The Application of Nanoparticles Targeting Cancer-Associated Fibroblasts

Abstract

Cancer-associated fibroblasts (CAF) are the most abundant stromal cells in the tumor microenvironment (TME), especially in solid tumors. It has been confirmed that it can not only interact with tumor cells to promote cancer progression and metastasis, but also affect the infiltration and function of immune cells to induce chemotherapy and immunotherapy resistance. So, targeting CAF has been considered an important method in cancer treatment. The rapid development of nanotechnology provides a good perspective to improve the efficiency of targeting CAF. At present, more and more researches have focused on the application of nanoparticles (NPs) in targeting CAF. These studies explored the effects of different types of NPs on CAF and the multifunctional nanomedicines that can eliminate CAF are able to enhance the EPR effect which facilitate the anti-tumor effect of themselves. There also exist amounts of studies focusing on using NPs to inhibit the activation and function of CAF to improve the therapeutic efficacy. The application of NPs targeting CAF needs to be based on an understanding of CAF biology. Therefore, in this review, we first summarized the latest progress of CAF biology, then discussed the types of CAF-targeting NPs and the main strategies in the current. The aim is to elucidate the application of NPs in targeting CAF and provide new insights for engineering nanomedicine to enhance immune response in cancer treatment.

Keywords:

• nanoparticles
• cancer therapy
• cancer-associated fibroblasts
• drug delivery
• cancer
• nanomedicine

Abbreviation

CAFs, cancer-associated fibroblasts; rCAFs, cancer-restraining CAF; myCAF, myofibroblastic CAFs; iCAF, inflammatory CAFs; apCAF, antigen-presenting CAFs; meCAF, metabolic CAFs; vCAF, vascular CAFs; EMT, epithelial-mesenchymal transition; TME, tumor microenvironment; TIME, tumor immune microenvironment; ECM, extracellular matrix; NPs, nanoparticles; NK, natural killer cells; DCs, dendritic cells; MDSCs, myeloid-derived suppressor cells; Tregs, regulatory T cells; VEGF, vascular endothelial growth factor; α-SMA, α-smooth muscle actin; MSCs, mesenchymal stem cells; LIF, Leukemia Inhibitory Factor; ICPs, immune checkpoint proteins; ICI, immune checkpoint inhibitor; PBMCs, peripheral blood mononuclear cells; TAMs, tumor-associated macrophages; BM, bone marrow; NSCLC, non-small cell lung cancer; IL, interleukin; ATAR, all-trans retinoic acid; PTT, photothermal therapy; PDT, photodynamic therapy; PEG, polyethylene glycol; FAP, fibroblast activation protein-α; TNC, tenascin C; SAB, salvianolic acid B; Frax, fraxinellone; LPD, lipid-coated protamine DNA; GNP, Gold nanoparticle; DTX, docetaxel; SPOIN, superparamagnetic iron oxide nanoparticle; PLGA, Poly(lactic-co-glycolic acid); EPR, enhanced permeability and retention effect; PSN38: PEG5K-P(MMESSN38)5K; PAMAM, the positive surface charge of cationic poly(amidoamine); RBC, red blood cells; ACF, acriflavine; PTX, paclitaxel; Nav, navitoclax; CPA, cyclopamine; DOX, doxorubicin; TPL, triptolide; NIR, near-infrared; sTRAIL, secretable TNF-related apoptosis-inducing ligand; DPPC, dipalmitoylphosphatidylcholine; APR, aprepitant; CUR, curcumin.

Data Sharing Statement

No data was used in the research and all related researches were referenced.

Acknowledgments

Our research was funded by the National Natural Science Foundation of China (No.82170779, No.82270804), 2019 Wuhan Yellow Crane Talent Program (Outstanding Young Talents), and the Tongji Hospital (HUST) Foundation for Excellent Young Scientist (No.2020YQ15).

Qiu Huang and Yue Ge are joint first authors for and contributed equally to this study. Zhiqiang Chen and Kun Tang are shared corresponding authors for this study.

Disclosure

The authors report no conflicts of interest in this work.