Hybrid Protein Nano‐Reactors Enable Simultaneous Increments of Tumor Oxygenation and Iodine‐131 Delivery for Enhanced Radionuclide Therapy

Abstract

It is hard for current radionuclide therapy to render solid tumors desirable therapeutic efficacy owing to insufficient tumor‐targeted delivery of radionuclides and severe tumor hypoxia. In this study, a biocompatible hybrid protein nanoreactor composed of human serum albumin (HSA) and catalase (CAT) molecules is constructed via glutaraldehyde‐mediated crosslinking. The obtained HSA‐CAT nanoreactors (NRs) show retained and well‐protected enzyme stability in catalyzing the decomposition of H2O2 and enable efficient labeling of therapeutic radionuclide iodine‐131 (131I). Then, it is uncovered that such HSA‐CAT NRs after being intravenously injected into tumor‐bearing mice exhibit efficient passive tumor accumulation as vividly visualized under the fluorescence imaging system and gamma camera. As the result, such HSA‐CAT NRs upon tumor accumulation would significantly attenuate tumor hypoxia by decomposing endogenous H2O2 produced by cancer cells to molecular oxygen, and thereby remarkably improve the therapeutic efficacy of radionuclide 131I. This study highlights the concise preparation of biocompatible protein nanoreactors with efficient tumor homing and hypoxia attenuation capacities, thus enabling greatly improved tumor radionuclide therapy with promising potential for future clinical translation.

Reversing cold tumors to hot: An immunoadjuvant-functionalized metal-organic framework for multimodal imaging-guided synergistic photo-immunotherapy

“…Therefore, it is highly desirable to improve the immune response rate and selectively destroy primary solid tumors and metastatic lesions. In recent years, immunotherapy combined with nanotechnology, defined as nanoimmunotherapy, has shown promising performance for cancer therapy [ [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] ]. Among these therapeutics, metal-organic frameworks (MOFs), as a crystal material, has been widely studied in biomedical field [ [31] , [32] , [33] , [34] , [35] , [36] , [37] ].…”

Construction of Enzyme Nanoreactors to Enable Tumor Microenvironment Modulation and Enhanced Cancer Treatment

“…[ 62 ] Moreover, ascribing to the abundant tyrosine residues of catalase and other proteins could be utilized for efficient labeling of iodine radioisotopes (e.g., 125 I and 131 I), we recently prepared a type of hybrid protein nanoreactors composed of HSA and catalase molecules via the glutaraldehyde mediated crosslinking. [ 63 ] The obtained nanoreactors upon intravenous injection would passively home to tumor site, and enable efficient tumor accumulation of radioisotope of 131 I and tumor oxygenation, thereby realizing greatly improved internal radiation therapy.…”

Exoskeleton for Biofunctionality Protection of Enzymes and Proteins for Intracellular Delivery

“…[ 45 ] According to recent trends, the decomposition of H 2 O 2 and generation of O 2 have been explored for remedy of hypoxia‐associated room temperature resistance by challenging the hypoxic tumor microenvironment. [ 46 ] Nevertheless, TaO x ‐entrapped CAT was explored for radiation therapy of tumor by CAT delivery for hypoxia relieve of tumor microenvironment. [ 44 ] The efficacy of ZIF‐protected CAT can be a suitable candidate for advanced study under chemo‐, radio‐, and photodynamic therapy via suitable modification of Cat@ZIF‐8.…”

“…In a hybrid protein nanoreactor, the biofunctionality protection mechanism of the reactor involves the glutaraldehyde based crosslinking of HSA and CAT. [ 46 ] This crosslinking provides the nanoreactor with an excellent physiological stability. A CAT–poly(acrylic acid) (PAA) bioconjugate acts toward retaining its native‐like structure while delivering CAT activity with significant improvement due to covalent conjugation with PAA.…”

“…A biocompatible protein nanoreactor is made of human serum albumin (HSA) and CAT with a glutaraldehyde‐mediated crosslinking strategy. [ 46 ] This protein nanoreactor is intravenously injected into the tumor‐bearing mice model which was then visualized under the fluorescence imaging system, which showed significant attenuate tumor hypoxia by decomposing endogenous H 2 O 2 in cancer cells to O 2 molecule. Therefore, the role of the nanoreactor for protein delivery in tumor radionuclide therapy to induce thermal and pH stability, however, needs further analysis.…”