This invention introduces a one-step self-assembly method that integrates HER2-targeted chimeric nanobodies directly into liposomal membranes, enabling scalable production of immunoliposomes with high drug encapsulation, improved tumor targeting, and reduced manufacturing complexity.
HER2-targeted therapies have shown promise for treating breast, ovarian, and gastric cancers, but conventional immunoliposome approaches rely on chemical conjugation steps that reduce ligand activity, limit drug loading, and complicate large-scale production. These inefficiencies hinder the reliability and scalability of targeted nanomedicines, slowing their translation from lab to clinic. A more streamlined and effective liposome engineering method is required to combine precision targeting, high drug loading, and cost-effective manufacturability.
This invention leverages a self-assembly strategy where engineered chimeric nanobodies (cNBs)—comprising a HER2-binding domain, flexible linker, and hydrophobic transmembrane domain or lipid tails—spontaneously insert into liposomal membranes during formation. The resulting ~100 nm liposomes encapsulate therapeutic agents with ~64% efficiency and achieve up to 95% nanobody anchoring. The nanobody-decorated liposomes show enhanced membrane stability, reduced leakage, and 10–20× greater cytotoxicity against HER2-positive cancer cells. The process eliminates post-synthesis chemical conjugation, preserves nanobody activity, and integrates seamlessly into industrial liposome manufacturing workflows.
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• One-step self-assembly removes need for chemical conjugation
• Up to 95% nanobody anchoring efficiency—significantly higher than traditional methods
• ~64% drug encapsulation efficiency using simple mixing
• Increased membrane rigidity and stability, minimizing leakage
• 10–20× improved cytotoxicity against HER2-overexpressing cells
• Compatible with existing large-scale liposome production processes
• Maintains full nanobody functionality, avoiding degradation from harsh chemistries
• Cost-effective bacterial nanobody production (>98% purity)
• Adaptable to multiple therapeutic payloads, including drugs and nucleic acids
• Large-scale HER2-targeted immunoliposome production for cancer therapy
• HER2-targeted imaging agents for diagnostics and theranostics
• Targeted chemotherapy delivery for HER2-positive breast, ovarian, and gastric cancers
• PEG-free lipid nanoparticles for HER2-targeted delivery of siRNA or mRNA
• Multifunctional nanocarriers combining therapy and imaging for precision oncology
• Expandable platform adaptable to other tumor biomarkers beyond HER2
• US Provisional Patent Application 63/552,527 – Filed February 12, 2024
• US Utility Patent Application 19/052,232 – Filed February 12, 2025
Prototype – In vitro and in vivo proof-of-concept demonstrated with validated HER2 targeting, efficient drug encapsulation, and strong cytotoxicity against cancer cells. TRL ~4–5.
This technology is available for licensing.
This invention is a strong candidate for licensing to pharmaceutical and biotech companies developing next-generation cancer nanomedicines, drug delivery platforms, and immunoliposome manufacturing technologies.
In vitro and in vivo performance data, liposome stability studies, and nanobody production details available upon request.