*3.2.2 Targeted modulation of T cells*

Kosmides et al. fabricated an "immunoswitch" iron-dextran nanoparticle coated with two different antibodies which can simultaneously block the PD-L1 inhibitory signal and activate T cells through 4-1BB co-stimulatory pathway [32]. The intratumoral treatment with immunoswitch NPs suppressed tumor growth and prolonged survival time compared with direct co-injection of free antibodies in various tumor models-bearing mice. In addition, regulatory T (Treg) cells can induce immunosuppressive TME which is a major obstacle for cancer immunotherapy. In an exemplified study, Ou et al. constructed imatinib (IMT)-loaded, tLyp1 peptide-decorated hybrid NPs (IMT-loaded tLyp1-hNP) which exhibited good stability and effective targeting ability to neuropilin-1 (Nrp1) overexpressing Tregs in TME [33]. IMT was applied to reduce the proportion of Treg cells by blocking STAT3 and STAT5 signaling. The IMT-loaded tLyp1-hNP showed higher cellular uptake efficiency for Treg cells and boost the effect of imatinib in inhibiting Tregs-mediated suppression. The combination treatment of α-CTLA-4-based ICT and IMT-loaded tLyp-hNPs increased tumorinfiltrating CD8+ T cells and extended survival of B16BL/6 tumor-bearing mice, suggesting that reducing Tregs mediated by targeted IMT-loaded tLyp-hNPs enabled a synergistic effect with ICT.
