A Glucose/Oxygen‐Exhausting Nanoreactor for Starvation‐ and Hypoxia‐Activated Sustainable and Cascade Chemo‐Chemodynamic Therapy

Abstract

Fenton reaction‐mediated chemodynamic therapy (CDT) can kill cancer cells via the conversion of H2O2 to highly toxic HO•. However, problems such as insufficient H2O2 levels in the tumor tissue and low Fenton reaction efficiency severely limit the performance of CDT. Here, the prodrug tirapazamine (TPZ)‐loaded human serum albumin (HSA)–glucose oxidase (GOx) mixture is prepared and modified with a metal–polyphenol network composed of ferric ions (Fe3+) and tannic acid (TA), to obtain a self‐amplified nanoreactor termed HSA–GOx–TPZ–Fe3+–TA (HGTFT) for sustainable and cascade cancer therapy with exogenous H2O2 production and TA‐accelerated Fe3+/Fe2+ conversion. The HGTFT nanoreactor can efficiently convert oxygen into HO• for CDT, consume glucose for starvation therapy, and provide a hypoxic environment for TPZ radical‐mediated chemotherapy. Besides, it is revealed that the nanoreactor can significantly elevate the intracellular reactive oxygen species content and hypoxia level, decrease the intracellular glutathione content, and release metal ions in the tumors for metal ion interference therapy (also termed “ion‐interference therapy” or “metal ion therapy”). Further, the nanoreactor can also increase the tumor’s hypoxia level and efficiently inhibit tumor growth. It is believed that this tumor microenvironment‐regulable nanoreactor with sustainable and cascade anticancer performance and excellent biosafety represents an advance in nanomedicine.

Polyphenol‐Containing Nanoparticles: Synthesis, Properties, and Therapeutic Delivery

“…Thanks to the antibacterial, antiinflammatory, antioxidant, and anticancer properties as well as the universal adhesion capability of natural tea polyphenols, polyphenols are fast becoming a popular class of molecules that are attracting more researchers to build various materials for bioimaging, therapeutic delivery, and other biomedical applications. [236][237][238][239][240][241][242][243][244][245][246][247][248][249][250][251] Moreover, inspired by the coordination interactions between various metal ions and polyphenols, researchers have also provided a number of functional MPNs to engineer multifunctional nanosystems. [252][253][254][255][256][257][258][259] Here, we have reviewed the structures and classification of natural polyphenols, the synthesis and properties of the polyphenol-containing nanomaterials, and various biomedical applications of polyphenol-based nanosystems.…”

Recent Advances in Nanomaterial‐Based Nanoplatforms for Chemodynamic Cancer Therapy

“…In another work, the nanoreactor (HGTFT) was employed for combined starvation and hypoxia-activated sustainable and cascade chemo-CDT. [120] The HGTFT is composed of three therapeutic agents, namely the prodrug tirapazamine for CT, GOx for ST, and Febased metal polyphenol network for CDT. The in vitro and in vivo anticancer performance assessments revealed satisfactory anticancer performance, excellent tumor targeting ability, and good biosafety of the HGTFT nanoreactor.…”

Low-Temperature Photothermal Therapy: Strategies and Applications

“…Moreover, glucose oxidase (GOx), which can catalyze glucose, O 2 , and H 2 O into gluconic acid and H 2 O 2 , has been widely used in cancer therapy [ 114 – 116 ]. In the past few years, due to the ability of GOx to achieve cancer starvation, some researchers utilized GOx to realize low-temperature PTT of tumor [ 32 , 117 , 118 ].…”

“…Under mild NIR-II light irradiation, SnSe-PVP not only realized high-performance photothermal conversion for low-temperature PTT but also accomplished pyroelectric dynamic therapy (PEDT). Moreover, in the past few years, CDT which utilizes metal ions (e.g., iron ions) to stimulate Fenton reaction capable of converting H 2 O 2 into highly toxic ·OH to induce cancer cell death has been considered as an appreciated method to conquer cancers [ 116 , 153 , 204 , 205 ]. Considering that elevation of temperature can enhance the Fenton reaction efficiency and ·OH productivity [ 206 , 207 ], She et al fabricated red blood cell (RBC) membrane-coated FeS 2 (FeS 2 @RBCs) with strong absorption at the NIR-II window and Fenton reaction activity to realize the mild PTT-augmented CDT [ 208 ].…”