Sequential MR Image‐Guided Local Immune Checkpoint Blockade Cancer Immunotherapy Using Ferumoxytol Capped Ultralarge Pore Mesoporous Silica Carriers after Standard Chemotherapy

Abstract

Herein, ferumoxytol (Fer) capped antiprogrammed cell death‐ligand 1 (PD‐L1) antibodies (aPD‐L1) loaded ultralarge pore mesoporous silica nanoparticles (Fer‐ICB‐UPMSNPs) are formulated for a sequential magnetic resonance (MR) image guided local immunotherapy after cabazitaxel (Cbz) chemotherapy for the treatment of prostate cancer (PC). The highly porous framework of UPMSNP provides a large capacity for aPD‐L1. Fer capping of the pores extends the period of aPD‐L1 release and provides MR visibility of the aPD‐L1 loaded UPMSNP. As‐chosen Cbz chemotherapy prior to the local immunotherapy induces strong immunogenic cell death, dendritic cell maturation, and upregulation of PD‐L1 of tumor cells. Finally, tumor growth inhibition of sequential MR image‐guided local delivery of Fer‐ICB‐UPMSNPs and a tumor specific adoptive immune reaction are demonstrated in the pretreated Tramp C1 PC mouse model with Cbz chemotherapy. The tumor suppression is superior to those obtained with systemic ICB treatment after Cbz, only Fer‐ICB‐UPMSNP or only Cbz. As a proof‐of concept, MR image‐guided local ICB immunotherapy using Fer‐ICB‐UPMSNPs after chemotherapy suggests a new perspective of translational local immunotherapy for patients who are treated with standard chemotherapies.

An Update on Mesoporous Silica Nanoparticle Applications in Nanomedicine

“…This study supports the feasibility of MSN-based carriers for the delivery of GSK3 inhibitors in anti-cancer immunotherapy. Besides, Choi et al formulated an FDA-approved iron oxide nanoparticles ferumoxytol (Fer)-capped immune checkpoint blockade (PD-L1 antibody)-loaded ultra-large pore MSNs (ICB-UPMSNPs) for a sequential MRI-guided local immunotherapy in prostate cancer after cabazitaxel chemotherapy [ 420 ]. The highly porous framework of ICB-UPMSNPs allowed the high loading of PD-L1 antibodies.…”

Magnetic Nanostructures as Emerging Therapeutic Tools to Boost Anti-Tumour Immunity

“…Surface modification has been also exploited to facilitate the loading of immunomodulators that can activate and/or boost the immune responses in patients [ 57 , 58 ]. The most common surface modification strategies, such as ligand exchange, porous silica, phospholipid, and polymer coating, have been extensively explored to facilitate loading of various immunotherapeutics, including TLR agonists and monoclonal antibodies onto MNPs through non-covalent or covalent interactions, taking advantage of the properties associated with the coating material (e.g., large pore size of the porous silica shell and large number of reactive functional groups of polymers) ( Figure 3 ) [ 57 , 58 , 59 , 60 ].…”

“…A range of surface chemistry strategies also has been explored to facilitate multiple-drug loading. In this regard, the highly porous structures of mesoporous silica-coated ferumoxytol nanoparticles were capable to load both a checkpoint inhibitor (anti-PD-L1 antibody) and chemotherapeutic drug (cabazitaxel) for achieving an anti-tumoural synergistic effect against prostate cancer [ 57 ]. Likewise, surface modification of MNPs with a lipid shell enabled the co-encapsulation of the α-helix-antigen fusogenic peptide (α-AP) with indocyanine green (ICG), an imaging agent, leading to the development of a theragnostic nanoplatform (α-AP-fmNP) [ 58 ].…”

Multifunctional Nanocarriers‐Mediated Synergistic Combination of Immune Checkpoint Inhibitor Cancer Immunotherapy and Interventional Oncology Therapy

“…Reproduced with permission. [ 82 ] Copyright 2019, Wiley‐VCH. c) i) aPD–L1‐loaded S–AuNC for synergistic combination of RT and ICI cancer immunotherapy of low immunogenic PC.…”