Evidence map›Paper›PMID 28566423›Full record

ArticleScience translational medicine2017

Radiation therapy primes tumors for nanotherapeutic delivery via macrophage-mediated vascular bursts.

Miles A Miller, Ravi Chandra, Michael F Cuccarese, Christina Pfirschke, Camilla Engblom, Shawn Stapleton, Utsarga Adhikary, Rainer H Kohler, James F Mohan, Mikael J Pittet and 1 more

Abstract read
In one paragraph

Article in Science translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed, 1 pooled it
13.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

117 citing papers in PubMed, 1 synthesis or guideline pooled it, 231 citations in OpenAlex.

  1. Pooled it
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  13. Smart Cancer Nanomedicine for Synergetic Therapy.Current medicinal chemistry · 2025
    Review
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  16. Systemically targeting monocytic myeloid-derived suppressor cells using dendrimers and their cell-level biodistribution kinetics.Journal of controlled release : official journal of the Controlled Release Society · 2024
    Article
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57 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Miles A MillerCenter for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA.ORCID 0000-0001-7638-8898
Ravi ChandraCenter for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA.
Michael F CuccareseCenter for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA.ORCID 0000-0001-7431-9573
Christina PfirschkeCenter for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA.
Camilla EngblomCenter for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA.
Shawn StapletonCenter for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA.ORCID 0000-0001-9966-068X
Utsarga AdhikaryCenter for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA.
Rainer H KohlerCenter for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA.ORCID 0000-0001-6269-6590
James F MohanCenter for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA.
Mikael J PittetCenter for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA.ORCID 0000-0002-2060-4691
Ralph WeisslederCenter for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA. rweissleder@mgh.harvard.edu.ORCID 0000-0003-0828-4143
Massachusetts General Hospital · USHarvard University · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Ramnik J Xavier · 1991 to 2026
$35.3M
Transgenic CoreP30DK057521 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI FLOREZ, JOSE CARLOS · 2000 to 2019
$31.4M
TRANSLATIONAL PHARMACOLOGY COREP50GM107618 · NIGMS · HARVARD MEDICAL SCHOOL · PI MALISZEWSKI, LAURA ELIZABETH · 2014 to 2018
$10.8M
Novel Clickdyes for Biomedical SensingR01EB010011 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI WEISSLEDER, MD, PHD, RALPH · 2010 to 2017
$3.1M
Imaging of nanotherapeutic drug actionU01CA206997 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WEISSLEDER, MD, PHD, RALPH · 2017 to 2021
$2.9M
Imaging tumor associated macrophage (TAM) functionR01CA206890 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI PITTET, MIKAEL, WEISSLEDER, MD, PHD, RALPH · 2017 to 2021
$1.9M
Single Cell In Vivo Imaging Technology to Analyze Taxane Nano Formulations in Breast CancerR00CA207744 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI MILLER, MILES A · 2018 to 2020
$747k
Single Cell In Vivo Imaging Technology to Analyze Taxane Nano Formulations in Breast CancerK99CA207744 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI MILLER, MILES A · 2016 to 2017
$359k
NCI NIH HHS K99 CA207744NCI NIH HHS R00 CA207744NCI NIH HHS R01 CA206890NCI NIH HHS U01 CA206997NIBIB NIH HHS R01 EB010011NIDDK NIH HHS P30 DK043351NIDDK NIH HHS P30 DK057521NIGMS NIH HHS P50 GM107618
6 · The paper itself

Abstract

Efficient delivery of therapeutic nanoparticles (TNPs) to tumors is critical in improving efficacy, yet strategies that universally maximize tumoral targeting by TNP modification have been difficult to achieve in the clinic. Instead of focusing on TNP optimization, we show that the tumor microenvironment itself can be therapeutically primed to facilitate accumulation of multiple clinically relevant TNPs. Building on the recent finding that tumor-associated macrophages (TAM) can serve as nanoparticle drug depots, we demonstrate that local tumor irradiation substantially increases TAM relative to tumor cells and, thus, TNP delivery. High-resolution intravital imaging reveals that after radiation, TAM primarily accumulate adjacent to microvasculature, elicit dynamic bursts of extravasation, and subsequently enhance drug uptake in neighboring tumor cells. TAM depletion eliminates otherwise beneficial radiation effects on TNP accumulation and efficacy, and controls with unencapsulated drug show that radiation effects are more pronounced with TNPs. Priming with combined radiation and cyclophosphamide enhances vascular bursting and tumoral TNP concentration, in some cases leading to a sixfold increase of TNP accumulation in the tumor, reaching 6% of the injected dose per gram of tissue. Radiation therapy alters tumors for enhanced TNP delivery in a TAM-dependent fashion, and these observations have implications for the design of next-generation tumor-targeted nanomaterials and clinical trials for adjuvant strategies.

Indexed as

Drug Delivery SystemsAnimalsCell CountCell Line, TumorChemistry, PharmaceuticalCombined Modality TherapyCyclophosphamideExtravasation of Diagnostic and Therapeutic MaterialsHumansIntravital MicroscopyMacrophagesMice, NudeNanoparticlesNeoplasmsPermeabilityPhagocytesCyclophosphamide

Identifiers

PMID28566423
PMCPMC6681815
OpenAlexW2620019303

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.