Evidence map›Paper›PMID 41416955›Full record

ArticleJournal of extracellular vesicles2025

Proteolysis Targeting Chimera Loaded Extracellular Vesicles for Developing Triple Negative Breast Cancer Treatment.

Nina Erwin, Umasankar De, Yufeng Xiao, Lei Wang, Chandra K Maharjan, Xiaoshu Pan, Ding Zuo, Nikee Awasthee, Guangrong Zheng, Daiqing Liao and 2 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of extracellular vesicles, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Nina ErwinDepartment of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.ORCID https://orcid.org/0000-0002-2692-3714
Umasankar DeDepartment of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA.
Yufeng XiaoDepartment of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Lei WangDepartment of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA.
Chandra K MaharjanDepartment of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA.
Xiaoshu PanDepartment of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Ding ZuoDepartment of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Nikee AwastheeDepartment of Anatomy & Cell Biology, College of Medicine, University of Florida, Gainesville, Florida, USA.
Guangrong ZhengDepartment of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Daiqing LiaoDepartment of Anatomy & Cell Biology, College of Medicine, University of Florida, Gainesville, Florida, USA.
Weizhou ZhangDepartment of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA.
Mei HeDepartment of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.ORCID https://orcid.org/0000-0001-5316-9326

Funding

Equipment Supplement to R35GM133794R35GM133794 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI Mei He · 2019 to 2026
$2.9M
Evaluation of High-throughput Extracellular Vesicle Loading Platform for Therapeutic Genome Editing INDsU01AI191208 · NIAID · UNIVERSITY OF FLORIDA · PI Mei He · 2025 to 2026
$1.4M
NIAID NIH HHS U01 AI191208NIGMS NIH HHS R35 GM133794NIH HHS 1R35GM133794NIH HHS NCICA260239NIH HHS NCICA26966NIH HHS NCICA290792NIH HHS NIAID U01AI191208
6 · The paper itself

Abstract

Proteolysis targeting chimeras (PROTACs) represent an emerging targeted cancer therapy approach. However, their poor cell penetration and instability in vivo pose daunting challenges for wide-spread clinical usage. To enhance the in vivo therapeutic efficacy of PROTACs, we introduced extracellular vesicles (EVs) for in vivo PROTAC delivery, which is leveraged by a novel microfluidic droplet-based EV electro-transfection system (μDES). We previously developed YX968 PROTAC, which can selectively degrade both HDAC3 and HDAC8 in triple negative breast cancer (TNBC) cells and effectively suppress the tumour cell growth without provoking global hyperacetylation. In this manuscript, we demonstrated that YX968 loaded EVs via the μDES system can retain the optimal integrity of drug loaded EVs with improved loading efficiency compared to other transfection approaches, which, in turn, significantly enhances the therapeutic function of PROTAC in vivo in TNBC mouse models. Intraperitoneal injections of YX968 loaded EVs led to significantly enhanced intratumoral degradation of HDAC3 and HDAC8 than YX986 alone, which resulted in advanced TNBC tumour inhibition without noticeable tissue toxicity. Such EV-based delivery strategy, with a scalable EV loading approach, enhanced the in vivo PROTAC drug stability and bioavailability and improved tissue penetration and targeting, filling an important gap in the clinical translation of PROTAC-based cancer therapy.

Indexed as

Extracellular VesiclesTriple Negative Breast NeoplasmsAnimalsCell Line, TumorFemaleHistone Deacetylase 3Histone Deacetylase InhibitorsHistone DeacetylasesHumansMiceProteolysisProteolysis Targeting ChimeraXenograft Model Antitumor AssaysHistone Deacetylase 3Histone Deacetylase InhibitorsHistone DeacetylasesProteolysis Targeting Chimeracancer therapyextracellular vesiclesPROTACTNBC

Identifiers

PMID41416955
PMCPMC12716143

What OpenQuestion holds

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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.