Targetable clinical nanoparticles for precision cancer therapy based on disease-specific molecular inflection points
Open accessAbstract
Novel translational approaches based on clinical modular nanoplatforms are needed in order to treat solid cancers according to their discrete molecular features. In the present study, we show that the clinical nanopharmaceutical Ferumoxytol, which consists of a glucose-based coat surrounding an iron oxide core, could identify molecular characteristics of prostate cancer, corresponding to unique phases of the disease continuum. By affixing a targeting probe for the prostate-specific membrane antigen on its surface, the nanopharmaceutical was able to assess the functional state of the androgen receptor pathway via MRI, guiding therapy and delivering it with the same clinical nanoparticle. In order to simultaneously inhibit signaling from key oncogenic pathways of more advanced forms of prostate cancer, a single-agent therapy for early stage disease to inhibit DNA replication, as well as combination therapy with two drugs co-retained within the nanopharmaceutical's polymeric coating, were tested and resulted in complete tumor ablation. Recalcitrant and terminal forms of the disease were effectively treated with a nanopharmaceutical delivering a combination that upregulates endoplasmic reticulum stress and inhibits metastasis, thereby showing that this multifunctional nanoplatform can be used in the clinic for patient stratification, as well as precision treatment based on the individual's unique disease features.
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Research works printed but not linked: 2
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Cited by
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Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications
Dadfar, S. M., Roemhild, K., Drude, N. I., von Stillfried, S., Knüchel, R., Kiessling, F., & Lammers, T. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.01.005 · Cited by 1,181 · see citing works
- Authors
- Kaittanis, C., Bolaender, A., Yoo, B., Shah, N., Ouerfelli, O., & Grimm, J.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Weill Cornell Medicine (US)
- Corresponding author
- Grimm, Jan
- Venue
- Nano Letters
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-10-23
- Volume
- 17
- Issue
- 11
- Pages
- 7160-7168
- ISSN
- 1530-6984 (ISSN-L)
- 1530-6992
- PMC
- PMC5677550
- OpenAlex
- W2767051565
- Cited by
- 19
- References
- 29
- Citations by year
- 2024: 3 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 6 · 2018: 2
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Nano Letters (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (1R01CA183953-01A1)
- National Institute of Biomedical Imaging and Bioengineering (R01EB017699)
- Memorial Sloan-Kettering Cancer Center
- Congressionally Directed Medical Research Programs (PC111617)
- Alex's Lemonade Stand Foundation for Childhood Cancer
- Prostate Cancer Foundation
- Commonwealth Foundation for Cancer Research
- Center for Molecular Imaging and Nanotechnology
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Keywords
- ferumoxytol, prostate cancer, prostate-specific membrane antigen, MRI-guided therapy, androgen receptor pathway, iron oxide nanoparticles, targeted drug delivery, combination therapy, DNA replication inhibition, endoplasmic reticulum stress, metastasis suppression, patient stratification, precision cancer therapy, solid tumors
- MeSH terms
- Animals, Antigens, Surface, Antineoplastic Agents, Drug Carriers, Humans, Magnetic Resonance Imaging, Male, Mice, Nude, Models, Molecular, Prostatic Neoplasms, Drug Delivery Systems, Glutamate Carboxypeptidase II, Cell Line, Tumor, Nanomedicine, Mice, Ferrosoferric Oxide, Nanoparticles, Precision Medicine
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