Abstract:Herein we report the design of a
bacteriochlorin-based nanoscale
metal–organic framework, Zr-TBB, for highly effective photodynamic
therapy via both type I and type II mechanisms. The framework of Zr-TBB
stabilizes 5,10,15,20-tetra(p-benzoato)bacteriochlorin
(TBB) ligands toward oxygen and light via geometrical constraint.
Upon 740 nm light irradiation, Zr-TBB efficiently generates various
reactive oxygen species, including singlet oxygen, superoxide anion,
hydrogen peroxide, and hydroxyl radicals, to afford… Show more
“…(4) Relatively labile coordination bond connections make nMOFs intrinsically biodegradable in physiological environments for biocompatibility. As a result, nMOFs have been successfully applied to the delivery of chemotherapeutic agents, [200][201][202] imaging contrast agents, 172, 203 photosensitizers, [204][205][206][207][208][209][210][211][212][213] proteins [214][215] and gene therapy drugs. [216][217][218] In this dissertation, I report the progress on the design of nMOFs as nanosensitizers to enhance RT, 219 mediate radiotherapy-radiodynamic therapy (RT-RDT), [220][221] and enable PDT and CDT 222 with the advantages of high payload, crystalline order, and porous structures for ROS generation.…”
Section: Nanoscale Metal-organic Framework For Cancer Immunotherapymentioning
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...
“…(4) Relatively labile coordination bond connections make nMOFs intrinsically biodegradable in physiological environments for biocompatibility. As a result, nMOFs have been successfully applied to the delivery of chemotherapeutic agents, [200][201][202] imaging contrast agents, 172, 203 photosensitizers, [204][205][206][207][208][209][210][211][212][213] proteins [214][215] and gene therapy drugs. [216][217][218] In this dissertation, I report the progress on the design of nMOFs as nanosensitizers to enhance RT, 219 mediate radiotherapy-radiodynamic therapy (RT-RDT), [220][221] and enable PDT and CDT 222 with the advantages of high payload, crystalline order, and porous structures for ROS generation.…”
Section: Nanoscale Metal-organic Framework For Cancer Immunotherapymentioning
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...
“…PDT by DBP-UiO exhibited outstanding antitumor performance toward the drug-resistant tumors under 640 nm light irradiation with a dose of 90 J cm −2 . The therapeutic efficacy of DBP-UiO could be attributed to the enhanced 1 O 2 generation efficiency induced by the heavy atom effect of Hf and ROS diffusion inside the MOF structures [ 98 ]. Fig.…”
In recent years, reactive species-based cancer therapies have attracted tremendous attention due to their simplicity, controllability, and effectiveness. Herein, we overviewed the state-of-art advance for photo-controlled generation of highly reactive radical species with nanomaterials for cancer therapy. First, we summarized the most widely explored reactive species, such as singlet oxygen, superoxide radical anion (O
2
●-
), nitric oxide (
●
NO), carbon monoxide, alkyl radicals, and their corresponding secondary reactive species generated by interaction with other biological molecules. Then, we discussed the generating mechanisms of these highly reactive species stimulated by light irradiation, followed by their anticancer effect, and the synergetic principles with other therapeutic modalities. This review might unveil the advantages of reactive species-based therapeutic methodology and encourage the pre-clinical exploration of reactive species-mediated cancer treatments.
“…Additionally, some PSs are unstable towards oxygen and light. The photobleaching of PSs significantly reduces the efficacy of PDT, hindering the clinical application of PDT [22][23][24][25] . Therefore, to achieve the clinical treatment of deep tumors, it is urgent to develop highly stable, less oxygen-dependent PSs with strong NIR absorption for enhancing PDT efficacy.…”
Photodynamic therapy (PDT) greatly suffers from the weak NIR-absorption, oxygen dependence and poor stability of photosensitizers (PSs). Herein, inspired by natural bacteriochlorin, we develop a bacteriochlorin analogue, tetrafluorophenyl bacteriochlorin (FBC),...
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