---
title: "Vorinostat-loaded PLGA-PEG-AEAA Nanocarrier Enhances Targeted Therapy for Colorectal Cancer"
id: "pubmed-42546991"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42546991"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42546991/"
doi: "10.1016/j.ijpharm.2026.127274"
published_at: "2026-09-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Vorinostat-loaded PLGA-PEG-AEAA Nanocarrier Enhances Targeted Therapy for Colorectal Cancer
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42546991
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42546991/)
- **DOI:** [10.1016/j.ijpharm.2026.127274](https://doi.org/10.1016%2Fj.ijpharm.2026.127274)
- **Published At:** 2026-09-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Colorectal cancer (CRC) is a leading cause of cancer death worldwide; Histone deacetylase (HDAC) inhibitors such as **vorinostat** induce cell cycle arrest and apoptosis and are promising anticancer agents. - Clinical use of vorinostat in solid tumors is limited by rapid systemic clearance, poor tumor distribution, and off-target delivery. - The authors developed a targeted nanoformulation (T-NP.VOR) based on a **PLGA-PEG-AEAA** carrier; AEAA (aminoethyl anisamide) is used for targeting. - In vitro, T-NP.VOR increased cellular uptake by CRC cells via **Sigma‑1 receptor**-mediated internalization, producing enhanced HDAC inhibition, cell cycle blockade, and apoptosis compared with free drug or non-targeted nanoparticles. - In an orthotopic CRC mouse model, T-NP.VOR prolonged blood circulation and improved tumor distribution relative to free vorinostat and a non-targeted nanoformulation. - Improved pharmacokinetics and tumor delivery of T-NP.VOR translated into significant tumor growth suppression and extended survival in treated animals. - The study supports the **PLGA-PEG-AEAA** nanocarrier as a promising platform for targeted delivery of vorinostat in CRC therapy. - Specific experimental details (e.g., exact dosing, quantitative uptake metrics, statistical values) and full methodological parameters were not reported in the PubMed abstract and require consultation of the full text for confirmation.
## Clinical Analysis & Structured Key Points
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Epub 2026 Aug 3. # Vorinostat nanoformulation triggers cell cycle blockade and apoptosis for colorectal cancer therapy [Leilei Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+L&cauthor_id=42546991)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#full-view-affiliation-1 "School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China."), [Tingting Guo](https://pubmed.ncbi.nlm.nih.gov/?term=Guo+T&cauthor_id=42546991)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#full-view-affiliation-2 "Department of Pharmacy, the Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China."), [Junjun Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+J&cauthor_id=42546991)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#full-view-affiliation-3 "Department of Pharmacy, The Second Hospital of Jilin University, Changchun 130041, China."), [Yifang Zou](https://pubmed.ncbi.nlm.nih.gov/?term=Zou+Y&cauthor_id=42546991)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#full-view-affiliation-1 "School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China."), [Hao Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+H&cauthor_id=42546991)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#full-view-affiliation-4 "Department of Hepatopathy, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China."), [Xinyuan Fan](https://pubmed.ncbi.nlm.nih.gov/?term=Fan+X&cauthor_id=42546991)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#full-view-affiliation-5 "School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China; Department of Gastrointestinal and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, China."), [Huaiying Qin](https://pubmed.ncbi.nlm.nih.gov/?term=Qin+H&cauthor_id=42546991)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#full-view-affiliation-1 "School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China."), [Yujie Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+Y&cauthor_id=42546991)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#full-view-affiliation-1 "School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China."), [Shulan Han](https://pubmed.ncbi.nlm.nih.gov/?term=Han+S&cauthor_id=42546991)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#full-view-affiliation-1 "School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China."), [Zhuo Yu](https://pubmed.ncbi.nlm.nih.gov/?term=Yu+Z&cauthor_id=42546991)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#full-view-affiliation-4 "Department of Hepatopathy, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China."), [Jiaxing Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+J&cauthor_id=42546991)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#full-view-affiliation-6 "Department of Gastrointestinal and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, China. Electronic address: jiaxingyang@jlu.edu.cn."), [Jianfeng Guo](https://pubmed.ncbi.nlm.nih.gov/?term=Guo+J&cauthor_id=42546991)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#full-view-affiliation-7 "School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China. Electronic address: jguo@jlu.edu.cn.") Affiliations Expand ### Affiliations * 1 School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China. * 2 Department of Pharmacy, the Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China. * 3 Department of Pharmacy, The Second Hospital of Jilin University, Changchun 130041, China. * 4 Department of Hepatopathy, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. * 5 School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China; Department of Gastrointestinal and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, China. * 6 Department of Gastrointestinal and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, China. Electronic address: jiaxingyang@jlu.edu.cn. * 7 School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China. Electronic address: jguo@jlu.edu.cn. * PMID: **42546991** * DOI: [ 10.1016/j.ijpharm.2026.127274 ](https://doi.org/10.1016/j.ijpharm.2026.127274) Item in Clipboard # Vorinostat nanoformulation triggers cell cycle blockade and apoptosis for colorectal cancer therapy Leilei Yang et al. Int J Pharm. 2026. Show details Display options Display options Format Abstract PubMed PMID Int J Pharm Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Int+J+Pharm%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Int+J+Pharm%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42546991/) . 2026 Sep 5:702:127274. doi: 10.1016/j.ijpharm.2026.127274. Epub 2026 Aug 3. ### Authors [Leilei Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+L&cauthor_id=42546991)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#short-view-affiliation-1 "School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China."), [Tingting Guo](https://pubmed.ncbi.nlm.nih.gov/?term=Guo+T&cauthor_id=42546991)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#short-view-affiliation-2 "Department of Pharmacy, the Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China."), [Junjun Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+J&cauthor_id=42546991)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#short-view-affiliation-3 "Department of Pharmacy, The Second Hospital of Jilin University, Changchun 130041, China."), [Yifang Zou](https://pubmed.ncbi.nlm.nih.gov/?term=Zou+Y&cauthor_id=42546991)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#short-view-affiliation-1 "School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China."), [Hao Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+H&cauthor_id=42546991)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#short-view-affiliation-4 "Department of Hepatopathy, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China."), [Xinyuan Fan](https://pubmed.ncbi.nlm.nih.gov/?term=Fan+X&cauthor_id=42546991)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#short-view-affiliation-5 "School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China; Department of Gastrointestinal and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, China."), [Huaiying Qin](https://pubmed.ncbi.nlm.nih.gov/?term=Qin+H&cauthor_id=42546991)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#short-view-affiliation-1 "School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China."), [Yujie Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+Y&cauthor_id=42546991)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#short-view-affiliation-1 "School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China."), [Shulan Han](https://pubmed.ncbi.nlm.nih.gov/?term=Han+S&cauthor_id=42546991)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#short-view-affiliation-1 "School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China."), [Zhuo Yu](https://pubmed.ncbi.nlm.nih.gov/?term=Yu+Z&cauthor_id=42546991)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#short-view-affiliation-4 "Department of Hepatopathy, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China."), [Jiaxing Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+J&cauthor_id=42546991)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#short-view-affiliation-6 "Department of Gastrointestinal and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, China. Electronic address: jiaxingyang@jlu.edu.cn."), [Jianfeng Guo](https://pubmed.ncbi.nlm.nih.gov/?term=Guo+J&cauthor_id=42546991)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42546991/#short-view-affiliation-7 "School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China. Electronic address: jguo@jlu.edu.cn.") ### Affiliations * 1 School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China. * 2 Department of Pharmacy, the Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China. * 3 Department of Pharmacy, The Second Hospital of Jilin University, Changchun 130041, China. * 4 Department of Hepatopathy, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. * 5 School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China; Department of Gastrointestinal and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, China. * 6 Department of Gastrointestinal and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, China. Electronic address: jiaxingyang@jlu.edu.cn. * 7 School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China. Electronic address: jguo@jlu.edu.cn. * PMID: **42546991** * DOI: [ 10.1016/j.ijpharm.2026.127274 ](https://doi.org/10.1016/j.ijpharm.2026.127274) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Histone deacetylase (HDAC) inhibitors such as vorinostat (VOR) eventuate cell cycle arrest and apoptosis by suppressing the HDAC activity, representing a promising class of anti-cancer agents. The clinical application of VOR in solid tumors (e.g., CRC) is hindered by rapid circulatory clearance, insufficient tumor distribution, and off-target cell delivery. To overcome these limitations, we constructed a targeted nanoformulation (T-NP.VOR) using the aminoethyl anisamide (AEAA)-functionalized, poly(ethylene glycol) (PEG)-decorated poly(lactic-co-glycolic acid) (PLGA) nano delivery carrier. In vitro, T‑NP.VOR significantly enhanced cellular uptake in CRC cells via Sigma‑1 receptor‑mediated uptake, leading to HDAC inhibition, cell cycle arrest, and apoptosis. In an orthotopic CRC mouse model, T‑NP.VOR markedly prolonged blood circulation and improved tumor distribution, resulting in significant tumor growth suppression and extended animal survival compared to free VOR and non‑targeted nanoformulation. Our findings confirm the PLGA-PEG-AEAA nanocarrier as a promising VOR delivery platform for CRC therapy. **Keywords:** Drug delivery; Nanoparticle; Targeted therapy; Vorinostat. Copyright © 2026 Elsevier B.V. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jianfeng Guo reports financial support was provided by Jilin Provincial Department of Science and Technology. Zhuo Yu reports financial support was provided by National Natural Science Foundation of China. Shulan Han reports financial support was provided by Jilin Provincial Department of Science and Technology. Shulan Han reports financial support was provided by National Natural Science Foundation of China. ## Similar articles * [ Co-Administration Of iRGD Enhances Tumor-Targeted Delivery And Anti-Tumor Effects Of Paclitaxel-Loaded PLGA Nanoparticles For Colorectal Cancer Treatment. ](https://pubmed.ncbi.nlm.nih.gov/31802868/) Zhong Y, Su T, Shi Q, Feng Y, Tao Z, Huang Q, Li L, Hu L, Li S, Tan H, Liu S, Yang H.Zhong Y, et al.Int J Nanomedicine. 2019 Nov 1;14:8543-8560. doi: 10.2147/IJN.S219820. eCollection 2019.Int J Nanomedicine. 2019.PMID: 31802868Free PMC article. * [ Synergistic anticancer effects of ABT-199 and Vorinostat encapsulated in PLGA nanoparticles: Formulation, characterization, and antiproliferative effects against colorectal cancer cells. ](https://pubmed.ncbi.nlm.nih.gov/41071780/) Abu Alsamen DR, Zakaraya ZZ, Abed A, Alsa'd AA, Alnajdawi MR.Abu Alsamen DR, et al.PLoS One. 2025 Oct 10;20(10):e0334427. doi: 10.1371/journal.pone.0334427. eCollection 2025.PLoS One. 2025.PMID: 41071780Free PMC article. * [ Preclinical activity of the rational combination of selumetinib (AZD6244) in combination with vorinostat in KRAS-mutant colorectal cancer models. ](https://pubmed.ncbi.nlm.nih.gov/22173548/) Morelli MP, Tentler JJ, Kulikowski GN, Tan AC, Bradshaw-Pierce EL, Pitts TM, Brown AM, Nallapareddy S, Arcaroli JJ, Serkova NJ, Hidalgo M, Ciardiello F, Eckhardt SG.Morelli MP, et al.Clin Cancer Res. 2012 Feb 15;18(4):1051-62. doi: 10.1158/1078-0432.CCR-11-1507. Epub 2011 Dec 15.Clin Cancer Res. 2012.PMID: 22173548Free PMC article. * [ Synergistic anticancer activity of combined histone deacetylase and proteasomal inhibitor-loaded zein nanoparticles in metastatic prostate cancers. ](https://pubmed.ncbi.nlm.nih.gov/27993720/) Thapa RK, Nguyen HT, Jeong JH, Shin BS, Ku SK, Choi HG, Yong CS, Kim JO.T
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