Evidence map›Paper›PMID 42144617›Full record

ArticleJournal of nanobiotechnology2026

Multitargeted nanoparticles inhibit cancer invasion by disrupting cancer-associated fibroblast-tumor cell crosstalk and modulating collagen pattern and EMT.

Liting Wang, Pei Zhi, Ibrahim Alradwan, Chunsheng He, Azhar Z Abbasi, Han Gao, Andrew M Rauth, David W Cescon, Jeffrey T Henderson, Xiao Yu Wu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of nanobiotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Liting Wang *Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, M5S3M2, ON, Canada.
Pei Zhi *Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, M5S3M2, ON, Canada.
Ibrahim AlradwanAdvanced Pharmaceutics and Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, M5S3M2, ON, Canada.
Chunsheng HeAdvanced Pharmaceutics and Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, M5S3M2, ON, Canada.
Azhar Z AbbasiAdvanced Pharmaceutics and Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, M5S3M2, ON, Canada.
Han GaoAdvanced Pharmaceutics and Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, M5S3M2, ON, Canada.
Andrew M RauthDepartments of Medical Biophysics and Radiation Oncology, University of Toronto, 610 University Ave, Toronto, M5G2M9, ON, Canada.
David W CesconDepartment of Medical Oncology and Hematology, Princess Margaret Cancer Centre/University Health Network, 700 University Ave, Toronto, M5G2M9, ON, Canada.
Jeffrey T HendersonAdvanced Pharmaceutics and Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, M5S3M2, ON, Canada.
Xiao Yu WuAdvanced Pharmaceutics and Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, M5S3M2, ON, Canada. sxy.wu@utoronto.ca.

Funding

Canadian Institutes of Health Research (CIHR) Project Grant #PJT-168872Natural Sciences & Engineering Research Council of Canada (NSERC) Discovery Grant RGPIN-2025-07078Natural Sciences & Engineering Research Council of Canada (NSERC) Equipment Grant EQPEQ 440689-13
6 · The paper itself

Abstract

backgroundCancer-associated fibroblasts (CAFs), a major component of tumor stroma, play an important role in tumor progression and metastasis via paracrine signaling, extracellular matrix (ECM) remodelling, and the secretion of growth factors, cytokines, and chemokines promoting tumor growth. In this study, we aim to develop a multitargeted nanoparticle formulation to simultaneously target CAFs and triple negative breast cancer (TNBC) cells, aiming to block their crosstalk, remodel the ECM, and inhibit epithelial-mesenchymal transition (EMT) to suppress tumor growth and metastatic processes.

methodsThe potential of CAFs as therapeutic target for TNBC was evaluated by analyzing RNA-seq data from TNBC patients. A novel iRGD-functionalized polymer-lipid hybrid nanoparticle (iRGD-DOX-oHA-PLN) was specifically designed to target αvβ3 and αvβ5 receptors on both tumor cells and CAFs. A murine TNBC cell line and its orthotopic in vivo model were used for efficacy evaluation. Within this model, a murine fibroblast cell line was incorporated as a source of CAFs for in vitro investigation of the crosstalk between CAFs and tumor cells. In addition, the mechanism of iRGD-DOX-oHA-PLN nanoparticles in disrupting CAF-tumor cell interactions by blocking downstream features associated with metastases including paracrine communication, collagen organization and epithelial-mesenchymal transition (EMT) associated with metastasis were investigated both in vitro and in vivo.

resultsThe iRGD-DOX-oHA-PLN demonstrates higher cellular uptake and cytotoxicity in CAFs overexpressing integrins αvβ3 and αvβ5 compared to normal fibroblasts. The results demonstrate that iRGD-DOX-oHA-PLN significantly restricts the interaction of CAFs and cancer cells, due to interruption of paracrine communication induced by pro-metastatic TGF-β and CXCL12 secretion together with a reduction of CXCR4 expression. Consistent with the in vitro results, in an orthotopic syngeneic TNBC murine model, iRGD-DOX-oHA-PLN effectively depletes CAFs, reducing tumor-associated collagen production, and altering tumor-associated collagen signatures (TACS). Thus, iRGD-DOX-oHA-PLN treatment impedes tumor invasion by reducing MMP-9 secretion and inhibiting EMT.

conclusionThe data reveals that simultaneously targeting CAFs and tumor cells, while blocking their crosstalk via application of a multitargeted nanomedicine, offers a compelling and effective strategy to inhibit metastasis of TNBC.

Indexed as

Antineoplastic AgentsCancer-Associated FibroblastsCollagenEpithelial-Mesenchymal TransitionNanoparticlesTriple Negative Breast NeoplasmsAnimalsCell Line, TumorFemaleHumansMiceNeoplasm InvasivenessAntineoplastic AgentsCollagenCAF-cancer interactionsCancer-associated fibroblast (CAF)Epithelial-mesenchymal transitionMultitargeted nanoparticlesTriple negative breast cancerTumor-associated collagen signaturesTumor microenvironment

Identifiers

PMID42144617
PMCPMC13359549

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.