Bioresponsive immune-booster-based prodrug nanogel for cancer immunotherapy

Abstract

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo , via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

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

“…In recent years, studies have shown that Graphene (Deb et al., 2018 ), gold nanocages (Zhang et al., 2018b ), hydrogels (Ren et al., 2019 ; Wang et al., 2019b ; Abedi et al., 2021 ), prodrug nanogel (Ma et al., 2022 ), microspheres (Liu et al., 2017 ; Xu et al., 2021 ) and nanoclusters (He et al., 2020 ) can also be used for the co-delivery of natural active ingredients of and chemotherapy drugs. A summary of the researches of other nanocarriers used to co-deliver chemotherapy drugs and natural active ingredients is shown in Table 9 .…”

Bioengineered nanogels for cancer immunotherapy

“…7b). 114 After entering tumour cells, the GSH-responsive cross-linker would decompose in response to excessive GSH, releasing DOX and MAN. Meanwhile, DOX induced tumour ICD while MAN enhanced the sensitivity of tumour cells to chemotherapy, and the synergistic effect of the two drugs enhanced the infiltration of immune cells and restored exhausted TIM3 + PD-1 + T cells, and ultimately the survival time of mice was significantly prolonged.…”

One stone, many birds: Recent advances in functional nanogels for cancer nanotheranostics

“…DOX and mannose were co‐loaded to perform a combined chemo/immunotherapy. Specifically, DOX‐induced chemotherapy could cause tumor immunogenic cell death (ICD), manifesting the release of high‐mobility group box 1 (HMGB1) and the expose of calreticulin (CRT) on the cell membrane, resulting in an antitumor immune response to maximize the immune‐regulation effects from mannose (Ma, Yang, et al, 2021). Meanwhile, FIL was utilized to track the in vivo biodistribution and pharmacokinetics of the NGs.…”