Supramolecular Tadalafil Nanovaccine for Cancer Immunotherapy by Alleviating Myeloid‐Derived Suppressor Cells and Heightening Immunogenicity

Abstract

Tumor‐induced immune suppression mediated by myeloid‐derived suppressor cells (MDSCs) and insufficient immunogenicity are two major factors for the poor overall response rate to the immune checkpoint blockade (ICB). Here, a tumor microenvironment responsive nanoprodrug (FIT nanoparticles) is presented for co‐delivering tadalafil (TAD) and indocyanine green (ICG) photosensitizer to simultaneously targeting intratumor MDSCs and amplifying tumor immunogenicity. The resulting nanoprodrug shows high drug loading (nearly 100%), tumor‐specific release, and robust therapeutic efficacy by virtue of promoting immunogenic cell death (ICD) induction and alleviation of MDSCs for augmenting the photothermal immunotherapy. In an in vivo colon tumor model, the released TAD in the tumor can effectively ameliorate MDSCs immunosuppressive activity, while the photosensitizer ICG is capable of inducing ICD to promote sufficient dendritic cells maturation and T cell infiltration. The results reported here may provide a superior candidate of adjuvants for strengthening immune response and ICB efficacy.

Nano-drug co-delivery system of natural active ingredients and chemotherapy drugs for cancer treatment: a review

“…Nevertheless, co-administration therapy may also have additive or synergistic effects resulted from interaction with several distinct targets at reduced administrated doses (Eftekhari et al., 2019 ). At present, there have been studies on nano-drug delivery system (NDDS) for the co-delivery of chemotherapy drugs with photosensitizers (Xiao et al., 2021 ; Zhang et al., 2021b ), and natural active ingredients.…”

Nanovaccines for Cancer Prevention and Immunotherapy: An Update Review

“…These nanovaccines can also be used in combination with other therapeutic approaches such as radiotherapy, immunotherapy, and chemotherapy, and by synergizing anti-tumor responses, they can eliminate the tumor, inhibit metastasis, and increase survival. According to this review of the latest studies on nanovaccines in cancer therapy, it is essential to comprehensively elucidate the mechanism of action of this nanovaccine [ 113 ]. Correspondingly, nanovaccine safety should be studied systematically.…”

“…Moreover, FIT + L could markedly suppress tumor growth without changing the studied mice’s weight. The authors suggested that these occurrences lead to DCs’ maturation and T cell activation, strengthening the anti-tumor immune response and immune checkpoint blockade efficacy [ 113 ].…”

Parental exposure of Tadalafil has beneficial effect on reflexive motor behaviors in mice offspring

“…In this regard, Duranti, Ceci, et al (2021) and Duranti, Maldini, et al (2021) demonstrate that Tadalafil improved oxidative capacity in C2C12 skeletal muscle cells by enhancing fat metabolism. As oxidation of the fatty acids needs more oxygen than glucose oxidation, elevated oxygen consumption in mitochondrial increases formation of the ROS (Zhang et al, 2021). Glutathione is the primary antioxidant responsible for maintaining a reduced intracellular microenvironment, and Tadalafil administration produced a redox perturbation by the altered GSH/GSSG ratio with no effect on TAS (Duranti, Ceci, et al, 2021; Duranti, Maldini, et al, 2021) which our findings were in agreement to this report.…”