Engineering of a Nanosized Biocatalyst for Combined Tumor Starvation and Low-Temperature Photothermal Therapy

Abstract

Tumor hypoxia is one of the major challenges for the treatment of tumors, as it may negatively affect the efficacy of various anticancer modalities. In this study, a tumor-targeted redox-responsive composite biocatalyst is designed and fabricated, which may combine tumor starvation therapy and low-temperature photothermal therapy for the treatment of oxygen-deprived tumors. The nanosystem was prepared by loading porous hollow Prussian Blue nanoparticles (PHPBNs) with glucose oxidase (GOx) and then coating their surface with hyaluronic acid (HA) via redox-cleavable linkage, therefore allowing the nanocarrier to bind specifically with CD44-overexpressing tumor cells while also exerting control over the cargo release profile. The nanocarriers are designed to enhance the efficacy of the hypoxia-suppressed GOx-mediated starvation therapy by catalyzing the decomposition of intratumoral hydroperoxide into oxygen with PHPBNs, and the enhanced glucose depletion by the two complementary biocatalysts may consequently suppress the expression of heat shock proteins (HSPs) after photothermal treatment to reduce their resistance to the PHPBN-mediated low-temperature photothermal therapies.

Enzyme‐Mediated Tumor Starvation and Phototherapy Enhance Mild‐Temperature Photothermal Therapy

“…As we know, the expression of HSPs is intrinsically related to the adenosine triphosphate (ATP) concentration levels. [ 7 ] Thus, inhibiting the intratumoral ATP production via tumor starvation will be another effective way to overcome the HSP‐dependent tumor thermoresistance. For example, glucose oxidase (GOx) can effectively catalyze the oxidation of glucose into gluconic acid [ 8 ] and GOx‐induced glucose consumption has shown the potential for cancer starvation therapy.…”

Programmable Therapeutic Nanodevices with Circular Amplification of H2O2 in the Tumor Microenvironment for Synergistic Cancer Therapy

“…Single AQ4N loaded nanodevices (PNV‐AQ4N) showed only a slight cytotoxicity against Hep3B cells, even under hypoxia where AQ4N could convert into toxic AQ4, this might be ascribed to that PNV‐AQ4N was not able to deconstruct and efficiently release AQ4N only relying on intrinsic intracellular H 2 O 2 but without the help of external massive H 2 O 2 amplified by the enveloped GOD. In contrast, single GOD loaded nanodevices (PNV‐GOD) exhibited an obviously reduced cell viability caused by the oxidative damage of generated H 2 O 2 and the starvation therapy after glucose consumption through GOD catalysis . Compared with these two formulations, PAG with co‐encapsulation of GOD and AQ4N exhibited most significantly enhanced anticancer effect, with a very low cell viability of 7.8% under normoxia and 2.4% under hypoxia (GOD concentration: 1.2 µg mL −1 , AQ4N concentration: 1.49 µg mL −1 ).…”

Light-responsive nanomedicine for biophotonic imaging and targeted therapy

“…On the other hand, Zhou et al suggested that low-temperature PTT would be an effective combinational therapy with PTT using a tumor-targeted redox-responsive nanoplatform [33]. This system uses porous hollow Prussian blue NPs (PHPBNs) that have catalase-like activity to catalyze the decomposition of H 2 O 2 in tumors for reoxygenation.…”

“…They showed fast cellular uptake and a killing effect in HepG2 human liver cancer cells with overexpressed CD44 receptors; these effects were also achieved in HepG2 tumor-bearing mice using 808 nm laser irradiation 24 h post-injection. The maximum temperature of the tumor was only 45°C after irradiation, but these NPs effectively suppressed tumor growth in multiple combination strategies based on tumor starvation and PTT [33]. …”