Bioinspired strategies enhance biomacromolecule delivery by mimicking viral and cellular pathways
Background
The therapeutic potential of biomacromolecular therapeutics, such as proteins and nucleic acids, is often hampered by significant delivery challenges. These include poor stability in biological environments, inefficient cellular uptake, and inadequate intracellular trafficking to their target sites. Current delivery methods frequently fall short in achieving the necessary specificity and efficacy, particularly for hard-to-reach cells or poorly permeable tissues. Bioinspired synthetic strategies, which borrow principles or directly mimic biological mechanisms, are emerging as a crucial approach to surmount these fundamental barriers and unlock the full therapeutic promise of these advanced drugs.
Study Design
This review systematically examined lipid- and polymer-based systems designed for protein and nucleic acid delivery, drawing from two primary paradigms: virus-mimicking systems and peptide/protein pathway-based mimicry. Literature was identified through comprehensive searches across PubMed, Nature, Scopus, and Web of Science, specifically focusing on innovations from the last 15 years. Unlike reviews centered on membrane-coated carriers or single modalities, this work used the cell-membrane interaction as a unifying principle to organize and analyze diverse delivery strategies for both protein and nucleic acid cargo types.
Results
The review categorized virus-mimicking platforms into two main groups: structural mimicry and functional mimicry. Structural mimicry encompasses systems like capsid-like nanoparticles, fusogenic liposomes, and dendrimers, which physically resemble viral structures. Functional mimicry includes pH-responsive endosomolytic and environmentally triggered systems that replicate viral entry mechanisms. Pathway-based approaches were shown to leverage natural biological processes, spanning strategies such as receptor-mediated blood-brain barrier transport, fibrinogen bridging for thrombus targeting, and charge-mediated membrane penetration for enhanced cellular uptake. The unifying principle across all these diverse strategies is their optimized interaction with the cell membrane, facilitating improved cargo delivery.
The review highlights how these bioinspired systems collectively provide robust strategies to surmount physiological and pathological barriers in biomacromolecule delivery.
Key Findings
- Biomacromolecular therapeutics face significant challenges in stability, cellular uptake, and intracellular trafficking.
- Bioinspired synthetic strategies, including virus-mimicking and pathway-based approaches, address these delivery barriers.
- Virus-mimicking systems employ structural (e.g., capsid-like nanoparticles) and functional (e.g., pH-responsive) mimicry.
- Pathway-based approaches leverage natural mechanisms like receptor-mediated transport and charge-mediated penetration.
- Computational design, machine learning, and multifunctional nanoparticles are poised to accelerate future precision delivery.
Why It Matters
This comprehensive review underscores the critical role of bioinspired design in advancing the field of drug delivery for complex biomacromolecules. Future therapeutic protocols will likely integrate computational design and machine-learning-guided optimization to accelerate the translation of these sophisticated delivery systems. The emergence of hybrid lipid-polymer architectures is expected to offer enhanced stability and versatility. Moreover, the next generation of precision biomacromolecule delivery systems will likely be defined by stimuli-responsive, multifunctional nanoparticles that seamlessly integrate targeting, controlled release, and diagnostic capabilities, paving the way for highly effective and personalized treatments.
drug-delivery
biomacromolecules
nanoparticles
liposomes
polymers
cell-membrane