Tumor-Associated Fibroblast-Targeting Nanoparticles for Enhancing Solid Tumor Therapy: Progress and Challenges

Abstract

Even though nanoparticle drug delivery systems (nanoDDSs) have improved antitumor efficacy by delivering more drugs to tumor sites compared to free and unencapsulated therapeutics, achieving satisfactory distribution and penetration of nanoDDSs inside solid tumors, especially in stromal fibrous tumors, remains challenging. As one of the most common stromal cells in solid tumors, tumor-associated fibroblasts (TAFs) not only promote tumor growth and metastasis but also reduce the drug delivery efficiency of nanoparticles through the tumor’s inherent physical and physiological barriers. Thus, TAFs have been emerging as attractive targets, and TAF-targeting nanotherapeutics have been extensively explored to enhance the tumor delivery efficiency and efficacy of various anticancer agents. The purpose of this Review is to opportunely summarize the underlying mechanisms of TAFs on obstructing nanoparticle-mediated drug delivery into tumors and discuss the current advances of a plethora of nanotherapeutic approaches for effectively targeting TAFs.

A CFH peptide-decorated liposomal oxymatrine inactivates cancer-associated fibroblasts of hepatocellular carcinoma through epithelial–mesenchymal transition reversion

“…CAFs are the most abundant stromal cells in the TME, which produce excessive collagen deposition to hinder intra-tumoral deep penetration of nanoparticles [ 24 ]. Herein, we investigated whether CFH/OM-L could inhibit the collagen secretion of CAFs in vitro.…”

Caenorhabditis elegans as a Prediction Platform for Nanotechnology-Based Strategies: Insights on Analytical Challenges

“…In this sense, model nanotoxicity studies based on non-mammalian alternatives to the C. elegans platform are rather promising for technological advances and regulatory scientific research for handling, labeling, testing toxicity, and evaluating the environmental impact of nanoparticles [ 39 ].…”

Resveratrol Loaded Liposomes Disrupt Cancer Associated Fibroblast Communications within the Tumor Microenvironment to Inhibit Colorectal Cancer Aggressiveness

“…The nanoparticle targeting CAF could reshape the TME or CAF and enhance drug delivery efficiency into tumor cells. Currently, several CAF-targeting nanoparticles have been reported that accomplished antitumor effects by eradicating CAF or reshaping the CAF functions [ 23 , 24 , 25 ].…”

“…RES had been used to interrupt crosstalk between CAF and cholangiocarcinoma cells and thus inhibit cell invasion of the cholangiocarcinoma cells [ 34 ]. Numerous studies have reported that resveratrol inhibits cell proliferation of cancer cells and tumor growth in vitro and in vivo in breast, colon, prostate, and lung cancers [ 24 , 35 , 36 ]. Unfortunately, clinical trials showed unsatisfactory results with no effect on tumor growth [ 28 ].…”