Table 4.
NDDS for modulating the effects of CAFs on tumor cells and the ECM.
| Targeting mechanism | Effect on CAFs | Loaded drug | Delivery system and typical feature | Tumor metastasis model | Mechanism of anti-metastasis | Effectiveness of anti-metastasis | Ref. |
|---|---|---|---|---|---|---|---|
| EPR effect | Reduce the secretion of CXCL12 and IL-6 | RES | Nanoparticles; prepared by single emulsion solvent evaporation method | Oral cancer metastasis in kidney, liver, brain, neck lymph nodes and lung | Inhibit the ECM remodeling of CAFs and reduce EMT induced by CAFs | 75% metastasis reduction compared to the control group | 218 |
| Affinity of AEAA and sigma | Reduce the secretion of TGF-β, CXCL12, and IL-6 | MIT, CEL | Nanoparticles; TME-responsive (pH and GSH) |
Melanoma metastasis in liver and lung | Inhibit the ECM remodeling of CAFs | – | 219 |
| Affinity of MMP-2 and TME, spatial targeting of CAFs. | Reduce the secretion of Wnt16 | GA, DGL-GEM | Nanoparticles; size-switchable, MMP-2-sensitive | Breast cancer metastasis in major organs | Inhibit the ECM remodeling of CAFs | – | 221 |
| Affinity of MMP-2 and TME | QUE, PTX | Liposomes; MMP-sensitive, sequential delivery, dual-targeting, hybrid micelle-in-liposome |
Breast cancer lung metastasis | Inhibit the ECM remodeling of CAFs | – | 222 | |
| Homologous targeting | Reduce the secretion of lactate | PFK15, PTX | Nanoparticles; dual-targeting, Homologous targeting, biomimetic |
Breast cancer metastasis | Inhibit the ECM remodeling of CAFs | – | 223 |
| Intratumoral administration | Inhibit the synthesis and secretion of collagen | LOS,DOX | Hydrogel, liposomes; self-assembly | Breast cancer lung metastasis | Inhibit the ECM remodeling of CAFs and reduce EMT induced by CAFs | 80% metastasis reduction compared to the control group | 227 |
| Intratumoral administration | LOS, TEL | Fiber fragments; sequential drug release | Breast cancer lung metastasis | Inhibit the ECM remodeling of CAFs | 90% metastasis reduction compared to the control group | 228 | |
| Affinity of AEAA and sigma | LOS, DOX, ferric ions | Carbon dots; CAFs-responsive; sequential and spatiotemporal release |
Breast cancer lung metastasis | Inhibit the ECM remodeling of CAFs | 100% metastasis reduction compared to the control group | 230 | |
| Specific drug release with esterase-responsive properties | TPL | Micelles; esterase-responsive property | Gastric cancer metastasis in the peritoneal cavity | Inhibit the ECM remodeling of CAFs | 90% metastasis reduction compared to the control group | 231 | |
| Specific drug release with CTSB-responsive | DAS, epirubicin | Nanoparticles; sequential delivery, cathepsin B-responsive, pH-responsive |
Breast cancer lung metastasis | Inhibit the ECM remodeling of CAFs | – | 233 | |
| Homologous targeting | Inhibit the secretion of MMP-14 | ART | Nanoparticles; homologous targeting, biomimetic | Breast cancer metastasis | Inhibit the ECM remodeling of CAFs | – | 234 |
‒, not applicable. CAFs, cancer-associated fibroblasts; ECM, extracellular matrix; EPR, enhanced permeability and retention; CXCL12, C-X-C motif chemokine ligand 12; IL-6, interleukin- 6; RES, resveratrol; EMT, epithelial–mesenchymal transition; AEAA, aminoethyl anisamide; TGF-β, transforming growth factor-beta; MIT, mitoxantrone; CEL, celastrol; TME, tumor microenvironment; GSH,Glutathione; MMP-2, matrix metallopeptidase 2; Wnt16, wnt family member 16; GA, glycyrrhetinic acid; DGL-GEM, dendrigraft poly-l-lysine-gemcitabin; QUE, quercetin; PTX, paclitaxel; LOS, losartan; DOX, doxorubicin; TEL, telmisartan; TPL, triptolide; CTSB, cathepsin B; DAS, Dasatinib; ART, artesunate.