Metal–Phenolic Network-Encapsulated Nanovaccine with pH and Reduction Dual Responsiveness for Enhanced Cancer Immunotherapy

Abstract

Cancer nanovaccines have been widely explored to enhance immunotherapy efficiency, in which the significant irritation of antigen-specific cytotoxic T cells (CTLs) is the critical point. In this study, we developed a pH and reduction dualsensitive nanovaccine (PMSN@OVA-MPN) composed of two parts. The inner part was made up of polyethyleneimine (PEI)modified mesoporous silica nanoparticles (MSNs) loaded with model antigen ovalbumin (OVA) and the outer part was made up of disulfide bond-involved metal−phenolic networks (MPNs) as a protective corona. In vitro release experiments proved that PMSN@OVA-MPN could intelligently release OVA in the presence of reductive glutathione, but not in neutral phosphatebuffered saline (PBS). Moreover, in vitro cell assays indicated that the nanovaccine promoted not only the OVA uptake efficiency by DC2.4 cells but also antigen lysosome escape due to the proton sponge effect of PEI. Furthermore, in vivo animal experiments indicated that PMSN@OVA-MPN induced a large tumor-specific cellular immune response so as to effectively inhibit the growth of an existing tumor. Finally, the immune memory effect caused by the nanovaccine afforded conspicuous prophylaxis efficacy in neonatal tumors. Hence, the multifunctional vaccine delivery system prepared in this work exhibits a great application potential in cancer immunotherapy and offers a platform for the development of nanovaccines.

Nanostructured particles assembled from natural building blocks for advanced therapies

“…456 The immune response can be further enhanced by the presentation of antigens generated by adjuvant therapy. 455,457 For instance, PDA-based nanoparticles can function as PTT agents coupled with the co-delivery of immunomodulatory payloads. 458 (3) Particle-based gene therapy primarily focuses on the targeted delivery of nucleic acids into cells for the purpose of altering the course of a medical condition or disease through the modulation of gene regulation and expression processes.…”

Mesoporous Silica Materials as an Emerging Tool for Cancer Immunotherapy

“…In parallel, Zhou et al engineered a multifunctional cancer nanovaccine composed of a MSN functionalized with polyethyleneimine (PEI) (PMSN), loaded with the model antigen OVA and coated by disulfide-bond-involved metal-phenolic networks (MPN) (PMSN@OVA-MPN) (Figure 2). [85] Significant OVA delivery (60% and 80% in 10 min, respectively), and efficient lysosome escape due to the PEI-triggered proton sponge effect, thus, allowed cytosolic OVA release and the subsequent antigen cross-presentation by MHC-I to be achieved. For antitumor studies, mice (C57BL/6) were inoculated with E.G7-OVA lymphoma cells by subcutaneous injection in the right flank before immunization with PMSN@OVA-MPN.…”

Recent advances in porous nanomaterials-based drug delivery systems for cancer immunotherapy

“…In another work, pH and reduction dual responsive MSNs were designed to deliver OVA (PMSN@OVA-MPN) and release them inside tumor cells. PMSN@OVA-MPN elevated OVA internalization by DC2.4 cells as well as the release of antigens from the lysosome, eliciting stronger cellular immune responses for more effective inhibition of tumor progression [ 58 ]. Mono-dispersed mesostructured hollow carbon spheres are also used for OVA delivery and demonstrated good drug-loading efficacy, sustained-release behavior, enhanced cellular uptake and promoted APCs maturation [ 59 ].…”

“…3 Schematic illustration of various inorganic, organic, and hybrid porous nanomaterials (PNMs) for tumor therapy. Inorganic PNMs include: H-MnO 2 -PEG [ 73 ], OX/IND-MSNP [ 55 ], PMSN@OVA-MPN [ 58 ], CuS@mSiO 2 -PFP-PEG [ 75 ]; organic PNMs include: COF@ICG@OVA 109 ], COF-609 + αCD47 [ 80 ]; hybrid PNMs include: Hf-DBP/αCD47 [ 98 ], IDOi@Hf-TBC [ 4 ], MOF-S-S-OVA@CpG [ 100 ], NV-ZIF [ 94 ], ZANPs [ 99 ], Hf12-DBA [ 96 ]. PNMs can achieve the combination of cancer immunotherapy with PDT, PTT, CT, and RT for better cancer treatment outcomes …”