ArticleJournal of controlled release : official journal of the Controlled Release Society2022
Normalizing tumor microenvironment with nanomedicine and metronomic therapy to improve immunotherapy.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Analysis of multi-drug cancer nanomedicine.Nature nanotechnology · 2025Pooled it
- Multifunctional nanotherapeutics for tumor microenvironment modulation in solid tumor therapy.Discover nano · 2026Review
- A multiphysics computational model of focused ultrasound-enhanced drug delivery using temperature-sensitive liposomes.Biomechanics and modeling in mechanobiology · 2026Article
- Activatable nanoflytrap achieves synergistic "Capture-Block-Regulate" therapy of pancreatic ductal adenocarcinoma.Journal of nanobiotechnology · 2026Article
- Antiemesis Corticosteroids Potentiate Checkpoint Blockade Efficacy by Normalizing the Immune Microenvironment in Metastatic Murine Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Enhancing nanomedicine efficacy in KPC pancreatic tumors through ketotifen-mediated tumor microenvironment remodeling.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- HIFU postoperative hypoxia-activated metal-organic frameworks modulate the tumor microenvironment to augment immunotherapy.Journal of nanobiotechnology · 2026Article
- Deep learning prediction of chemo-immunotherapy response using tumor perfusion ultrasound images.Frontiers in artificial intelligence · 2026Article
- Sonopermeation combined with stroma normalization enables complete cure using nano-immunotherapy in murine breast tumors.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Article
- Mechanical forces inducing oxaliplatin resistance in pancreatic cancer can be targeted by autophagy inhibition.Communications biology · 2024Article
- Compressive stresses in cancer: characterization and implications for tumour progression and treatment.Nature reviews. Cancer · 2024Review
- A convolutional attention model for predicting response to chemo-immunotherapy from ultrasound elastography in mouse tumor models.Communications medicine · 2024Article
- Combined Metronomic Chemo-immunotherapy (CMCI) in Head and Neck Cancers-An Experience from a Developing Country.Indian journal of surgical oncology · 2024Article
- Canine Mammary Tumors: Classification, Biomarkers, Traditional and Personalized Therapies.International journal of molecular sciences · 2024Review
- Optimizing cancer therapy: a review of the multifaceted effects of metronomic chemotherapy.Frontiers in cell and developmental biology · 2024Review
- Development of an ultrasound-mediated nano-sized drug-delivery system for cancer treatment: from theory to experiment.Nanomedicine (London, England) · 2024Article
- Pirfenidone-Loaded Polymeric Micelles as an Effective Mechanotherapeutic to Potentiate Immunotherapy in Mouse Tumor Models.ACS nano · 2023Article
- Stimuli-sensitive nano-drug delivery with programmable size changes to enhance accumulation of therapeutic agents in tumors.Drug delivery · 2023Article
- Mitochondrial UQCC3 controls embryonic and tumor angiogenesis by regulating VEGF expression.iScience · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Nanomedicine offered hope for improving the treatment of cancer but the survival benefits of the clinically approved nanomedicines are modest in many cases when compared to conventional chemotherapy. Metronomic therapy, defined as the frequent, low dose administration of chemotherapeutics - is being tested in clinical trials as an alternative to the conventional maximum tolerated dose (MTD) chemotherapy schedule. Although metronomic chemotherapy has not been clinically approved yet, it has shown better survival than MTD in many preclinical studies. When beneficial, metronomic therapy seems to be associated with normalization of the tumor microenvironment including improvements in tumor perfusion, tissue oxygenation and drug delivery as well as activation of the immune system. Recent preclinical studies suggest that nanomedicines can cause similar changes in the tumor microenvironment. Here, by employing a mathematical framework, we show that both approaches can serve as normalization strategies to enhance treatment. Furthermore, employing murine breast and fibrosarcoma tumor models as well as ultrasound shear wave elastography and contrast-enhanced ultrasound, we provide evidence that the approved nanomedicine Doxil can induce normalization in a dose-dependent manner by improving tumor perfusion as a result of tissue softening. Finally, we show that pretreatment with a normalizing dose of Doxil can improve the efficacy of immune checkpoint inhibition.
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Registered trials
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.