Radiation
therapy (RT)-mediated tumor immunogenicity offers an
opportunity for synergistic combination RT and immunotherapy. One
of the challenges in the clinic is to attain the optimum efficacy
of combination RT and immunotherapy with minimized overlapping toxicities.
Here, to achieve synergistic therapeutic efficacy of combinational
RT and anti-programmed death ligand 1 (aPD-L1) immunotherapy, RT-responsive
splintery snowflake-like Au nanocarriers (S-AuNC) were synthesized
with a method for hierarchical bimetallic supra-nanostructures. Primary
Au nanocrystals interconnected with Ag nanocrystals in S-AuNC showed
RT-responsive structural deformation resulting in RT-triggered release
of cargo aPD-LI in S-AuNC. The local combination of RT and aPD-L1
loaded S-AuNC significantly enhanced the immunogenic cell death for
tumor microenvironment conversion. RT-triggered local aPD-L1 release
allowed a controlled spatiotemporal combination RT and aPD-L1 immunotherapy
resulting in a synergistic anticancer adaptive immune response with
minimized systemic immune-related adverse effects.
Natural
killer (NK) cell-based immunotherapy has been considered
a promising cell-based cancer treatment strategy with low side effects
for early tumors and metastasis. However, the therapeutic efficacy
is generally low in established solid tumors. Ex vivo activation of NK cells with exogenous cytokines is often essential
but ineffective to generate high doses of functional NK cells for
cancer treatment. Image-guided local delivery of NK cells is also
suggested for the therapy. However, there is a lack of noninvasive
tools for monitoring NK cells. Herein, magnetic nanocomplexes are
fabricated with clinically available materials (hyaluronic acid, protamine,
and ferumoxytol; HAPF) for labeling NK cells. The prepared HAPF–nanocomplexes
effectively attach to the NK cells (HAPF-NK). An exogenous magnetic
field application effectively achieves magneto-activation of NK cells,
promoting the generation and secretion of lytic granules of NK cells.
The magneto-activated HAPF-NK cells also allow an MR image-guided
NK cell therapy to treat hepatocellular carcinoma (HCC) solid tumors
via transcatheter intra-arterial infusion. Suppressed tumor growth
after the treatment of IA infused magneto-activated NK cells demonstrated
a potential enhanced therapeutic efficacy of image guided local delivery
of magneto-activated HAPF-NK cells. Given the potential challenges
of NK cell cancer immunotherapy against established solid tumors,
the effective NK cell labeling with HAPF, magneto-activation, and
MRI contrast effect of NK cells will be beneficial to enhance the
NK cell-therapeutic efficacy in various cancers.
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.
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