Evidence map›Paper›PMID 40204039›Full record

ArticleInternational journal of pharmaceutics2025

Targeting EGFR-TKI resistance in lung cancer: Role of miR-5193/miR-149-5p loaded NK-EVs and Carboplatin combination.

Aakash Nathani, Li Sun, Yan Li, Jassy Lazarte, Mounika Aare, Mandip Singh

Abstract read
In one paragraph

Article in International journal of pharmaceutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. NK-derived exosomes in anti-tumor strategies.Medical oncology (Northwood, London, England) · 2025
    Review
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

6 authors.

Aakash NathaniCollege of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA.
Li SunDepartment of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL, USA; Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, USA.
Yan LiDepartment of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL, USA.
Jassy LazarteCollege of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA.
Mounika AareCollege of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA.
Mandip SinghCollege of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA. Electronic address: mandip.sachdeva@famu.edu.

Funding

Research Project-3: Effectiveness of an eHealth intervention for uptake of cervical cancer screening in Hispanic womenU54MD007582 · NIMHD · FLORIDA AGRICULTURAL AND MECHANICAL UNIV · PI KINFE KEN REDDA · 2019 to 2026
$28.1M
Engineering Extracellular Vesicles of Human Brain Organoids for Stroke TherapyR01NS125016 · NINDS · FLORIDA STATE UNIVERSITY · PI Yan Li · 2022 to 2026
$1.8M
Exosomal Based micro RNA delivery for Resistant Lung CancerR16GM149462 · NIGMS · FLORIDA AGRICULTURAL AND MECHANICAL UNIV · PI Mandip Singh Sachdeva · 2023 to 2026
$592k
NIGMS NIH HHS R16 GM149462NIMHD NIH HHS U54 MD007582NINDS NIH HHS R01 NS125016
6 · The paper itself

Abstract

Lung cancer remains the leading cause of cancer-related deaths, and there is an urgent need for innovative therapies. MicroRNA (miRNA)-based gene therapy has shown promise, but efficient delivery systems are required for its success. This study investigates the use of extracellular vehicles (EVs) secreted by natural killer (NK) cells as delivery systems for miRNAs targeting PD-L1/PD-1 immune checkpoint and FOXM1, in combination with Carboplatin, to enhance anticancer efficacy in lung cancer models. NK-EVs were isolated from NK92-MI cells and characterized using nanoparticle tracking analysis (NTA), proteomics and Western blotting, confirming their exosomal characteristics. Gene ontology profiling and RNA-seq identified highly expressed miRNAs such as miR-5193 and miR-149-5p, which were loaded into NK-EVs via electroporation. Agarose gel electrophoresis confirmed their entrapment and Quickdrop spectrophotometer was used to estimate the quantity. In vitro, miRNA-loaded NK-EVs demonstrated significant cytotoxicity against Osimertinib-resistant PDX (TM0019, Jackson Labs) and H1975R (with L858R mutations) lung cancer cells, with approximately 1.2 to 1.6-fold (p < 0.01) decrease in cell viability compared to NK-EVs alone. In vivo, the combination of miRNA-loaded NK-EVs and Carboplatin significantly reduced tumor volumes (3.5 to 4-fold, p < 0.001) in PDX and H1975R xenograft models, with the most pronounced effect observed in combination therapies. Western blot analysis showed downregulation of tumor-associated markers: PD-1/PD-L1, FOXM1, Survivin, NF-κB and others vs untreated group, p < 0.001) suggesting immune checkpoint inhibition, apoptosis and anti-inflammatory activity. These findings highlight the potential of NK-EVs as effective carriers for miRNAs in combination with chemotherapy, offering a promising therapeutic strategy for NSCLC with EGFR mutations.

Indexed as

CarboplatinExtracellular VesiclesKiller Cells, NaturalLung NeoplasmsMicroRNAsAcrylamidesAniline CompoundsAnimalsAntineoplastic AgentsB7-H1 AntigenCell Line, TumorDrug Resistance, NeoplasmErbB ReceptorsForkhead Box Protein M1HumansIndolesAcrylamidesAniline CompoundsAntineoplastic AgentsB7-H1 AntigenCarboplatinCD274 protein, humanEGFR protein, humanErbB ReceptorsForkhead Box Protein M1FOXM1 protein, humanIndolesMicroRNAsMIRN149 microRNA, humanosimertinibProgrammed Cell Death 1 ReceptorPyrimidinesEGFR mutationFOXM1miR-149-5pmiR-5193NK-EVsNSCLCOsimertinib resistancePD-L1/PD-1 axis

Identifiers

PMID40204039
PMCPMC12706798

What Socratic 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 Socratic graph.