Evidence map›Paper›PMID 41321158›Full record

ArticleACS applied bio materials2025

Engineered Peptide Scrambling for Enhanced Drug Delivery to Resistant Breast Cancer Cells via Small Extracellular Vesicles.

Anika Babel, Joe Yuan, Najla A Saleh, Aimen Al-Hilfi, Sadhana Kilangodi, Jake Sun, Lelti Asgedom, Alicia Withrow, Assaf A Gilad, Masamitsu Kanada

Abstract read
In one paragraph

Article in ACS applied bio materials, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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.

Anika BabelInstitute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, Michigan 48824, United States.
Joe YuanDepartment of Chemical Engineering & Materials Science, Michigan State University, East Lansing, Michigan 48824, United States.
Najla A SalehInstitute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, Michigan 48824, United States.
Aimen Al-HilfiDepartment of Chemical Engineering & Materials Science, Michigan State University, East Lansing, Michigan 48824, United States.
Sadhana KilangodiInstitute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, Michigan 48824, United States.
Jake SunCollege of Osteopathic Medicine, Michigan State University, East Lansing, Michigan 48824, United States.
Lelti AsgedomCollege of Osteopathic Medicine, Michigan State University, East Lansing, Michigan 48824, United States.
Alicia WithrowCenter for Advanced Microscopy, Michigan State University, East Lansing, Michigan 48824, United States.
Assaf A GiladDepartment of Chemical Engineering & Materials Science, Michigan State University, East Lansing, Michigan 48824, United States.ORCID 0000-0002-7272-7570
Masamitsu KanadaInstitute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, Michigan 48824, United States.ORCID 0000-0001-9025-9582

Funding

Clinically Translatable MRI Reporter Genes and Imaging Methods with Ultra-High Specificity and SensitivityR01EB031008 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI CHRISTIAN T FARRAR · 2021 to 2026
$4.0M
Evolution and optimization of synthetic <READ/WRITE> function from and into cells using genetic programmingR01EB030565 · NIBIB · MICHIGAN STATE UNIVERSITY · PI BANZHAF, WOLFGANG, GILAD, ASSAF A · 2021 to 2024
$2.3M
Ultrasound-assisted extracellular vesicle engineering and induced release: EVEiRR21EB033554 · NIBIB · MICHIGAN STATE UNIVERSITY · PI KANADA, MASAMITSU · 2022 to 2024
$625k
NIBIB NIH HHS R01 EB030565NIBIB NIH HHS R01 EB031008NIBIB NIH HHS R21 EB033554
6 · The paper itself

Abstract

Extracellular vesicle (EV)-mediated transfer of biomolecules plays an essential role in intercellular communication and presents promising avenues for targeted drug delivery. Over the past decade, researchers have developed various approaches to modifying EV surfaces for targeting specific cells or tissues, including functionalization with targeting peptides to increase the specificity of drug delivery. Due to technical limitations, methods for characterizing the targeting moieties on the surface of small EVs (sEVs) are considerably restricted. To address these limitations and enhance the throughput capacity of sEV characterization, a dual-reporter platform was utilized to quantitatively assess the binding of tumor homing peptide (THP)-functionalized sEVs to breast cancer cells using bioluminescence assays and fluorescence microscopy. Twenty-four scrambled variants of the uPAR-binding peptide were designed for sEV engineering, and their uptake by MDA-MB-231 cells was evaluated in vitro. Our results revealed that amino acid scrambling generated both enhanced and reduced binding to cancer cells compared to the original peptide sequence. Furthermore, the data demonstrated that mechanical stimulation of EV producer HEK293FT cells enhanced the passive loading of methotrexate (MTX) into sEVs, but not large EVs, by increasing sEV production. By functionalizing MTX-loaded sEVs with a high-binding scrambled peptide, the delivery successfully surpassed the saturated free MTX uptake level in MDA-MB-231 cells, increasing cytotoxicity by 2.1-fold and providing a potent strategy for combating drug-resistant cancers. This study advances synthetic biology approaches to optimize tumor-targeted drug delivery, demonstrating that strategic peptide sequence scrambling can enhance targeting efficiency and drug delivery capabilities.

Indexed as

Antineoplastic AgentsBiocompatible MaterialsBreast NeoplasmsDrug Delivery SystemsExtracellular VesiclesMethotrexatePeptidesCell Line, TumorCell ProliferationCell SurvivalDrug Resistance, NeoplasmDrug Screening Assays, AntitumorFemaleHumansMaterials TestingParticle SizeAntineoplastic AgentsBiocompatible MaterialsMethotrexatePeptidesbioluminescencecancerchemotherapyextracellular vesiclefluorescencemethotrexate (MTX)tumor homing peptide

Identifiers

PMID41321158
PMCPMC12709616

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.