In Vivo Regenerable Cerium Oxide Nanozyme-Loaded pH/H₂O₂-Responsive Nanovesicle for Tumor-Targeted Photothermal and Photodynamic Therapies

Abstract

Photodynamic therapy (PDT) and photothermal therapies (PTTs) are both promising strategies for effective tumor therapy. However, the absence of O 2 at tumor sites hinders the sustained response of photosensitizers. Here, we develop a recycled cerium oxide (CeO 2 ) catalase nanozyme-loaded hyaluronic acid nanovesicle to address the hypoxic tumor microenvironments and targeted delivery of the photosensitizers [indocyanine green (ICG)] to tumors. A polysaccharide complex effectively modifies the surface of a polyethylenimine phenylboronic acid nanostructure to achieve the CeO 2 nanozyme-loading nanovesicles that exhibit both tumor-targeted enhancement and an improved hypoxic microenvironment. Also, the hydrogen peroxide responsiveness and acid-sensitive cleavage of phenylboronic acid specifically disintegrate the ICG/nanozyme coloaded nanovesicles in the tumor microenvironment. The in vitro synergistic tests and tumor suppression rate tests indicated that the cerium oxide nanozyme significantly improves the outcomes of PDT via ceriumelement valence state recycling and hypoxia improvement, thus enhancing the tumor suppression efficiency. This pH/H 2 O 2responsive nanozyme/ICG codelivery system provides a good carrier model for improving the tumor microenvironment and increasing the efficiency of tumor-targeted PTT and PDT therapies.

An intelligent responsive macrophage cell membrane-camouflaged mesoporous silicon nanorod drug delivery system for precise targeted therapy of tumors

“…Due to the lack of high selectivity and specificity, the aggregation effect of nanocarriers without active targeting on tumor tissues is low [ 11 – 14 ]. Therefore, nanocarriers with specific modifications that enable binding to tumor cell surface receptors or antigens are desirable for site-specific targeting [ 15 – 18 ]. The hydrophobic and electrical properties of these targeted groups on nanocarriers may reduce their time in circulation.…”

Reactive Oxygen Species-Based Nanomaterials for Cancer Therapy

“…Given their antioxidation properties, cerium oxide NPs may be used to deliver oxygen to tumor regions. Indeed, it was shown that cerium oxide NPs generate O 2 inside tumors by consuming endogenous H 2 O 2 (Yao et al, 2018;Liu et al, 2020;Zeng et al, 2020). For example, Yao et al (2018) reported that a synergetic mesoporous cerium oxide upconversion nanoparticle (Ce-UCNP; Figure 3 to trigger cellular apoptosis.…”

Smart Polymeric Delivery System for Antitumor and Antimicrobial Photodynamic Therapy

“…For instance, the concentration of hydrogen peroxide in tumor cells is reported to be approximately 10 μM, which is higher than normal cells. Boronic acid esters are typical hydrogen peroxide-responsive moieties ( Saravanakumar et al, 2017 ; Zeng et al, 2020 ). In addition, GSH is abundant in a tumor intracellular environment (2–10 mM) ( Li and Yan, 2018 ).…”

“…Based on the different microenvironments of tumor and normal tissues, a variety of activatable polymeric delivery systems are emerging ( Park et al, 2016 ; Sun et al, 2017 ; Wei et al, 2018 ; Li et al, 2019c ; Yan et al, 2020 ; Zeng et al, 2020 ; Yang et al, 2021 ). Despite the different structures and constituents of thousands of reports, they mainly achieve the activation via the following three strategies: (1) self-quenching and dequenching of photosensitizers due to aggregation and disintegration; (2) utilize another quencher to quench the triplet state of photosensitizer and dequenching upon cleavage of sensitive bonds; and (3) the change of size and surface charge to induce an enhanced internalization by tumor cells.…”