Engineering functional nanomaterials with high therapeutic efficacy and minimum side effects has increasingly become a promising strategy for cancer treatment. Herein, a reactive oxygen species (ROS) enhanced combination chemotherapy platform is designed via a biocompatible metal-polyphenol networks self-assembly process by encapsulating doxorubicin (DOX) and platinum prodrugs in nanoparticles. Both DOX and platinum drugs can activate nicotinamide adenine dinucleotide phosphate oxidases, generating superoxide radicals (O ). The superoxide dismutase-like activity of polyphenols can catalyze H O generation from O . Finally, the highly toxic HO free radicals are generated by a Fenton reaction. The ROS HO can synergize the chemotherapy by a cascade of bioreactions. Positron emission tomography imaging of Zr-labeled as-prepared DOX@Pt prodrug Fe nanoparticles (DPPF NPs) shows prolonged blood circulation and high tumor accumulation. Furthermore, the DPPF NPs can effectively inhibit tumor growth and reduce the side effects of anticancer drugs. This study establishes a novel ROS promoted synergistic nanomedicine platform for cancer therapy.

Subunit vaccines have been investigated in over 1000 clinical trials of cancer immunotherapy, but have shown limited efficacy. Nanovaccines may improve efficacy but have rarely been clinically translated. By conjugating molecular vaccines with Evans blue (EB) into albumin-binding vaccines (AlbiVax), here we develop clinically promising albumin/AlbiVax nanocomplexes that self-assemble in vivo from AlbiVax and endogenous albumin for efficient vaccine delivery and potent cancer immunotherapy. PET pharmacoimaging, super-resolution microscopies, and flow cytometry reveal almost 100-fold more efficient co-delivery of CpG and antigens (Ags) to lymph nodes (LNs) by albumin/AlbiVax than benchmark incomplete Freund’s adjuvant (IFA). Albumin/AlbiVax elicits ~10 times more frequent peripheral antigen-specific CD8+ cytotoxic T lymphocytes with immune memory than IFA-emulsifying vaccines. Albumin/AlbiVax specifically inhibits progression of established primary or metastatic EG7.OVA, B16F10, and MC38 tumors; combination with anti-PD-1 and/or Abraxane further potentiates immunotherapy and eradicates most MC38 tumors. Albumin/AlbiVax nanocomplexes are thus a robust platform for combination cancer immunotherapy.

Vaccines hold tremendous potential for cancer immunotherapy by treating the immune system. Subunit vaccines, including molecular adjuvants and cancer-associated antigens or cancer-specific neoantigens, can elicit potent antitumor immunity. However, subunit vaccines have shown limited clinical benefit in cancer patients, which is in part attributed to inefficient vaccine delivery. In this Perspective, we discuss vaccine delivery by synthetic nanoparticles or naturally derived nanoparticles for cancer immunotherapy. Nanovaccines can efficiently codeliver adjuvants and multiepitope antigens into lymphoid organs and into antigen-presenting cells, and the intracellular release of vaccine and cross-presentation of antigens can be fine-tuned via nanovaccine engineering. Aside from peptide antigens, antigen-encoding mRNA for cancer immunotherapy delivered by nanovaccine will also be discussed.