---
title: "Hydrogel strategies to remodel the tumor microenvironment for improved cancer immunotherapy"
id: "pubmed-42562132"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42562132"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42562132/"
doi: "10.1016/j.ijpharm.2026.127286"
published_at: "2026-09-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Hydrogel strategies to remodel the tumor microenvironment for improved cancer immunotherapy
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42562132
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42562132/)
- **DOI:** [10.1016/j.ijpharm.2026.127286](https://doi.org/10.1016%2Fj.ijpharm.2026.127286)
- **Published At:** 2026-09-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Cancer remains a leading cause of death worldwide and existing therapies (chemotherapy, surgery, radiotherapy, immunotherapy) are limited by an antagonistic **tumor microenvironment** (TME). - Drug delivery systems at nano-, micro-, and macro-scales can remodel the TME by improving pharmacokinetics and coordinating multiple therapeutic modalities. - **Hydrogels** are particularly promising for TME modulation because of their **tunable microstructures**, high drug loading capacity, and scalable manufacturing. - Recent work has focused on hydrogel-based, drug-loaded platforms to modulate the TME specifically for **tumor immunotherapy**. - Strategies target conversion of immunologically distinct tumor phenotypes: **hot tumors** (inflamed), **cold tumors** (non-inflamed), including **immune-desert** and **immune-excluded** phenotypes. - Remodeling approaches aim to enhance immune infiltration, overcome immune suppression, and coordinate local delivery of agents to improve efficacy and safety. - The review summarizes underlying immunological mechanisms by which hydrogels modulate the TME, including effects on immune cell recruitment and local pharmacokinetics. - Key translational challenges remain for hydrogel-based TME modulation, such as clinical translation barriers, manufacturing, safety, and integration with current therapies. - The authors highlight the potential of hydrogels to provide coordinated, local, and sustained modulation of the TME to augment anti-tumor treatments and immunotherapies.
## Clinical Analysis & Structured Key Points
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Epub 2026 Aug 6. # Hydrogel-dependent strategies to modulate the tumor microenvironment for improved anti-tumor treatment [Ni Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+N&cauthor_id=42562132)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#full-view-affiliation-1 "National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Yanxin Zhou](https://pubmed.ncbi.nlm.nih.gov/?term=Zhou+Y&cauthor_id=42562132)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#full-view-affiliation-1 "National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Yang Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+Y&cauthor_id=42562132)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#full-view-affiliation-2 "National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China."), [Xiaohan Yi](https://pubmed.ncbi.nlm.nih.gov/?term=Yi+X&cauthor_id=42562132)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#full-view-affiliation-1 "National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Yingpei Mu](https://pubmed.ncbi.nlm.nih.gov/?term=Mu+Y&cauthor_id=42562132)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#full-view-affiliation-1 "National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Fengyun Sun](https://pubmed.ncbi.nlm.nih.gov/?term=Sun+F&cauthor_id=42562132)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#full-view-affiliation-3 "College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Mintao Han](https://pubmed.ncbi.nlm.nih.gov/?term=Han+M&cauthor_id=42562132)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#full-view-affiliation-3 "College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Chunmei Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+C&cauthor_id=42562132)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#full-view-affiliation-3 "College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Maoli Yin](https://pubmed.ncbi.nlm.nih.gov/?term=Yin+M&cauthor_id=42562132)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#full-view-affiliation-4 "School of Textile and Garment, Anhui Polytechnic University, Wuhu, Anhui 241000, China."), [Huan Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+H&cauthor_id=42562132)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#full-view-affiliation-5 "Department of Clinical Laboratory Medicine, The General Hospital of Xizang Military Command, Lhasa 850000, China."), [Xuan Han](https://pubmed.ncbi.nlm.nih.gov/?term=Han+X&cauthor_id=42562132)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#full-view-affiliation-6 "School of Integrated Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China. Electronic address: hanxuan@njucm.edu.cn."), [Bo Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+B&cauthor_id=42562132)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#full-view-affiliation-7 "Department of Biopharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu, China. Electronic address: wangbo@cpu.edu.cn."), [Jing Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+J&cauthor_id=42562132)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#full-view-affiliation-8 "National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: jingchen3236@njucm.edu.cn.") Affiliations Expand ### Affiliations * 1 National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. * 2 National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China. * 3 College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. * 4 School of Textile and Garment, Anhui Polytechnic University, Wuhu, Anhui 241000, China. * 5 Department of Clinical Laboratory Medicine, The General Hospital of Xizang Military Command, Lhasa 850000, China. * 6 School of Integrated Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China. Electronic address: hanxuan@njucm.edu.cn. * 7 Department of Biopharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu, China. Electronic address: wangbo@cpu.edu.cn. * 8 National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: jingchen3236@njucm.edu.cn. * PMID: **42562132** * DOI: [ 10.1016/j.ijpharm.2026.127286 ](https://doi.org/10.1016/j.ijpharm.2026.127286) Item in Clipboard Review # Hydrogel-dependent strategies to modulate the tumor microenvironment for improved anti-tumor treatment Ni 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/42562132/) . 2026 Sep 5:702:127286. doi: 10.1016/j.ijpharm.2026.127286. Epub 2026 Aug 6. ### Authors [Ni Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+N&cauthor_id=42562132)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#short-view-affiliation-1 "National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Yanxin Zhou](https://pubmed.ncbi.nlm.nih.gov/?term=Zhou+Y&cauthor_id=42562132)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#short-view-affiliation-1 "National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Yang Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+Y&cauthor_id=42562132)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#short-view-affiliation-2 "National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China."), [Xiaohan Yi](https://pubmed.ncbi.nlm.nih.gov/?term=Yi+X&cauthor_id=42562132)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#short-view-affiliation-1 "National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Yingpei Mu](https://pubmed.ncbi.nlm.nih.gov/?term=Mu+Y&cauthor_id=42562132)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#short-view-affiliation-1 "National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Fengyun Sun](https://pubmed.ncbi.nlm.nih.gov/?term=Sun+F&cauthor_id=42562132)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#short-view-affiliation-3 "College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Mintao Han](https://pubmed.ncbi.nlm.nih.gov/?term=Han+M&cauthor_id=42562132)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#short-view-affiliation-3 "College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Chunmei Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+C&cauthor_id=42562132)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#short-view-affiliation-3 "College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China."), [Maoli Yin](https://pubmed.ncbi.nlm.nih.gov/?term=Yin+M&cauthor_id=42562132)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#short-view-affiliation-4 "School of Textile and Garment, Anhui Polytechnic University, Wuhu, Anhui 241000, China."), [Huan Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+H&cauthor_id=42562132)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#short-view-affiliation-5 "Department of Clinical Laboratory Medicine, The General Hospital of Xizang Military Command, Lhasa 850000, China."), [Xuan Han](https://pubmed.ncbi.nlm.nih.gov/?term=Han+X&cauthor_id=42562132)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#short-view-affiliation-6 "School of Integrated Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China. Electronic address: hanxuan@njucm.edu.cn."), [Bo Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+B&cauthor_id=42562132)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#short-view-affiliation-7 "Department of Biopharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu, China. Electronic address: wangbo@cpu.edu.cn."), [Jing Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+J&cauthor_id=42562132)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42562132/#short-view-affiliation-8 "National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: jingchen3236@njucm.edu.cn.") ### Affiliations * 1 National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. * 2 National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China. * 3 College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. * 4 School of Textile and Garment, Anhui Polytechnic University, Wuhu, Anhui 241000, China. * 5 Department of Clinical Laboratory Medicine, The General Hospital of Xizang Military Command, Lhasa 850000, China. * 6 School of Integrated Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China. Electronic address: hanxuan@njucm.edu.cn. * 7 Department of Biopharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu, China. Electronic address: wangbo@cpu.edu.cn. * 8 National Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: jingchen3236@njucm.edu.cn. * PMID: **42562132** * DOI: [ 10.1016/j.ijpharm.2026.127286 ](https://doi.org/10.1016/j.ijpharm.2026.127286) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Cancer remains a leading cause of death worldwide, and effective therapies are still urgently needed. Although chemotherapy, surgery, radiotherapy, and immunotherapy have advanced cancer treatment, their efficacy and safety are often limited by the antagonistic tumor microenvironment (TME). Drug delivery systems across nano-, micro-, and macroscale dimensions offer opportunities to remodel the TME by improving pharmacokinetics and coordinating therapeutic modalities. Among them, hydrogels are particularly attractive owing to their tunable microstructures, high loading capacity, and manufacturing scalability. This review summarizes recent advances in drug-loaded hydrogels for TME modulation in tumor immunotherapy, focusing on strategies for remodeling hot and cold tumors, including immune-desert and immune-excluded phenotypes, their underlying immunological mechanisms, and key translational challenges. **Keywords:** Hydrogel; Immunotherapy; Tumor microenvironment. Copyright © 2026 Elsevier B.V. All rights reserved. [PubMed Disclaimer](https://pubmed.
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