Table 3 Mechanism of action of nanomedicines targeting CAFs
Strategy | Nanomaterial | CAFs-targeting reagent | Therapeutic mechanism | Cancer type | Refs |
|---|---|---|---|---|---|
Inhibition CAF activation | MOF | Oxymatrine | Inhibition of CAF activation by reversing EMT and increasing the level of TILs | Liver cancer | [127] |
Liposome | Pirfenidone/DOX | Inhibition of CAFs by inhibiting pro-fibrotic cytokines and collagen synthesis | Breast cancer | [131] | |
Polymer NP | Curcumin | Baicalein reverses cellular fibrosis and reduces the expression of immunosuppressive factors by inhibiting the activation of the TGF-β/SMAD pathway and the TGF-β / MAPK pathways | Breast cancer | [119] | |
Polymer NP | Galunisertib | Galunisertib inhibited SMAD2/3 signaling by inhibiting phosphorylation and inducing immunosuppression | Colorectal | [9] | |
Polymeric micelles | Talabostat mesylate | Induction of ICD and promotion of TNF-α secretion and T-lymphocyte infiltration by inhibiting TGF-β secretion and downregulating α-SMA expression | Breast cancer | [110] | |
Nano Pue | Puerarin | Effective inhibition of SMAD2/3 phosphorylation and TGF-β/SMAD pro-fibrotic signaling by downregulating ROS in activated fibroblasts, thereby affecting immunosuppressive factors | Breast cancer | [208] | |
Polymeric micelles | Valsartan/DOX | Enhanced drug penetration and immune cell infiltration by decreasing type I collagen and α-SMA expression | Breast cancer | [138] | |
Nanogel | Oleanolic acid | Modulation of the ECM by attenuating fibrosis by inhibiting TGF-β/SMAD signaling and inactivating CAFs by reducing collagen | TNBC | [24] | |
Liposome | Silybin | Inactivation of CAFs by inhibiting NF-κB activation induces TME remodeling | Breast cancer | [25] | |
Liposome | Salvianolic acid B | Inhibiting TGF-β1/SMAD signaling and CAF activation, decreasing collagen deposition, alleviating the fibrotic environment, increasing the infiltration of CD8+ and CD4+ T cells into tumors, and increasing levels of Th1 cytokines while decreasing levels of Th2 cytokines | Breast cancer | [114] | |
Reprogramming/normalizing CAFs | Lipid NP | JQ1 | JQ1 normalizes CAFs by reducing the expression of genes associated with aberrant activation in CAFs, remodeling the ECM, and promoting immune cell infiltration | Pancreatic cancer | [133] |
Extracellular vesicles | Calcipotriol | Reprogramming CAFs into normal fibroblasts reduced the tumor ECM, effectively regulating T-cell infiltration into the tumor | Liver cancer | [207] | |
Mesoporous silica NP | Etinoic acid | Reversing CAF activation effectively overcame the physical barrier formed by deposited collagen and abnormal blood vessels, promoting the infiltration of immunostimulatory cells | Liver cancer | [209] | |
Liposome | Ginsenoside Rg3 | Reprograming activated CAFs into resting CAFs, attenuating the dense stromal barrier by inhibiting TGF-β secretion by tumor cells, modulating TGF-β/SMAD signaling, and reversing immunosuppression | Breast cancer | ||
Depletion/killing CAFs | Nanogel | S-Nitrosoglutathione | Activated CAFs are sensitive to NO, reducing TGF-β secretion by killing CAFs reduces the non-differentiation of monocytes recruited at the tumor site into M2-type macrophages | Breast cancer | [211] |
Polymer NP | Nintedanib/ABT-263 | Reducing the secretion of immunosuppressive factors, clearing and aging CAFs, and reshaping the tumor immunosuppressive microenvironment | Breast cancer | [198] | |
Cu(II) MOFs | Blebbistatin | Inducing apoptosis of CAFs by mediating the photogeneration of •OH to inhibit ECM production, synergize oxidative stress in tumors, and activate antitumor immune responses | Breast cancer | [125] | |
Au NP | DOX | Reduced CAFs by triggering the photothermal effect, remodeling the TME and increasing the number of NK cells in the tumor | Breast cancer | [124] | |
Polymeric micelles | Tranilast/DOX | Optimises TME mechanoregulation and tumor perfusion by reducing fibrotic conductance in CAFs. Durable long-term antitumor response and immune memory in combination with chemotherapeutic agents | Breast cancer | [108] | |
FeCo-ZIF | Telmisartan | Enhances drug penetration into tumors and infiltration of cytotoxic T lymphocytes by specifically killing CAFs, destroying ECM, and delaying CXCL12 secretion | Breast cancer | [128] | |
Lipid NP | Paclitaxel/PFK15 | Reduced lactate production of lactate and reduced production of immunosuppressive factors by blocking the metabolic support of CAFs to cancer cells | Breast cancer | [129] |