Peptide-Based Nanoparticle for Tumor Therapy

Abstract

Cancer treatment continues to face significant challenges due to the limitations of conventional therapies, including non-specific toxicity, poor bioavailability, and drug resistance. Nanotechnology, particularly peptide-based nanoparticles (NPs), is increasingly recognized as a valuable strategy to address these obstacles. Peptides provide a versatile platform offering high biocompatibility, specificity, biodegradability, and minimal immunogenicity, making them ideal for targeted cancer therapies. This review comprehensively examines recent advancements in peptide-based nanoparticle systems, highlighting the mechanisms driving peptide self-assembly, such as amphiphilicity, non-covalent interactions, and metal coordination. It distinguishes between non-bioactive peptide nanoparticles, which primarily serve as drug carriers, and bioactive peptide nanoparticles, which integrate targeting peptides, cell-penetrating peptides (CPPs), and therapeutic peptides to enhance specificity, internalization, and anticancer efficacy. Emphasis is placed on innovative designs that exploit active targeting, stimuli-responsive release, and immunomodulatory strategies to maximize therapeutic outcomes while minimizing side effects. Despite promising preclinical outcomes, the clinical translation of peptide nanoparticles struggles with challenges involving stability, delivery efficiency, scalability, regulatory compliance, and manufacturing complexity. The review concludes by outlining future directions, emphasizing personalized nanomedicine, combination therapies, and advanced peptide engineering as crucial pathways toward successful clinical implementation.

Keywords: cancer therapy; nanomedicine; peptide nanoparticles; self-assembly.

Figure 1

Overview of peptide nanoparticle strategies for cancer therapy. (A) Nanoparticle core (e.g., polymer, lipid) with targeting peptides conjugated to the surface. (B) Nanoparticle core with cell-penetrating peptides (CPPs) conjugated to the surface. (C) Nanoparticle encapsulating therapeutic peptides as cargo. (D) Nanostructure formed by the self-assembly of peptides (e.g., micelles, nanofibers) encapsulating a drug. (E) Multifunctional nanoparticle combining several elements (e.g., targeting peptide + CPP + drug payload).

Figure 2

Driving forces and control of peptide self-assembly. The key non-covalent interactions, (A) hydrogen bonding, (B) electrostatic interactions, (C) van der Waals forces, (D) hydrophobic interactions, and (E) π–π stacking, drive peptide self-assembly. It could also visually represent how factors like pH, temperature, or peptide sequence modification can influence the resulting nanostructure morphology (e.g., micelles vs. nanofibers vs. vesicles).

Figure 3

Examples of non-bioactive peptide nanoparticle architectures. (A) Polypeptide nanoparticle formulated from longer chains of amino acids. (B) Peptide dendrimer nanoparticles formulated from branched polypeptides. (C) Elastin-like polypeptides (ELPs) system.

Figure 4

Mechanisms of action for bioactive peptide nanoparticles. (A) Targeting peptides bind to receptors. (B) CPPs facilitate entry across the cell membrane. (C) Therapeutic peptides trigger tumor cell death.

Figure 5

Peptide nanoparticles in cancer immunotherapy. Nanoparticle delivering peptide antigens +/− adjuvants to an antigen-presenting cell (APC) leading to T cell activation. Nanoparticle delivering peptides that block PD-1/PD-L1 or other checkpoint interactions between T cells and tumor cells. Nanoparticles targeting and modulating immunosuppressive cells (e.g., M2 TAMs) or delivering cytokines within the TME.