Targetable clinical nanoparticles for precision cancer therapy based on disease-specific molecular inflection points Journal Article

Authors: Kaittanis, C.; Bolaender, A.; Yoo, B.; Shah, N.; Ouerfelli, O.; Grimm, J.
Article Title: Targetable clinical nanoparticles for precision cancer therapy based on disease-specific molecular inflection points
Abstract: 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. © 2017 American Chemical Society.
Keywords: molecular imaging; urology; cell membranes; nanoparticles; combination therapy; patient treatment; disease control; diseases; iron oxides; molecular characteristics; psma; endoplasmic reticulum stress; polymeric coatings; oncogenic pathways; prostate-specific membrane antigens; androgen receptors
Journal Title: Nano Letters
Volume: 17
Issue: 11
ISSN: 1530-6984
Publisher: American Chemical Society  
Date Published: 2017-11-08
Start Page: 7160
End Page: 7168
Language: English
DOI: 10.1021/acs.nanolett.7b04209
PROVIDER: scopus
PMCID: PMC5677550
PUBMED: 29035540
Notes: Article -- Export Date: 4 December 2017 -- Source: Scopus
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MSK Authors
  1. Nilesh Shah
    2 Shah
  2. Jan Grimm
    54 Grimm
  3. Barney Yoo
    9 Yoo