Zinc-substituted hemoglobin with specific drug binding sites and fatty acid resistance ability for enhanced photodynamic therapy

Xu, Yiting; Xu, Jiamei; Hu, Xiaoxiao; Dong, Qian; Liu, Zhangkun; Chen, Zhuo; Tan, Weihong

doi:10.1007/s12274-019-2452-2

Cited by 17 publications

(17 citation statements)

References 59 publications

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“…In this work 89 Zr was used as a radiolabel to monitor the in vivo biodistribution of human Hb injected in mouse models by PET/CT. Hb has recently moved to the center stage of biomedicine as a potential carrier of drugs [3,4,26,27]; it can be readily obtained either directly from patients or as a highly purified biopharmaceutical protein, it is biocompatible, non-antigenic, it undergoes naturally controlled degradation processes, it is amenable to genetic or chemical modifications and it shows unique pharmacokinetic properties [3,4,28,29]. We employed chemically modified Hb with maleimide-deferoxamine as a chelating agent for 89 Zr.…”

Section: Discussionmentioning

confidence: 99%

Biodistribution PET/CT Study of Hemoglobin-DFO-89Zr Complex in Healthy and Lung Tumor-Bearing Mice

Kiraga

Cerutti

Braniewska

et al. 2020

IJMS

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Proteins, as a major component of organisms, are considered the preferred biomaterials for drug delivery vehicles. Hemoglobin (Hb) has been recently rediscovered as a potential drug carrier, but its use for biomedical applications still lacks extensive investigation. To further explore the possibility of utilizing Hb as a potential tumor targeting drug carrier, we examined and compared the biodistribution of Hb in healthy and lung tumor-bearing mice, using for the first time 89Zr labelled Hb in a positron emission tomography (PET) measurement. Hb displays a very high conjugation yield in its fast and selective reaction with the maleimide-deferoxamine (DFO) bifunctional chelator. The high-resolution X-ray structure of the Hb-DFO complex demonstrated that cysteine β93 is the sole attachment moiety to the αβ-protomer of Hb. The Hb-DFO complex shows quantitative uptake of 89Zr in solution as determined by radiochromatography. Injection of 0.03 mg of Hb-DFO-89Zr complex in healthy mice indicates very high radioactivity in liver, followed by spleen and lungs, whereas a threefold increased dosage results in intensification of PET signal in kidneys and decreased signal in liver and spleen. No difference in biodistribution pattern is observed between naïve and tumor-bearing mice. Interestingly, the liver Hb uptake did not decrease upon clodronate-mediated macrophage depletion, indicating that other immune cells contribute to Hb clearance. This finding is of particular interest for rapidly developing clinical immunology and projects aiming to target, label or specifically deliver agents to immune cells.

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Section: Discussionmentioning

confidence: 99%

Biodistribution PET/CT Study of Hemoglobin-DFO-89Zr Complex in Healthy and Lung Tumor-Bearing Mice

Kiraga

Cerutti

Braniewska

et al. 2020

IJMS

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“…However, porphyrins in their original forms generally have poor photodynamic activity, hence PDT systems mostly uses porphyrin derivatives, which could have higher efficiency, as the photosensitizer [39] . For example, chlorophyll and heme are widely used in PDT, since both are endogenous products of natural organisms with superior biocompatibility and high efficiency [40] . Below, we will review various strategies to further improve clinical performance of porphyrin-based PDTs such as using modified porphyrin derivatives or porphyrin precursors, designing specific delivery vehicle, and applying combined therapies.…”

Section: Porphyrin and Porphyrin Derivativesmentioning

confidence: 99%

Advances in photosensitizer-related design for photodynamic therapy

Zhou

Zhang

et al. 2021

Asian Journal of Pharmaceutical Sciences

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Photodynamic therapy (PDT) is highly effective in treating tumors located near body surface, offering strong tumor suppression and low damage to normal tissue nearby. PDT is also effective for treating a number of other conditions. PDT not only provide a precise and selective method for the treatment of various diseases by itself, it can also be used in combination with other traditional therapies. Because PDT uses light as the unique targeting mechanism, it has simpler and more direct targeting capability than traditional therapies. The core material of a PDT system is the photosensitizer which converts light energy to therapeutic factors/substances. Different photosensitizers have their distinct characteristics, leading to different advantages and disadvantages. These could be enhanced or compensated by using proper PDT system. Therefore, the selected type of photosensitizer would heavily influence the overall design of a PDT system. In this article, we evaluated major types of inorganic and organic PDT photosensitizers, and discussed future research directions in the field.

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“…159 In view of this, Tan's group developed a folate acid (FA) modified, zinc-substituted hemoglobin as a photosensitizer (ZnPHb-FA) for PDT. 160 To develop this nanoplatform, hemin, or Fe protoporphyrin (FePPIX) in human hemoglobin was replaced with ZnPPIX, then the modified hemoglobin (ZnPHb) was decorated with FA, a tumor-targeting ligand (Figure 8e). Due to the inhibitory effect of ZnPHb against HO-1 and the photosensitizing capability of porphyrins, this protein-based nanoagent enabled enhanced photodynamic effect by lowering antioxidant defense (Figure 8f).…”

Section: Barriers To Pdtmentioning

confidence: 99%

Section: Multifunctional Nanoassemblies For Enhanced Pdtmentioning

confidence: 99%

“…Hemin oxygenase-1 (HO-1) is an endogenous protein that reduces hemin to biliverdin, which is in turn reduced by biliverdin reductase to produce bilirubin, an antioxidant that is much more potent than glutathione . In view of this, Tan’s group developed a folate acid (FA) modified, zinc-substituted hemoglobin as a photosensitizer (ZnPHb-FA) for PDT . To develop this nanoplatform, hemin, or Fe protoporphyrin (FePPIX) in human hemoglobin was replaced with ZnPPIX, then the modified hemoglobin (ZnPHb) was decorated with FA, a tumor-targeting ligand (Figure e).…”

Section: Multifunctional Nanoassemblies For Enhanced Pdtmentioning

confidence: 99%

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Remodeling Tumor Microenvironment by Multifunctional Nanoassemblies for Enhanced Photodynamic Cancer Therapy

Liang

Zhang

Yang

et al. 2020

ACS Materials Lett.

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Photodynamic therapy (PDT) is a clinically implemented modality to tackle intractable diseases, including cancer. Nevertheless, its efficacy is largely compromised by some resistance factors from the complex tumor microenvironment (TME) with various biological barriers. Inspiringly, recent development in nanotechnology has revitalized photodynamic cancer therapy based on rationally designed nanoplatforms that can boost PDT through remodeling TME. Here, we first provide an overview of the microenvironment in solid tumors and the PDT-resistance factors therein. On this basis, we discuss strategies to design multifunctional nanoassemblies and underlying working mechanisms to enhance photodynamic cancer therapy by modulating tumor vasculatures, extracellular matrix, hypoxia, antioxidant defense, and immune suppression. Finally, we highlight the potential and challenges in this burgeoning research field.

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Zinc-substituted hemoglobin with specific drug binding sites and fatty acid resistance ability for enhanced photodynamic therapy

Cited by 17 publications

References 59 publications

Biodistribution PET/CT Study of Hemoglobin-DFO-89Zr Complex in Healthy and Lung Tumor-Bearing Mice

Biodistribution PET/CT Study of Hemoglobin-DFO-89Zr Complex in Healthy and Lung Tumor-Bearing Mice

Advances in photosensitizer-related design for photodynamic therapy

Remodeling Tumor Microenvironment by Multifunctional Nanoassemblies for Enhanced Photodynamic Cancer Therapy

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