Polyamino acid calcified nanohybrids induce immunogenic cell death for augmented chemotherapy and chemo-photodynamic synergistic therapy

Background: Monotherapy for cancer treatment is limited by unstable efficacy and uncontrollable toxic side effects, while the multifunctional nanoplatform with complex preparation process cannot avoid the potential toxicity of each functional component. Methods: We exploited tumor-specific activated polyamino acid calcified nanoparticles (CHC NPs) as new-type oxidative stress amplification of anticancer drugs via building a safe and biodegradable multifunctional nanoplatform. Giving priority to chemotherapy, and synergizing chemodynamic therapy (CDT) with photodynamic therapy (PDT), this strategy was to achieve enhanced chemotherapy, simultaneously inducing immunogenic cell death and inhibiting tumor cell invasion. Results: Based on amorphous calcium carbonate, pH-responsive nanocarrier was prepared with classical chemotherapeutic drug 10-hydroxycamplothecin (HCPT) and photosensitizer Chlorin e6 (Ce6) to realize multifunctional nanotheranostics. Conclusion: Inventive calcified nanohybrids, where topoisomerase inhibited by HCPT to prevent DNA synthesis, the generation of •OH induced via Fenton reaction, along with a large amount of 1O2 produced by Ce6, might be a promising strategy for anti-tumor combination therapy in clinical translation.