Improving nanotherapy delivery and action through image-guided systems pharmacology

Ng, Thomas S.C.; Garlin, Michelle A.; Weissleder, Ralph; Miller, Miles A.

doi:10.7150/thno.37215

Cited by 60Nanoparticle-Based Drug DeliveryNanoplatforms for cancer theranosticsUltrasound and Hyperthermia Applications

Improving nanotherapy delivery and action through image-guided systems pharmacology

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Ng, Thomas S.C., Garlin, Michelle A., Weissleder, Ralph, Miller, Miles A.·2020·Theranostics

DOI 10.7150/thno.37215PMC PMC6956809

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Abstract

Despite recent advances in the translation of therapeutic nanoparticles (TNPs) into the clinic, the field continues to face challenges in predictably and selectively delivering nanomaterials for the treatment of solid cancers.The concept of enhanced permeability and retention (EPR) has been coined as a convenient but simplistic descriptor of high TNP accumulation in some tumors.However, in practice EPR represents a number of physiological variables rather than a single one (including dysfunctional vasculature, compromised lymphatics and recruited host cells, among other aspects of the tumor microenvironment) -each of which can be highly heterogenous within a given tumor, patient and across patients.Therefore, a clear need exists to dissect the specific biophysical factors underlying the EPR effect, to formulate better TNP designs, and to identify patients with high-EPR tumors who are likely to respond to TNP.The overall pharmacology of TNP is governed by an interconnected set of spatially defined and dynamic processes that benefit from a systems-level quantitative approach, and insights into the physiology have profited from the marriage between in vivo imaging and quantitative systems pharmacology (QSP) methodologies.In this article, we review recent developments pertinent to image-guided systems pharmacology of nanomedicines in oncology.We first discuss recent developments of quantitative imaging technologies that enable analysis of nanomaterial pharmacology at multiple spatiotemporal scales, and then examine reports that have adopted these imaging technologies to guide QSP approaches.In particular, we focus on studies that have integrated multi-scale imaging with computational modeling to derive insights about the EPR effect, as well as studies that have used modeling to guide the manipulation of the EPR effect and other aspects of the tumor microenvironment for improving TNP action.We anticipate that the synergistic combination of imaging with systems-level computational methods for effective clinical translation of TNPs will only grow in relevance as technologies increase in resolution, multiplexing capability, and in the ability to examine heterogeneous behaviors at the single-cell level.

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A synergistic combination of multiscale imaging with computational modeling may enhance knowledge of the EPR effect.
“Thus, a synergistic combination of multiscale imaging with computational modeling may enhance the knowledge of the EPR effect [18].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [18]
Determinants of the EPR effect and nanodrug performance happen across manifold spatial and temporal scales ranging from systemic biodistribution to delivery and consequences upon distinct cells.
“Determinants of the EPR effect and nanodrug performance happen across manifold spatial and temporal scales ranging from systemic biodistribution of nanodrugs to their delivery and consequences upon distinct cells (Figure 3) [18].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [18]

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[19]Fein MR Wysocki RW Egeblad M Cancer in the Spotlight: Using Intravital Imaging in Cancer Research Advances in Intravital Microscopy: From Basic to Clinical Research, in R Weigert, ed Dordrecht, Springer Netherlands 2014 105 123

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Authors: Ng, T. S. C., Garlin, M. A., Weissleder, R., & Miller, M. A.
Affiliations: Brigham and Women's Hospital (US)
Massachusetts General Hospital (US)
Harvard University (US)
Corresponding author: Weissleder, Ralph
Miller, Miles A.
ORCID: Ng, Thomas S.C.
Weissleder, Ralph
Miller, Miles A.
Venue: Theranostics
Publisher: Ivyspring International Publisher
Published: 2020
Volume: 10
Issue: 3
Pages: 968-997
ISSN: 1838-7640 (ISSN-L)
DOI: 10.7150/thno.37215
PMC: PMC6956809
OpenAlex: W2994483481
Cited by: 60
References: 202
Citations by year: 2026: 5 · 2025: 7 · 2024: 4 · 2023: 9 · 2022: 8 · 2021: 13 · 2020: 13 · 2019: 1
FWCI: 0.56
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Theranostics (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Institutes of Health (UO1CA206997)
National Cancer Institute (R00CA207744, U01CA206997, T32CA079443)
Topics: Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
Keywords: nanotherapeutics, nanomedicine, enhanced permeability and retention effect, tumor microenvironment, quantitative systems pharmacology, multiscale imaging, tumor vasculature, lymphatic dysfunction, tumor heterogeneity, solid tumors, cancer nanotherapy, computational modeling
MeSH terms: Theranostic Nanomedicine, Animals, Antineoplastic Agents, Humans, Neoplasms, Drug Delivery Systems, Nanoparticles

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Improving nanotherapy delivery and action through image-guided systems pharmacology

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