Conspectus
Cancer immunotherapy, particularly checkpoint
blockade immunotherapy
(CBI), has revolutionized the treatment of some cancers by reactivating
the antitumor immunity of hosts with durable response and manageable
toxicity. However, many cancer patients with low tumor antigen exposure
and immunosuppressive tumor microenvironments do not respond to CBI.
A variety of methods have been investigated to reverse immunosuppressive
tumor microenvironments and turn “cold” tumors “hot”
with the goal of extending the therapeutic benefits of CBI to a broader
population of cancer patients. Immunostimulatory adjuvant treatments,
such as cancer vaccines, photodynamic therapy (PDT), radiotherapy
(RT), radiotherapy–radiodynamic therapy (RT-RDT), and chemodynamic
therapy (CDT), promote antigen presentation and T cell priming and,
when used in combination with CBI, reactivate and sustain systemic
antitumor immunity. Cancer vaccines directly provide tumor antigens,
while immunoadjuvant therapies such as PDT, RT, RT-RDT, and CDT kill
cancer cells in an immunogenic fashion to release tumor antigens in situ. Direct administration of tumor antigens or indirect
intratumoral immunoadjuvant therapies as in situ cancer
vaccines initiate the immuno-oncology cycle for antitumor immune response.
With the rapid growth of cancer nanotechnology in the past two
decades, a large number of nanoparticle platforms have been studied,
and some nanomedicines have been translated into clinical trials.
Nanomedicine provides a promising strategy to enhance the efficacy
of immunoadjuvant therapies to potentiate cancer immunotherapy. Among
these nanoparticle platforms, nanoscale metal–organic frameworks
(nMOFs) have emerged as a unique class of porous hybrid nanomaterials
with metal cluster secondary building units and organic linkers. With
molecular modularity, structural tunability, intrinsic porosity, tunable
stability, and biocompatibility, nMOFs are ideally suited for biomedical
applications, particularly cancer treatments.
In this Account,
we present recent breakthroughs in the design
of nMOFs as nanocarriers for cancer vaccine delivery and as nanosensitizers
for PDT, CDT, RT, and RT-RDT. The versatility of nMOFs allows them
to be fine-tuned to effectively load tumor antigens and immunoadjuvants
as cancer vaccines and significantly enhance the local antitumor efficacy
of PDT, RT, RT-RDT, and CDT via generation of reactive
oxygen species (ROS) for in situ cancer vaccination.
These nMOF-based treatments are further combined with cancer immunotherapies
to elicit systemic antitumor immunity. We discuss novel strategies
to enhance light tissue penetration and overcome tumor hypoxia in
PDT, to increase energy deposition and ROS diffusion in RT, to combine
the advantages of PDT and RT to enable RT-RDT, and to trigger CDT
by hijacking aberrant metabolic processes in tumors. Loading nMOFs
with small-molecule drugs such as an indoleamine 2,3-dioxygenase inhibitor,
the toll-like receptor agonist imiquimod, and biomacromolecules such
as CpG oligodeoxynucleot...
