Oxygen‐Enriched Metal‐Phenolic X‐Ray Nanoprocessor for Cancer Radio‐Radiodynamic Therapy in Combination with Checkpoint Blockade Immunotherapy

Sang, Wei; Xie, Lisi; Wang, Guohao; Li, Jie; Zhang, Zhan; Li, Bei; Guo, Sen; Deng, Chu‐Xia; Dai, Yunlu

doi:10.1002/advs.202003338

Cited by 114 publications

(107 citation statements)

References 53 publications

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“…[121] To avoid the limitation of non-selectivity, radioresistance, and dose-dependent toxicity to normal tissues, our group synthesized an MPN-based oxygen-enriched X-ray nanoprocessor to improve the therapeutic effect of RT. [122] Hafnium, a high-Z metal ion exhibiting splendid photoelectric effect was used as the linking point of this MPN and employed as a radiosensitizer (Figure 22A). In addition, hafnium also served as a radioluminescence scintillator which can activate the photosensitizer for ROS generation upon X-ray irradiation.…”

Section: Rtmentioning

confidence: 99%

Recent Advances in Metal‐Phenolic Networks for Cancer Theranostics

Zhang

Xie

et al. 2021

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can specially accumulate in tumor sites due to the dysfunctional vasculatures, which is defined as enhanced permeation and retention (EPR) effect. [3] Beyond the physical features, nanomaterials constructing the NPs themselves can also bring in some novel properties such as new therapeutic mechanisms, environment-responsive drug release, stealth and targeting property, and ligand-based immune activation, etc. [4] To endow the NPs with more functions to achieve the enhancement of therapeutic efficacy and precision medicine, much efforts have been made in the field of nanomaterial engineering.Polyphenols, which have been demonstrated to have the effect of anti-tumor, anti-oxidation, anti-radiation, and antithrombosis, exist widely in natural plants such as tea, fruits, vegetables, and cereals. [5] A number of polyphenols have been FDAapproved for food preparation and human health. Polyphenols can be divided into naturally occurring polyphenols and artificial polyphenol derivatives. As the name shows, there remain abundant phenolic moieties that can chelate metal ions in polyphenols. [6] Metal ions play a key role in the field of biomedicine and chemical catalysis. The existence of multivalent metal ions can induce the crosslinking of polyphenols, thereby leading to the self-assembly of metal-phenolic networks (MPNs). The plentiful types of polyphenols and metals endow the MPNs with diverse properties and functions (Figure 1). MPNs, as promising carriers for drug delivery, are fabricated upon the coordination between phenolic ligands and metal ions, without any help of heat, electricity, or other special solvents. Because of the excellent adhesion capability of polyphenols, MPNs can be coated on various substrates or interfaces (serving as templates) regardless of the structures and shapes. The MPNs nanocoating may confer special and desired properties to the original substrates. Meanwhile, in some designs, the templates can be easily removed, thereby leading to the formation of MPN capsules. [7] MPNs can also self-assemble into spherical NPs without a template. [8] By varying the types of polyphenols, metal ions, or the encapsulated cargos, MPNs can be endowed with various functions. [6a,7b,9] For example, gossypol, a type of polyphenol extracted from cotton seeds, can act as both a selfcarrier and a chemical drug. [4b] Metal ions existed in MPNs not only help to crosslink polyphenols, but also achieve other functions such as biomedical imaging, changing of signaling pathway, and treatment. [6a,10] For example, gadolinium ions (Gd 3+ ) were assembled into MPNs to realize the function of T 1 -weighted Nanomedicine integrates different functional materials to realize the customization of carriers, aiming at increasing the cancer therapeutic efficacy and reducing the off-target toxicity. However, efforts on developing new drug carriers that combine precise diagnosis and accurate treatment have met challenges of uneasy synthesis, poor stability, difficult metabolism, and high cytotoxicity. Metal-phenolic networks...

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Section: Rtmentioning

confidence: 99%

Recent Advances in Metal‐Phenolic Networks for Cancer Theranostics

Zhang

Xie

et al. 2021

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“…[ 167 ] Moreover, utilizing the interfacial coordination interactions between the Ag + ion at the surface of Ag NPs and O/N atom of a fluorescent cyano‐carboxylic derivative (noted as CECZA), a two‐photon PTT agent was fabricated through self‐assembly of Ag NPs and CECZA, and the assemblies demonstrated good PTT effect on HeLa cells. [ 168 ] Apart from the works mentioned above, there are others studies on the use of the coordination effect derived from V 3+/4+ , [ 24 , 169 ] Zr 4+ , [ 170 ] Ag + , [ 171 ] Hf 4+ , [ 91 , 92 , 93 , 94 ] Sn 4+ , [ 172 ] Re + , [ 173 ] Ir 3+ , [ 174 ] and Bi 3+[ 175 ] to fabricate various nanoplatforms for cancer theranostic investigation.…”

Section: Metal‐coordinated Supramolecular Self‐assemblies For Cancer Theranosticsmentioning

confidence: 99%

Metal‐Coordinated Supramolecular Self‐Assemblies for Cancer Theranostics

Wang

Jin

et al. 2021

Advanced Science

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Metal‐coordinated supramolecular nanoassemblies have recently attracted extensive attention as materials for cancer theranostics. Owing to their unique physicochemical properties, metal‐coordinated supramolecular self‐assemblies can bridge the boundary between traditional inorganic and organic materials. By tailoring the structural components of the metal ions and binding ligands, numerous multifunctional theranostic nanomedicines can be constructed. Metal‐coordinated supramolecular nanoassemblies can modulate the tumor microenvironment (TME), thus facilitating the development of TME‐responsive nanomedicines. More importantly, TME‐responsive organic–inorganic hybrid nanomaterials can be constructed in vivo by exploiting the metal‐coordinated self‐assembly of a variety of functional ligands, which is a promising strategy for enhancing the tumor accumulation of theranostic molecules. In this review, recent advancements in the design and fabrication of metal‐coordinated supramolecular nanomedicines for cancer theranostics are highlighted. These supramolecular compounds are classified according to the order in which the coordinated metal ions appear in the periodic table. Furthermore, the prospects and challenges of metal‐coordinated supramolecular self‐assemblies for both technical advances and clinical translation are discussed. In particular, the superiority of TME‐responsive nanomedicines for in vivo coordinated self‐assembly is elaborated, with an emphasis on strategies that enhance the accumulation of functional components in tumors for an ideal theranostic outcome.

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“…Besides macrophage activation and NK cell recruitment, tumor infiltration by CD4+ T cells also plays a pivotal role [105]. The first attempts to integrate tools for modulating hypoxia of tumor microenvironment by the enhanced oxygen-carrying capacity of a specifically assembled hemoglobin with high radiation dose per fraction (8 Gy) and immunotherapy (anti-PD-1 antibody) have already been effectively made in experimental animal models [106]. Then, to optimize radiotherapy effects, the definition of suited time points to exploit tumor oxygen dynamics for adaptive dose-painting in fractionated schedules and to include immunotherapies for reducing the cumulative dose of radiation is required.…”

Section: A Look To the Future And Open Questionsmentioning

confidence: 99%

Lattice or Oxygen-Guided Radiotherapy: What If They Converge? Possible Future Directions in the Era of Immunotherapy

Ferini¹,

Valenti²,

Tripoli³

et al. 2021

Cancers

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Palliative radiotherapy has a great role in the treatment of large tumor masses. However, treating a bulky disease could be difficult, especially in critical anatomical areas. In daily clinical practice, short course hypofractionated radiotherapy is delivered in order to control the symptomatic disease. Radiation fields generally encompass the entire tumor mass, which is homogeneously irradiated. Recent technological advances enable delivering a higher radiation dose in small areas within a large mass. This goal, previously achieved thanks to the GRID approach, is now achievable using the newest concept of LATTICE radiotherapy (LT-RT). This kind of treatment allows exploiting various radiation effects, such as bystander and abscopal effects. These events may be enhanced by the concomitant use of immunotherapy, with the latter being ever more successfully delivered in cancer patients. Moreover, a critical issue in the treatment of large masses is the inhomogeneous intratumoral distribution of well-oxygenated and hypo-oxygenated areas. It is well known that hypoxic areas are more resistant to the killing effect of radiation, hence the need to target them with higher aggressive doses. This concept introduces the “oxygen-guided radiation therapy” (OGRT), which means looking for suitable hypoxic markers to implement in PET/CT and Magnetic Resonance Imaging. Future treatment strategies are likely to involve combinations of LT-RT, OGRT, and immunotherapy. In this paper, we review the radiobiological rationale behind a potential benefit of LT-RT and OGRT, and we summarize the results reported in the few clinical trials published so far regarding these issues. Lastly, we suggest what future perspectives may emerge by combining immunotherapy with LT-RT/OGRT.

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Oxygen‐Enriched Metal‐Phenolic X‐Ray Nanoprocessor for Cancer Radio‐Radiodynamic Therapy in Combination with Checkpoint Blockade Immunotherapy

Cited by 114 publications

References 53 publications

Recent Advances in Metal‐Phenolic Networks for Cancer Theranostics

Recent Advances in Metal‐Phenolic Networks for Cancer Theranostics

Metal‐Coordinated Supramolecular Self‐Assemblies for Cancer Theranostics

Lattice or Oxygen-Guided Radiotherapy: What If They Converge? Possible Future Directions in the Era of Immunotherapy

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