Microfluidic synthesis of manganese-alginate nanogels with self-supplying H2O2 capability for synergistic chemo/chemodynamic therapy and boosting anticancer immunity

As an interesting alternative to traditional cancer therapies, chemodynamic therapy (CDT) can kill cancer cells via the conversion of endogenous hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (.OH). However, the slow release of catalyst ions and insufficient H2O2 levels severely limit the performance of CDT. To address these issues, we explored the doxorubicin (DOX)-loaded manganese-alginate nanogel DOX@Mn-Alg with self-supplying H2O2 capability by using a microfluidic chip. After internalization into tumor cells, DOX@Mn-Alg quickly releases DOX in a pH-responsive manner. The released DOX can not only kill tumor cells directly but also improve Mn2+-mediated CDT by supplying H2O2 within the tumor cells. As a result, the DOX@Mn-Alg showed synergetic antitumor activity without causing distinct systemic toxicity, and also achieved T-1-weighted magnetic resonance imaging (MRI) enhancement for cancer diagnosis. Moreover, DOX@Mn-Alg treatment can promote DC maturation and increase tumor infiltration of CD8(+) T cells. It is believed that these Mn2+-chelating nanogels with the ability to self-supply H2O2 can provide additional strategy for synergetic CDT therapy and also exhibit a promising potential for cancer immunotherapy.