Albumin‐Templated Manganese Dioxide Nanoparticles for Enhanced Radioisotope Therapy

Abstract

Although nanoparticle-based drug delivery systems have been widely explored for tumor-targeted delivery of radioisotope therapy (RIT), the hypoxia zones of tumors on one hand can hardly be reached by nanoparticles with relatively large sizes due to their limited intratumoral diffusion ability, on the other hand often exhibit hypoxia-associated resistance to radiation-induced cell damage. To improve RIT treatment of solid tumors, herein, radionuclide I labeled human serum albumin (HSA)-bound manganese dioxide nanoparticles ( I-HSA-MnO ) are developed as a novel RIT nanomedicine platform that is responsive to the tumor microenvironment (TME). Such I-HSA-MnO nanoparticles with suitable sizes during blood circulation show rather efficient tumor passive uptake owing to the enhanced permeability and retention effect, as well as little retention in other normal organs to minimize radiotoxicity. The acidic TME can trigger gradual degradation of MnO and thus decomposition of I-HSA-MnO nanoparticles into individual I-HSA with sub-10 nm sizes and greatly improves intratumoral diffusion. Furthermore, oxygen produced by MnO -triggered decomposition of tumor endogenous H O would be helpful to relieve hypoxia-associated RIT resistant for those tumors. As the results, the I-HSA-MnO nanoparticles appear to be a highly effective RIT agent showing great efficacy in tumor treatment upon systemic administration.

Manganese Dioxide Nanozymes as Responsive Cytoprotective Shells for Individual Living Cell Encapsulation

“…[26][27][28] Significantly,s everal albumintemplated MnO 2 nanomaterials have served as pH/H 2 O 2 stimuli-responsive nanoplatforms for tumor imaging and elimination. [29,30] Therefore,w ee nvision that the efficient coating for individual living cells with MnO 2 -based nanozymes can fulfill the criteria such as strong resistance to harsh environments,a nd potential biodegradation upon mild stimulus.…”

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

“…It was found that plain HSA‐CAT NRs exhibited negligible cytotoxicity toward 4T1 cells even at a high incubation concentration of 5 mg mL −1 in term of CAT for 24 h (Figure c), indicating them great biocompatibility. Then, by utilizing the abundant tyrosine residues in both HSA and CAT molecules, these HSA‐CAT NRs were efficient for the labeling of radioactive 131 I by adopting our previously used labeling methods . Then, the cell killing ability of such 131 I‐HSA‐CAT NRs was carefully compared with free 131 I by using the standard MTT assay.…”

“…Regarding radionuclide therapy, it was shown that increased tumor oxygen delivery via photothermally boosted tumor blood perfusion or paclitaxel suppressed expression of hypoxia induced factor 1α (HIF‐1α) could thereby remarkably enhance the treatment outcomes of co‐delivered radioisotopes of Rhenium‐188 ( 188 Rh) and 131 I, respectively. In addition, in a recent work, it was shown that 131 I labeled human serum albumin (HSA)‐bound manganese dioxide nanoparticles ( 131 I‐HSA‐MnO 2 NPs) upon intravenous injection could enable superior tumor accumulation of 131 I via the enhanced permeability and retention (EPR) effect . Moreover, such 131 I‐HSA‐MnO 2 could significantly promote tumor oxygenation via MnO 2 ‐mediated decomposition of endogenous H 2 O 2 , and thereby synergistically enhance the therapeutic efficacy of 131 I.…”

“…In addition, in a recent work, it was shown that 131 I labeled human serum albumin (HSA)‐bound manganese dioxide nanoparticles ( 131 I‐HSA‐MnO 2 NPs) upon intravenous injection could enable superior tumor accumulation of 131 I via the enhanced permeability and retention (EPR) effect . Moreover, such 131 I‐HSA‐MnO 2 could significantly promote tumor oxygenation via MnO 2 ‐mediated decomposition of endogenous H 2 O 2 , and thereby synergistically enhance the therapeutic efficacy of 131 I. However, considering the potential safety risk of manganese ions, development of more biocompatible nanoformulations enabling efficient tumor hypoxia relief and tumor‐targeted radioisotope delivery is still a big challenge for efficient radionuclide therapy.…”

Flexible Cationic Nanoparticles with Photosensitizer Cores for Multifunctional Biomedical Applications

“…The minimally invasive photodynamic therapy (PDT) has been proven to be an alternative treatment to cancer chemotherapy, radiotherapy and surgery over the last decades . Benefiting from the generation of cytotoxic reactive oxygen species (ROS), PDT with photosensitizers possesses capacity to induce tumor cell apoptosis irreversibly . Illumination can be precisely applied onto the pathological tissues without redundant side effects and drug resistance .…”