Antibody fragment-conjugated polymeric micelles incorporating platinum drugs for targeted therapy of pancreatic cancer
Abstract
Antibody-mediated therapies including antibody-drug conjugates (ADCs) have shown much potential in cancer treatment by tumor-targeted delivery of cytotoxic drugs. However, there is a limitation of payloads that can be delivered by ADCs. Integration of antibodies to drug-loaded nanocarriers broadens the applicability of antibodies to a wide range of therapeutics. Herein, we developed antibody fragment-installed polymeric micelles via maleimide-thiol conjugation for selectively delivering platinum drugs to pancreatic tumors. By tailoring the surface density of maleimide on the micelles, one tissue factor (TF)-targeting Fab' was conjugated to each carrier. Fab'-installed platinum-loaded micelles exhibited more than 15-fold increased cellular binding within 1 h and rapid cellular internalization compared to non-targeted micelles, leading to superior in vitro cytotoxicity. In vivo, Fab'-installed micelles significantly suppressed the growth of pancreatic tumor xenografts for more than 40 days, outperforming non-targeted micelles and free drugs. These results indicate the potential of Fab'-installed polymeric micelles for efficient drug delivery to solid tumors.
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DACHPt/m demonstrated rapid cellular internalisation, enhanced in vitro cytotoxicity, and effectively inhibited the growth of pancreatic tumour xenografts in vivo, surpassing non-targeted micelles.
“Notably, DACHPt/m demonstrated rapid cellular internalisation, resulting in enhanced in vitro cytotoxicity and effectively inhibiting the growth of pancreatic tumour xenografts in vivo, surpassing both non-targeted micelles and”
From Advances in platinum-based cancer therapy: overcoming platinum resistance through rational combinatorial strategies (2025) · cites this paper as [77]
Ahn et al. nanomicelles conjugated with antitissue factor antibody (TF) burdened with platinum drugs demonstrate 15-fold greater cellular uptake and substantial anticancer outcome for more than 40 days in pancreatic cancer than nontargeted micelles.
“These nanomicelles demonstrate 15-fold greater cellular uptake and substantial anticancer outcome for extra than 40 days in pancreatic cancer than nontargeted micelles.”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [119]
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“have organized new nanomicelles conjugated antitissue factor antibody (TF) burdened with platinum drugs [119].”
BackgroundYusoh, N. A., Ahmad, H., Vallis, K. A., & Gill, M. R. (2025) · Medical Oncology · doi:10.1007/s12032-025-02812-3 · Cited by 40 · see citing works
- Authors
- Ahn, J., Miura, Y., Yamada, N., Chida, T., Liu, X., Kim, A., Sato, R., Tsumura, R., Koga, Y., Yasunaga, M., Nishiyama, N., Matsumura, Y., Cabral, H., & Kataoka, K.
- Affiliations
- The University of Tokyo (JP)
- Center for Disease Biology and Integrative Medicine, The University of Tokyo (JP)
- Tokyo Institute of Technology (JP)
- National Cancer Centre Japan (JP)
- Corresponding author
- Kataoka, Kazunori
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 39
- Pages
- 23-30
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W1992899738
- Cited by
- 147
- References
- 51
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 6 · 2023: 8 · 2022: 9 · 2021: 12 · 2020: 20 · 2019: 12 · 2018: 11 · 2017: 21 · 2016: 22 · 2015: 12
- FWCI
- 6.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (JSPS)
- Japanese Ministry of Health, Labor, and Welfare (MHLW)
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Grants-in-Aid for Young Scientists (23700526, 25750172, 24689051)
- Challenging Exploratory Research (24659584)
- Initiative for Accelerating Regulatory Science in Innovative Drug, Medical Device, and Regenerative Medicine
- National Cancer Center Research and Development Fund
- Health and Labour Sciences Research Grants
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- polymeric micelles, FAB, platinum drugs, targeted drug delivery, pancreatic cancer, tissue factor, thiol-maleimide conjugation, tumor targeting, cellular internalization, tumor xenografts, antibody-drug conjugates
- MeSH terms
- Animals, Antineoplastic Agents, Humans, Immunoglobulin Fragments, Immunoglobulin Fab Fragments, Micelles, Pancreatic Neoplasms, Platinum, Polymers, Microscopy, Confocal, Cell Line, Tumor, Mice, Nanoparticles
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