Interestingly, benefiting from the biodegraded debris, it was found that CD@MSN-mediated PTT can synergistically achieve immune-mediated inhibition of tumor metastasis via stimulating the proliferation and activation of natural killer cells and macrophages with simultaneously up-regulating the secretion of corresponding cytokines (IFN-γ and Granzyme B).
In immunocompetent mouse 4T1 breast tumor model, intratumoral delivery of rAd.sT inhibited both tumor growth and lung metastases. rAd.sT downregulated the expression of several transforming growth factor β (TGFβ) target genes involved in tumor growth and metastases, inhibited Th2 cytokine expression, and induced Th1 cytokines and chemokines, and granzyme B and perforin expression. rAd.sT treatment also increased the percentage of CD8<sup>+</sup> T lymphocytes, promoted the generation of CD4<sup>+</sup> T memory cells, reduced regulatory T lymphocytes (Tregs), and reduced bone marrow-derived suppressor cells.