Peptides in biomedicine: Harnessing nanotechnology

Nanotechnology offers several advantages and opportunities to enhance peptide applications in biomedicine.
1. Improved Drug Delivery: Nanotechnology provides efficient strategies for delivering peptides to their target sites in the body. Nanoparticles can encapsulate or conjugate peptides, protecting them from degradation and enhancing their stability. These nanocarriers can improve peptide solubility, prolong circulation time, and facilitate controlled release, leading to enhanced drug delivery and improved therapeutic outcomes. For example, the recently published article by Diaz-Villares et al 2023 demonstrates a significantly increase in the retention time of a senolytic peptide for the treatment of osteoarthritis after intra-articular injection, when the peptide was loaded into biodegradable nanosystems, in relation to the free peptide (3).
2. Enhanced Peptide Stability: Peptides are susceptible to enzymatic degradation, limiting their therapeutic potential. Nanotechnology can address this challenge by protecting peptides from degradation. Encapsulation of peptides within nanoparticles or coating them with biocompatible materials provides a protective shield, preserving their structure and bioactivity during storage and delivery.
3. Targeted Delivery: Nanoparticles can be engineered to selectively target specific cells, tissues, or organs, enhancing the specificity of peptide delivery. Functionalization of nanoparticles with targeting ligands, such as antibodies or peptides, allows for site-specific accumulation and cellular internalization of the peptide cargo. This targeted delivery approach reduces off-target effects and improves the efficacy of peptide therapeutics.
4. Combination Therapies: Nanotechnology enables the development of combination therapies by co-delivering peptides and other therapeutic agents. Nanoparticles can carry multiple payloads, such as peptides, chemotherapy drugs, or imaging agents, within a single system. This approach allows for synergistic effects, simultaneous diagnosis and treatment, and personalized medicine approaches.
5. Imaging and Diagnostics: Nanotechnology-based platforms can be utilized for peptide-based imaging and diagnostic applications. Nanoparticles can be engineered to carry peptide probes that specifically bind to disease-associated biomarkers. By incorporating imaging agents onto nanoparticles, such as quantum dots or iron oxide nanoparticles, targeted imaging of specific tissues or disease sites can be achieved.
6. Controlled Release Systems: Nanotechnology offers controlled release systems for peptide delivery. Nanoparticles can be designed to respond to specific stimuli, such as pH, temperature, or enzymes, to trigger the release of encapsulated peptides. This approach allows for site-specific, on-demand release of peptides, optimizing therapeutic efficacy and reducing side effects.

Over the years, significant research efforts have been focused on developing novel delivery systems to overcome these limitations (nanoparticles, microneedles, and peptide conjugates). Nanoparticles have gained significant attention as carriers for peptide delivery due to their unique properties, including high surface area, tunable size, and surface modifications, which will lead to a reduction in the drug side effects and an increase in the drug’s efficacy. Among these, lipidic nanoemulsions, emerged as a promising strategy for enhancing peptide delivery.

The association efficiency is crucial for ensuring optimal loading and stability of peptides within the delivery system, which directly impacts their release kinetics and targeted delivery to the desired site.
DIVERSA technology can associate a wide variety of therapeutic peptides with different length, peptide charge, hydrophobicity, and isoelectric point, showing great association efficiencies between 70-99% (table 1) and maintaining the nanometric size below 300 nm (Fig. 2).

The efficient internalization of peptides into target cells is crucial for achieving their desired therapeutic effects or facilitating specific cellular processes.

DIVERSA Peptide Delivery Reagent can efficiently enhance cellular uptake, promote endosomal escape, enable targeted delivery, protect peptides from degradation, and facilitate intracellular release, not only in vitro, but also in vivo (Figure 3, 5).