Non-covalent peptide anchoring strategies enhance liposomal nanocarrier functionalization for targeted cancer therapy

Conventional cancer treatments face challenges like off-target toxicity, poor bioavailability, and therapeutic resistance, limiting success in diseases like breast cancer. Targeted drug delivery systems, particularly liposomes, offer a promising solution by improving drug effectiveness and precision. Traditional liposomal functionalization relies on covalent bonding of targeting ligands, which can be complex and potentially compromise ligand activity. This creates a critical gap for simpler, more adaptable methods to integrate targeting peptides.

This comprehensive review systematically examined non-covalent peptide-liposome interactions as a primary focus for functionalizing liposomal nanocarriers. Researchers analyzed various mechanisms of peptide incorporation, including hydrophobic interactions and electrostatic forces, alongside specific incorporation techniques. The review also evaluated therapeutic applications, emphasizing formulation-relevant criteria such as stability, manufacturability, and clinical translation. It provided critical evaluation of comparative advantages and limitations of each strategy, addressing manufacturing challenges, quality control, and regulatory considerations.

Non-covalent peptide insertion offers a significantly simpler and more adaptable approach for incorporating targeting peptides into liposomal membranes compared to traditional covalent methods. Key mechanisms driving this integration include hydrophobic interactions and electrostatic forces, allowing for modular design. The review identified that these strategies can enhance the precision and effectiveness of targeted cancer therapies by maintaining ligand activity and simplifying the functionalization process. It detailed how these methods facilitate the development of more versatile drug carriers, improving drug delivery to tumor sites while minimizing systemic toxicity. Critical decision frameworks were provided for formulation scientists, guiding the selection of optimal non-covalent strategies based on specific therapeutic goals and manufacturing feasibility. > The review underscores that non-covalent peptide anchoring strategies present a robust pathway to overcome complexities associated with covalent functionalization, paving the way for advanced targeted nanomedicines.