harness peptide programmability for precision nanomedicine. However, challenges such as in vivo stability, immunogenicity, and standardization of evaluation must be addressed. Conclusions: Overall, PINPs represent multifunctional platforms that could significantly advance drug delivery and diagnostic applications in the future.