Nanomedicines Targeting Metabolism in the Tumor Microenvironment

Abstract

Cancer cells reprogram their metabolism to meet their growing demand for bioenergy and biosynthesis. The metabolic profile of cancer cells usually includes dysregulation of main nutritional metabolic pathways and the production of metabolites, which leads to a tumor microenvironment (TME) having the characteristics of acidity, hypoxic, and/or nutrient depletion. Therapies targeting metabolism have become an active and revolutionary research topic for anti-cancer drug development. The differential metabolic vulnerabilities between tumor cells and other cells within TME provide nanotechnology a therapeutic window of anti-cancer. In this review, we present the metabolic characteristics of intrinsic cancer cells and TME and summarize representative strategies of nanoparticles in metabolism-regulating anti-cancer therapy. Then, we put forward the challenges and opportunities of using nanoparticles in this emerging field.

Harnessing Immune Checkpoint Inhibitors Against Gastric Cancer: Charting the Course to Expanded Therapeutic Benefit

“…Studies indicating specific bacterial species' enrichment in treatment responders suggest that microbiome modulation could be a novel strategy to augment immunotherapy success 143 . Exploring metabolic pathway targeting within the tumor microenvironment emerges as another strategy to boost immunotherapy efficacy by fostering conditions that support antitumor immunity [144][145][146] . Collaborative efforts across research, clinical, and bioinformatics disciplines are crucial for harnessing big data's full potential in advancing predictive biomarker research toward clinical application.…”

Patient-derived xenografts or organoids in the discovery of traditional and self-assembled drug for tumor immunotherapy

“…Currently, TME is regarded as the presentation of non-tumor cells and their components in tumors, including the protein molecules produced and released by them (8). Furthermore, the metabolic disorders of TME cells result in the consumption of nutrients, acidification of environmental pH, hypoxia, and the production of regulatory metabolites, thus influencing the immune response to tumors as well as the overexpression of immune checkpoint molecules and tumor metastasis (9)(10)(11). The abortive phenomenon of various tumor therapy drugs in previous preclinical and clinical trials has been explained by the discovery of TME.…”

Targeted Delivery of Anticancer Therapeutics with Polymers by Harnessing Tumor Microenvironment Acidity

“…However, cells in the TME mainly produce adenosine triphosphate (ATP) through glycolysis, even under aerobic conditions, which is known as aerobic glycolysis or the Warburg effect. Furthermore, instead of using glycolytic coupling with the tricarboxylic acid (TCA) cycle to produce more energy and intermediates, cells in the TME convert around 90% of glycolytic pyruvate into lactic acid that is secreted into the extracellular environment, leading to an acidic TME. ,, According to the “seed and soil” hypothesis, the TME can promote tumor growth and proliferation by maintaining signal transduction and resisting cell death . Moreover, the TME plays a crucial role in cancer metastasis. , Lower pH levels in the TME (around 6.5–6.9) compared to the normal cell microenvironment (approximately 7.2–7.4) provide an intrinsic trigger for targeted delivery of anticancer therapeutics to TME. ,, The acidity difference provides carriers with the ability to target tumor tissue.…”

“…14,15 Lower pH levels in the TME (around 6.5−6.9) compared to the normal cell microenvironment (approximately 7.2−7.4) provide an intrinsic trigger for targeted delivery of anticancer therapeutics to TME. 17,22,24 The acidity difference provides carriers with the ability to target tumor tissue. They remain stable in the normal cell microenvironment but change their physiochemical properties, such as shrinkage and protective layer removal, once they reach the acidic TME.…”