Cancer immunotherapies that train or stimulate the inherent immunological systems to recognize, attack, and eradicate tumor cells with minimal damage to healthy cells have demonstrated promising ...clinical responses in recent years. However, most of these immunotherapeutic strategies only benefit a small subset of patients and cause systemic autoimmune side effects in some patients. Immunogenic cell death (ICD)‐inducing modalities not only directly kill cancer cells but also induce antitumor immune responses against a broad spectrum of solid tumors. Such strategies for generating vaccine‐like functions could be used to stimulate a “cold” tumor microenvironment to become an immunogenic, “hot” tumor microenvironment, working in synergy with immunotherapies to increase patient response rates and lead to successful treatment outcomes. This Minireview will focus on nanoparticle‐based treatment modalities that can induce and enhance ICD to potentiate cancer immunotherapy.
Nanoparticle‐mediated immunogenic cell death directly kills cancer cells and induces antitumor immune responses. Such in situ vaccination strategies can be used to activate the tumor microenvironment to synergize with cancer immunotherapies to improve patient response rates and treatment outcomes.
We calculate the metric of a self-gravitating and collapsing infinitely thin spherical shell in the weak-field and slow-motion limits, and we demonstrate that Birkhoff’s theorem is not consistent ...with the theory of the post-Newtonian approximation. More importantly, it is illustrated that performing a coordinate transformation in solving Einstein field equations may change the matter energy-momentum tensor, making the resultant solution not correspond to the original problem.
Photodynamic therapy (PDT) is an effective anticancer procedure that relies on tumor localization of a photosensitizer followed by light activation to generate cytotoxic reactive oxygen species ...(e.g., 1O2). Here we report the rational design of a Hf–porphyrin nanoscale metal–organic framework, DBP–UiO, as an exceptionally effective photosensitizer for PDT of resistant head and neck cancer. DBP–UiO efficiently generates 1O2 owing to site isolation of porphyrin ligands, enhanced intersystem crossing by heavy Hf centers, and facile 1O2 diffusion through porous DBP–UiO nanoplates. Consequently, DBP–UiO displayed greatly enhanced PDT efficacy both in vitro and in vivo, leading to complete tumor eradication in half of the mice receiving a single DBP–UiO dose and a single light exposure. NMOFs thus represent a new class of highly potent PDT agents and hold great promise in treating resistant cancers in the clinic.
Ovarian cancer is the leading cause of death among women with gynecological malignancies. Acquired resistance to chemotherapy is a major limitation for ovarian cancer treatment. We report here the ...first use of nanoscale metal–organic frameworks (NMOFs) for the co-delivery of cisplatin and pooled small interfering RNAs (siRNAs) to enhance therapeutic efficacy by silencing multiple drug resistance (MDR) genes and resensitizing resistant ovarian cancer cells to cisplatin treatment. UiO NMOFs with hexagonal-plate morphologies were loaded with a cisplatin prodrug and MDR gene-silencing siRNAs (Bcl-2, P-glycoprotein P-gp, and survivin) via encapsulation and surface coordination, respectively. NMOFs protect siRNAs from nuclease degradation, enhance siRNA cellular uptake, and promote siRNA escape from endosomes to silence MDR genes in cisplatin-resistant ovarian cancer cells. Co-delivery of cisplatin and siRNAs with NMOFs led to an order of magnitude enhancement in chemotherapeutic efficacy in vitro, as indicated by cell viability assay, DNA laddering, and Annexin V staining. This work shows that NMOFs hold great promise in the co-delivery of multiple therapeutics for effective treatment of drug-resistant cancers.
Metal-organic frameworks (MOFs), also known as coordination polymers, represent an interesting class of crystalline molecular materials that are synthesized by combining metal-connecting points and ...bridging ligands. The modular nature of and mild conditions for MOF synthesis have permitted the rational structural design of numerous MOFs and the incorporation of various functionalities via constituent building blocks. The resulting designer MOFs have shown promise for applications in a number of areas, including gas storage/separation, nonlinear optics/ferroelectricity, catalysis, energy conversion/storage, chemical sensing, biomedical imaging, and drug delivery. The structure-property relationships of MOFs can also be readily established by taking advantage of the knowledge of their detailed atomic structures, which enables fine-tuning of their functionalities for desired applications. Through the combination of molecular synthesis and crystal engineering, MOFs thus present an unprecedented opportunity for the rational and precise design of functional materials.
We report here the rational design of the first chlorin-based nanoscale metal-organic framework (NMOF), DBC-UiO, with much improved photophysical properties over the previously reported ...porphyrin-based NMOF, DBP-UiO. Reduction of the DBP ligands in DBP-UiO to the DBC ligands in DBC-UiO led to a 13 nm red shift and an 11-fold increase in the extinction coefficient of the lowest-energy Q band. While inheriting the crystallinity, stability, porosity, and nanoplate morphology of DBP-UiO, DBC-UiO sensitizes more efficient (1)O2 generation and exhibits significantly enhanced photodynamic therapy (PDT) efficacy on two colon cancer mouse models as a result of its improved photophysical properties. Both apoptosis and immunogenic cell death contributed to killing of cancer cells in DBC-UiO-induced PDT.
Metal-organic frameworks (MOFs) are a class of hybrid materials self-assembled from organic bridging ligands and metal ion/cluster connecting points. The combination of a variety of organic linkers, ...metal ions/clusters, and structural motifs can lead to an infinite array of new materials with interesting properties for many applications. In this Forum Article, we discuss the design and applications of MOFs in chemical sensing and biological imaging. The first half of this article focuses on the development of MOFs as chemical sensors by highlighting how unique attributes of MOFs can be utilized to enhance sensitivity and selectivity. We also discuss some of the issues that need to be addressed in order to develop practically useful MOF sensors. The second half of this article focuses on the design and applications of nanoscale MOFs (NMOFs) as imaging contrast agents. NMOFs possess several interesting attributes, such as high cargo loading capacity, ease of postmodification, tunable size and shape, and intrinsic biodegradability, to make them excellent candidates as imaging contrast agents. We discuss the use of representative NMOFs in magnetic resonance imaging (MRI), X-ray computed tomography (CT), and optical imaging. Although still in their infancy, we believe that the compositional tunability and mild synthetic conditions of NMOF imaging agents should greatly facilitate their further development for clinical translation.
We explore the inflationary dynamics and reheating predictions of the fourth-order generalized polynomial inflation model featuring adjustable saddle-point position and flatness near the saddle point ...for both small and large field cases, based on the latest Planck 2018 Cosmic Microwave Background (CMB) and BICEP/Keck data. We observe that the small field case, with saddle points proximate to the origin, exhibits a significantly lower tensor-to-scalar ratio compared to the large field case. Additionally, the spectral index of the curvature perturbation increases as the flatness near the potential saddle point decreases. Through an analysis of the interplay between inflation and reheating parameters derived from the expansion history of the pivot CMB scale, we establish a permissible range for the reheating parameters. We find that both the small and large cases of polynomial inflation can be consistent with the latest observations due to potential flatness reduction, except for the case where the saddle point deviates significantly from the origin, and the reheating process accentuates the disparities in parameter space between small and large field inflationary scenarios.
Immunotherapy has become a promising cancer therapy, but only works for a subset of cancer patients. Immunogenic photodynamic therapy (PDT) can prime cancer immunotherapy to increase the response ...rates, but its efficacy is severely limited by tumor hypoxia. Here we report a nanoscale metal-organic framework, Fe-TBP, as a novel nanophotosensitizer to overcome tumor hypoxia and sensitize effective PDT, priming non-inflamed tumors for cancer immunotherapy. Fe-TBP was built from iron-oxo clusters and porphyrin ligands and sensitized PDT under both normoxic and hypoxic conditions. Fe-TBP mediated PDT significantly improved the efficacy of anti-programmed death-ligand 1 (α-PD-L1) treatment and elicited abscopal effects in a mouse model of colorectal cancer, resulting in >90% regression of tumors. Mechanistic studies revealed that Fe-TBP mediated PDT induced significant tumor infiltration of cytotoxic T cells.
This paper highlights the most significant recent advances in the synthesis, characterization, and applications of single-crystalline homochiral porous metal-organic frameworks (MOFs). The ...motivations for the synthesis of homochiral porous solids and the strategies on how they can be designed are provided. The latest examples of chiral separation and Lewis acid heterogeneous asymmetric catalysis using homochiral porous MOFs are presented.
A schematic representation of the active (BINOLate)Ti(O
i
Pr)
2 catalytic sites inside the open channels of a homochiral porous MOF.
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