Nanotechnology approaches play an important role in developing novel and efficient carriers for biomedical applications. Peptides are particularly appealing to generate such nanocarriers because they can be rationally designed to serve as building blocks for self-assembling nanoscale structures with great potential as therapeutic or diagnostic delivery vehicles. In this review, we describe peptide-based nanoassemblies and highlight features that make them particularly attractive for the delivery of nucleic acids to host cells or improve the specificity and sensitivity of probes in diagnostic imaging. We outline the current state in the design of peptides and peptide-conjugates and the paradigms of their self-assembly into well-defined nanostructures, as well as the co-assembly of nucleic acids to form less structured nanoparticles. Various recent examples of engineered peptides and peptide-conjugates promoting self-assembly and providing the structures with wanted functionalities are presented. The advantages of peptides are not only their biocompatibility and biodegradability, but the possibility of sheer limitless combinations and modifications of amino acid residues to induce the assembly of modular, multiplexed delivery systems. Moreover, functions that nature encoded in peptides, such as their ability to target molecular recognition sites, can be emulated repeatedly in nanoassemblies. Finally, we present recent examples where self-assembled peptide-based assemblies with “smart” activity are used in vivo. Gene delivery and diagnostic imaging in mouse tumor models exemplify the great potential of peptide nanoassemblies for future clinical applications.

Concerns associated with nanocarriers’ therapeutic efficacy and side effects have led to the development of strategies to advance them into targeted and responsive delivery systems. Owing to their bioactivity and biocompatibility, peptides play a key role in these strategies and, thus, have been extensively studied in nanomedicine. Peptide-based nanocarriers, in particular, have burgeoned with advances in purely peptidic structures and in combinations of peptides, both native and modified, with polymers, lipids, and inorganic nanoparticles. In this review, we summarize advances on peptides promoting gene delivery systems. The efficacy of nucleic acid therapies largely depends on cell internalization and the delivery to subcellular organelles. Hence, the review focuses on nanocarriers where peptides are pivotal in ferrying nucleic acids to their site of action, with a special emphasis on peptides that assist anionic, water-soluble nucleic acids in crossing the membrane barriers they encounter on their way to efficient function. In a second part, we address how peptides advance nanoassembly delivery tools, such that they navigate delivery barriers and release their nucleic acid cargo at specific sites in a controlled fashion.

In this investigation, gallic acid (GA) and curcumin (Cur) were co-encapsulated into RGD-functionalized liposomes, denoted as GA-Cur-RFL. The synthesized liposomes were characterized, and their anticancer activity was assessed through MTT assays and annexin V/PI apoptosis kit assays conducted on PC-3 prostate cancer cells. Transmission electron microscopy (TEM) analysis revealed liposomes with a uniform morphology, approximately 100 nm in size. Dynamic light scattering (DLS) analysis further indicated a hydrodynamic size of 160.8 ± 2.3 for the liposomes. Cytotoxicity assays revealed that the cytotoxicity of GA exhibited concentration and time dependency. Moreover, the results underscored that Cur significantly enhanced the anticancer effect of GA. Additionally, the functionalization of liposomes with RGD peptide was found to increase the cytotoxicity of liposomes containing both compounds compared to free drugs and drugs encapsulated into simple liposomes. Apoptosis assays yielded compelling results, showcasing a notable improvement in late apoptosis (20% late apoptosis) for GA-Cur-RFL in comparison to non-functionalized nanoliposomes and the free form of compounds (13.6% and 12% late apoptosis, respectively). These findings conclusively demonstrate that the co-administration and delivery of Cur and GA substantially amplify their cytotoxic effects. Importantly, the enhanced apoptosis induction by GA-Cur-RFL in PC-3 cells can be attributed to the RGD modification, facilitating increased cellular absorption of GA and Cur. These insights advance our understanding of the mechanisms involved and hold promise for the development of more effective and targeted cancer therapies.