Nanomedicine Strategies for Targeting Tumor Stroma

Abstract

The tumor stroma, or the microenvironment surrounding solid tumors, can significantly impact the effectiveness of cancer therapies. The tumor microenvironment is characterized by high interstitial pressure, a consequence of leaky vasculature, and dense stroma created by excessive deposition of various macromolecules such as collagen, fibronectin, and hyaluronic acid (HA). In addition, non-cancerous cells such as cancer-associated fibroblasts (CAFs) and the extracellular matrix (ECM) itself can promote tumor growth. In recent years, there has been increased interest in combining standard cancer treatments with stromal-targeting strategies or stromal modulators to improve therapeutic outcomes. Furthermore, the use of nanomedicine, which can improve the delivery and retention of drugs in the tumor, has been proposed to target the stroma. This review focuses on how different stromal components contribute to tumor progression and impede chemotherapeutic delivery. Additionally, this review highlights recent advancements in nanomedicine-based stromal modulation and discusses potential future directions for developing more effective stroma-targeted cancer therapies.

Strategies and Recent Advances on Improving Efficient Antitumor of Lenvatinib Based on Nanoparticle Delivery System

“…The internal triggers primarily exist in the tumor microenvironment, including specific enzymes, temperature, acid environment, etc. [98][99][100] For example, the tumor microenvironment always accompanied by high metabolic can generate higher local temperatures (3°C higher) and lower PH, promoting thermos-responsive and pH-responsive NDDS to release LVN into the tumor tissue. 74,101 Nonetheless, most of the internal triggers are hardly unique to diseased tissues and thus have low efficiency.…”

“…[115][116][117][118][119][120] The corresponding TME influences the effect of NDDS; however, nanotechnology has been developed to overcome the adverse factor from the TME and has been explored for reprogramming the tumor microenvironment. 100,121 The TME mainly includes three parts, ie, cellular components (all the non-cancerous host cells in the tumor, including fibroblasts, 122 endothelial cells, 123 and infiltrating immune cells), non-cellular components and non-cellular components of the TME (for example, an acidic environment, hypoxic conditions, and extracellular matrix). 100,121 Notably, TME remains an obstacle to achieving high efficiency for LVN; nonetheless, the unique environment can also be exploited to improve the targeting of the NDDS.…”

“…100,121 The TME mainly includes three parts, ie, cellular components (all the non-cancerous host cells in the tumor, including fibroblasts, 122 endothelial cells, 123 and infiltrating immune cells), non-cellular components and non-cellular components of the TME (for example, an acidic environment, hypoxic conditions, and extracellular matrix). 100,121 Notably, TME remains an obstacle to achieving high efficiency for LVN; nonetheless, the unique environment can also be exploited to improve the targeting of the NDDS. An important feature in the tumor intracellular conditions is a high glutathione (GSH) concentration, ie, 50-1000 times higher than that in extracellular microenvironments.…”

Nanoparticle-Mediated Drug Delivery Systems for Precision Targeting in Oncology

“…Furthermore, nanomedicine, which can improve the delivery and retention of drugs in the tumour, has been proposed to target the stroma [139].-Among the various TME modulators, stromal modulators (e.g., TGF-β inhibitors, hedgehog inhibitors, among others) have demonstrated more significant (>70%) tumour inhibition and have advanced to clinical trials for further evaluation [140]. Notably, several U.S. Food and Drug Administration (FDA) approved drugs, including losartan, GDC-0449 (vismodegib), and arsenic trioxide, initially indicated for hypertension, basal cell carcinoma, and refractory or relapsed acute promyelocytic leukaemia, respectively, have demonstrated improved anticancer efficacy when delivered in combination with TME modulators [141][142][143][144][145] In a small randomised clinical trial, the Hedgehog signalling inhibitor vismodegib, combined with gemcitabine and nab-paclitaxel, showed an improved survival rate in patients with pancreatic cancer.…”