Drug-Free Mesoporous\nSilica Nanoparticles Enable Suppression\nof Cancer Metastasis and Confer Survival Advantages to Mice with Tumor\nXenografts

Despite advancements in nanomedicine for drug delivery,\nmany drug-loaded\nnanoparticles reduce tumor sizes but often fail to prevent metastasis.\nMesoporous silica nanoparticles (MSNs) have attracted attention as\npromising nanocarriers. Here, we demonstrated that MSN-PEG/TA 25,\nwith proper surface modifications, exhibited unique antimetastatic\nproperties. In vivo studies showed that overall tumor metastasis decreased\nin 4T1 xenografts mice treated with MSN-PEG/TA 25 with a notable reduction\nin lung tumor metastasis. In vitro assays, including wound-healing,\nBoyden chamber, tube-formation, and real-time cell analyses, showed\nthat MSN-PEG/TA 25 could modulate cell migration of 4T1 breast cancer\ncells and interrupt tube formation by human umbilical vein endothelial\ncells (HUVECs), key factors in suppressing cancer metastasis. The\nsynergistic effect of MSN-PEG/TA 25 combined with liposomal-encapsulated\ndoxorubicin (Lipo-Dox) significantly boosted mouse survival rates,\noutperforming Lipo-Dox monotherapy. We attributed the improved survival\nto the antimetastatic capabilities of MSN-PEG/TA 25. Moreover, Dox-loaded\nMSN-PEG/TA 25 suppressed primary tumors while retaining the antimetastatic\neffect, thereby enhancing therapeutic outcomes and overall survival.\nWestern blot and qPCR analyses revealed that MSN-PEG/TA 25 interfered\nwith the phosphorylation of ERK, FAK, and paxillin, thus impacting\nfocal adhesion turnover and inhibiting cell motility. Our findings\nsuggest that drug-free MSN-PEG/TA 25 is highly efficient for cancer\ntreatment via suppressing metastatic activity and angiogenesis.