A Complete Guide to How Peptides Are Used as Drug Delivery Tools — From Cell-Penetrating Peptides to Smart Linkers | Research

The takeaway

This comprehensive review catalogs all major categories of peptide-based drug delivery biomaterials — excipients, self-assembling structures, and linkers — along with the optimization strategies that make them work.

3 functional categories
The review organizes the entire peptide biomaterials landscape into excipients, self-assembling systems, and linkers — providing a unified framework for a fragmented field

What the researchers found

The review organizes peptide-based biomaterials into three major functional categories:

1. **Peptide excipients**: Cell-penetrating peptides (CPPs) enable intracellular delivery via direct membrane penetration or endocytosis; tight junction modulating peptides open passages between cells; peptide surfactants and stabilizers protect drug formulations.

2. **Self-assembling peptides**: These spontaneously form nanospheres, cyclic nanotubes, nanovesicles, micelles, hydrogels, and depot systems for controlled and sustained drug release.

3. **Peptide linkers**: Used in antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs), and prodrugs to achieve site-specific drug release triggered by tumor-associated enzymes or pH changes.

Optimization strategies include cyclization, stapling, D-amino acid incorporation, functional motif integration, and AI-assisted combinatorial discovery.

Why it matters

Drug delivery is often the biggest bottleneck in turning a promising therapeutic molecule into an effective medicine. Peptide-based biomaterials solve multiple delivery challenges — getting drugs inside cells, controlling release timing, targeting specific tissues, and improving stability. This review provides a unified framework for understanding the full spectrum of peptide delivery technologies, which is increasingly important as the field moves toward more complex therapeutic modalities like gene therapies, siRNA drugs, and targeted cancer conjugates that all depend on effective delivery.

The numbers in context

Covers CPPs, tight junction peptides, surfactants, nanospheres, nanotubes, nanovesicles, micelles, hydrogels, depots, ADC/PDC/prodrug linkers; optimization via cyclization, stapling, D-amino acids, AI

How the study worked

Systematic literature review collating advances across peptide excipients, self-assembling peptide systems, and peptide linkers for drug delivery. Covers sequence-based optimization strategies with examples from both marketed drugs and research-stage candidates.

Who was studied

Review article — no study population

What this study cannot tell us

As a broad review, it necessarily covers each topic at a survey level rather than providing deep mechanistic detail on any single technology. The review doesn't include original data. Specifics about clinical outcomes, safety profiles, or comparative efficacy of different delivery approaches are limited. The rapidly evolving nature of the field means some of the research-stage candidates discussed may have progressed or been abandoned since the review was compiled.

How to read the evidence

Not applicable — this is a comprehensive review article that synthesizes existing literature rather than reporting new experimental findings. Its value lies in organizing and contextualizing the field rather than providing new evidence.

When this study was published

Published in 2026, this is an up-to-date review covering the current state of peptide-based biomaterials including the latest developments in AI-assisted peptide design, making it a timely reference for the field.

The bigger picture

Peptide-based drug delivery is one of the fastest-growing areas in pharmaceutical science, driven by the explosion of biologics, gene therapies, and targeted cancer treatments that all need sophisticated delivery systems. The antibody-drug conjugate market alone is projected to exceed $30 billion by 2030, and peptide linkers are central to their design. Meanwhile, AI is beginning to transform how peptide sequences are optimized — a theme this review highlights as the next frontier. This comprehensive mapping of the field comes at a pivotal moment as many peptide delivery technologies transition from research to clinical application.

Questions still open

Which peptide-based delivery technology is closest to solving the oral delivery problem for large biologic drugs?
How much will AI-driven peptide design accelerate the development of optimized delivery peptides compared to traditional rational design?
Can peptide-based delivery systems overcome the endosomal escape problem that limits most intracellular delivery strategies?

Common questions

What are cell-penetrating peptides and why are they important?

Cell-penetrating peptides (CPPs) are short peptide sequences that can carry drugs, genes, or other therapeutic molecules through cell membranes into the interior of cells. This is critical because many drug targets (like cancer-driving proteins) are located inside cells, and most drugs can't get past the cell membrane on their own.

How do peptide linkers work in cancer-targeting drug conjugates?

Peptide linkers connect a targeting molecule (like an antibody) to a toxic drug payload. They're designed to stay stable in the bloodstream but break apart when they encounter conditions specific to tumors — like certain enzymes or acidic pH. This releases the drug precisely at the tumor, minimizing damage to healthy tissue.

Read the original research

Functional Peptide-Based Biomaterials for Pharmaceutical Application: Sequences, Mechanisms, and Optimization Strategies.

Journal of functional biomaterials, 17(1)

View on PubMed ↗Publisher’s paper ↗

Citation

Yu, Dedong; Han, Nari; Son, Hyejeong; Kim, Sun Jo; Kweon, Seho. (2026). Functional Peptide-Based Biomaterials for Pharmaceutical Application: Sequences, Mechanisms, and Optimization Strategies.. Journal of functional biomaterials, 17(1). https://doi.org/10.3390/jfb17010037