Evidence map›Paper›PMID 41993621›Full record

ArticleTheranostics2026

Tumor-targeted Exosomal Delivery of Celastrol for Enhanced Therapeutic Efficacy in NSCLC.

Disha Nagesh Moholkar, Raghuram Kandimalla, Mohd Saeed, Yaseera Arif, Neha Tyagi, Richa Singhal, Al-Hassan Kyakulaga, Amir Saeed, Margaret Wallen, Ramesh Gupta and 1 more

Abstract read
In one paragraph

Article in Theranostics, 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

11 authors.

Disha Nagesh MoholkarBrown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Raghuram KandimallaBrown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Mohd SaeedDepartment of Biology College of Sciences, University of Hail, Hail, Saudi Arabia.
Yaseera ArifBrown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Neha TyagiBrown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Richa SinghalDepartment of Medicine, University of Louisville, Louisville, KY 40202, USA.
Al-Hassan KyakulagaBrown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Amir SaeedDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail, Saudi Arabia.
Margaret Wallen3P Biotechnologies Inc., Louisville, KY 40202, USA.
Ramesh GuptaBrown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Farrukh AqilBrown Cancer Center, University of Louisville, Louisville, KY 40202, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rationale: Non-small cell lung cancer (NSCLC) continues to impose a significant global mortality burden, due to limited therapies, drug resistance, and treatment-related toxicity. Exosomes offer promise for the targeted delivery of therapeutic agents. Methods: Exosomes were isolated from bovine colostrum and characterized for size, polydispersity index, and surface charge. Celastrol (CEL) was loaded onto exosomes (ExoCEL), and Folic Acid (FA)-functionalized exosomes (FA-ExoCEL) and validated using fluorescence quenching and protease sensitivity assay. Anticancer activity was assessed in NSCLC cell lines using colony formation, cell migration and uptake assays. Transcriptomic (RNA-seq) and protein analysis were performed to analyze gene expression changes. Biodistribution, oral uptake and potential toxicity were evaluated in wild-type mice, while oral antitumor efficacy was tested in orthotopic lung tumor models comparing CEL, ExoCEL and FA-ExoCEL. Synergistic activity with paclitaxel was assessed in chemoresistant cells. Results: Exosomes were isolated, characterized and efficiently loaded with CEL. ExoCEL demonstrated superior antiproliferative effects in NSCLC cell lines and enhanced potency in drug-resistant A549TR cells compared to free CEL. ExoCEL significantly inhibited colony formation and cell migration in a dose-dependent manner. RNA Seq and protein analyses showed that CEL and ExoCEL reversed TGF-β-induced EMT, restored epithelial markers, suppressed mesenchymal, oncogenic and extracellular matrix related markers. In orthotopic lung tumor models, FA-ExoCEL achieved approximately 80-90% tumor inhibition, outperforming both free CEL and ExoCEL. Oral delivery of FA-ExoCEL resulted in efficient gastrointestinal uptake, selective tumor targeting, recovery of exosomal markers in circulation and no observed systemic toxicity. CEL exhibited strong synergy with paclitaxel, with exosomal delivery further enhancing paclitaxel efficacy in resistant cells. Conclusions: FA-ExoCEL represents a safe, scalable, and effective oral therapeutic strategy for NSCLC. By combining exosome-mediated delivery with folate-targeted tumor accumulation, this platform enhances CEL bioavailability, and improves antitumor efficacy, supporting its translational potential for lung cancer therapy.

Indexed as

Antineoplastic AgentsCarcinoma, Non-Small-Cell LungExosomesLung NeoplasmsPentacyclic TriterpenesAnimalsCattleCell Line, TumorCell MovementDrug Delivery SystemsFemaleFolic AcidHumansMicePaclitaxelXenograft Model Antitumor AssaysAntineoplastic AgentscelastrolFolic AcidPaclitaxelPentacyclic TriterpenesCelastrolChemoresistanceEpithelial-to-mesenchymal transition (EMT)ExosomesLung cancer.Oral targeted delivery

Identifiers

PMID41993621
PMCPMC13080336

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.