Cited by 506Nanoparticle-Based Drug DeliveryNanoplatforms for cancer theranosticsDendrimers and Hyperbranched Polymers

The Use of Alternative Strategies for Enhanced Nanoparticle Delivery to Solid Tumors

Open access
Izci, Mukaddes, Maksoudian, Christy, Manshian, Bella B., Soenen, Stefaan J.·2021·Chemical Reviews

Abstract

Abstract Nanomaterial (NM) delivery to solid tumors has been the focus of intense research for over a decade. Classically, scientists have tried to improve NM delivery by employing passive or active targeting strategies, making use of the so-called enhanced permeability and retention (EPR) effect. This phenomenon is made possible due to the leaky tumor vasculature through which NMs can leave the bloodstream, traverse through the gaps in the endothelial lining of the vessels, and enter the tumor. Recent studies have shown that despite many efforts to employ the EPR effect, this process remains very poor. Furthermore, the role of the EPR effect has been called into question, where it has been suggested that NMs enter the tumor via active mechanisms and not through the endothelial gaps. In this review, we provide a short overview of the EPR and mechanisms to enhance it, after which we focus on alternative delivery strategies that do not solely rely on EPR in itself but can offer interesting pharmacological, physical, and biological solutions for enhanced delivery. We discuss the strengths and shortcomings of these different strategies and suggest combinatorial approaches as the ideal path forward.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1021/acs.chemrev.0c00779

Cites

527 of 527 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Tumors in humans are poorly diagnosed in the initial stages, which is mainly responsible for the limiting effects of EPR after drug release.

    “Tumors in humans are poorly diagnosed in the initial stages, which is mainly responsible for the limiting effects of EPR after drug release [102].”

    From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [102]

    The Personalized Medicine section (page unavailable) says that EPR effects vary substantially among patients, limiting the clinical translation of nanomedicines. It also identifies drug release as one factor affecting treatment response. It does not say that human tumors are poorly diagnosed at initial stages or that late diagnosis is the main reason for EPR’s limitations after drug release. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. de Wolf H. K.; Snel C. J.; Verbaan F. J.; Schiffelers R. M.; Hennink W. E.; Storm G. Effect of Cationic Carriers on the Pharmacokinetics and Tumor Localization of Nucleic Acids after Intravenous Administration. Int. J. Pharm. 2007, 331, 167– 175. 10.1016/j.ijpharm.2006.10.029. 17134859 · DOI

Cited by

Sorted by citations

Authors
Izci, M., Maksoudian, C., Manshian, B. B., & Soenen, S. J.
Affiliations
KU Leuven (BE)
Corresponding author
Soenen, Stefaan J.
Venue
Chemical Reviews
Published
2021-01-14
Volume
121
Issue
3
Pages
1746-1803
ISSN
  • 0009-2665 (ISSN-L)
  • 1520-6890
OpenAlex
W3118474372
Cited by
506
References
527
Citations by year
2026: 81 · 2025: 91 · 2024: 109 · 2023: 96 · 2022: 94 · 2021: 35
FWCI
5.77
Type
journal article
Language
en
Open access
Locations
  • Chemical Reviews (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Lirias (submittedVersion, other-oa)
Funders
  • H2020 European Research Council (757398)
  • Fonds Wetenschappelijk Onderzoek (G0B2919N)
  • Bijzonder Onderzoeksfonds (3M180306)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
  • Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
Keywords
nanoparticle delivery, solid tumors, enhanced permeability and retention effect, tumor vasculature, active targeting, passive targeting, tumor endothelium
MeSH terms
Animals, Humans, Neoplasms, Peptides, Drug Delivery Systems, Nanoparticles, Tumor Microenvironment

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review