Peptide Amphiphiles Hitchhike on Endogenous Biomolecules for Enhanced Cancer Imaging and Therapy
The interactions of nanomaterials with biomolecules in vivo determine their biological fate. Here, it is shown that self-assembled peptide amphiphile (PA) nanostructures can dynamically interact with endogenous biomolecules and take advantage of naturally occurring processes to target a broad range of solid tumors. In circulation, self-assembled PA nanostructures disassemble and reassemble mainly with lipoproteins, which prolongs blood circulation and dramatically improves tumor accumulation and retention. Mechanistic studies suggested that PAs internalize into cancer cells by assembling with their cell membranes and independently of specific receptors. By exploiting these interactions, a PA developed in this study (namely Self-Assembly - Glutamic acid, SA-E) demonstrates specific accumulation in various xenograft, syngeneic, patient-derived xenograft, or transgenic rodent models. In addition, SA-E enabled the effective delivery of highly potent chemotherapy to different syngeneic and xenografted tumors with reduced side effects. With its simple and modular design and universal tumor accumulation mechanism, SA-E represents a promising platform for broad applications in cancer imaging and therapy.
Authors
- Bruce P. Branchaud (ORCID: https://orcid.org/0000-0002-8931-4801)
- Jared M. Fischer (ORCID: https://orcid.org/0000-0002-0062-0870)
- Adem Yıldırım (ORCID: https://orcid.org/0000-0001-6787-0148)
- Srivathsan Ranganathan (ORCID: https://orcid.org/0000-0002-0911-6590)
- Samuel Drennan (ORCID: https://orcid.org/0000-0003-0549-0689)
- Karla Bonic
- Arnaud Quentel (ORCID: https://orcid.org/0000-0002-5743-3056)
- Leslie L. Muldoon (ORCID: https://orcid.org/0000-0001-5583-2304)
- Benjamin R. Kingston (ORCID: https://orcid.org/0000-0003-1491-0366)
- Mingchong Dai (ORCID: https://orcid.org/0000-0002-4708-637X)
- Michael Henderson (ORCID: https://orcid.org/0000-0003-3636-9232)
- Sinan Sabuncu (ORCID: https://orcid.org/0000-0001-8346-8175)
- Ramon Barajas (ORCID: https://orcid.org/0000-0001-5093-4168)
- Isabel Dengos
- Xin Yi (ORCID: https://orcid.org/0000-0002-0220-3528)
- Florian Goncalves
- Li Xiang
- K. Mooney (ORCID: https://orcid.org/0009-0007-7818-4531)
- Morgan E. Stewart
- Samantha Holland
Institutions
- Oregon Health & Science University (US)
- Advanced Imaging Research (United States) (US)
Publication Details
- Journal
- Advanced Materials
- Published
- 2025-10-04
- DOI
- https://doi.org/10.1002/adma.202509359
- Citations
- 1
- Primary Topic
- Supramolecular Self-Assembly in Materials
- Type
- article
- Field-Weighted Citation Impact
- 0.60
Funders
- Oregon Health and Science University
- Texas Emerging Technology Fund
- Jerry M. Lewis, M.D. Mental Health Research Foundation
- National Institutes of Health
- National Cancer Institute