Platinum–Titania Schottky Junction as Nanosonosensitizer, Glucose Scavenger, and Tumor Microenvironment-Modulator for Promoted Cancer Treatment

Abstract

To date, the construction of heterogeneous interfaces between sonosensitizers and other semiconductors or noble metals has aroused increasing attention, owing to an enhanced interface charge transfer, augmented spin–flip, and attenuated activation energy of oxygen. Here, a smart therapeutic nanoplatform is constructed by surface immobilization of glucose oxidase (GOx) onto a TiO2@Pt Schottky junction. The sonodynamic therapy (SDT) and starvation therapy (ST) mediated by TiO2@Pt/GOx (TPG) promote systemic tumor suppression upon hypoxia alleviation in tumor microenvironment. The band gap of TiO2@Pt is outstandingly decreased to 2.9 eV, in contrast to that of pristine TiO2. The energy structure optimization enables a more rapid generation of singlet oxygen (1O2) and hydroxyl radicals (•OH) by TiO2@Pt under ultrasound irradiation, resulting from an enhanced separation of hole–electron pair for redox utilization. The tumorous reactive oxygen species (ROS) accumulation and GOx-mediated glucose depletion facilitate oxidative damage and energy exhaustion of cancer cells, both of which can be tremendously amplified by Pt-catalyzed oxygen self-supply. Importantly, the combinatorial therapy triggers intense immunogenetic cell death, which favors a follow-up suppression of distant tumor and metastasis by evoking antitumor immunity. Collectively, this proof-of-concept paradigm provides an insightful strategy for highly efficient SDT/ST, which possesses good clinical potential for tackling cancer.

External physical field‐driven nanocatalytic cancer therapy

“…[76] (2) Construction of heterostructures and modulation of the energy band structures to enhance ROS generation. [77][78][79] Kang et al prepared a two-dimensional interplanar Z-type heterojunction (FeOCl/FeOOH NSs), the presence of the built-in electric field enhanced the charge transfer, while the catalytically generated O 2 further combines with valence band electrons to generate H 2 O 2 , enhancing the Fenton reaction of iron ions (Figure 2c-f). [80] (3) Adjusting the hydrophobicity and morphological structure of the sonosensitizers can effectively enhance the cavitation effect.…”

“…using photolithography, introduced O 2 vacancies in the BiVO 4 sonosensitizer, enhancing charge separation and alleviating tumor O 2 deprivation by decomposing H 2 O to produce O 2 (Figure 2b). [76] (2) Construction of heterostructures and modulation of the energy band structures to enhance ROS generation [77–79] . Kang et al.…”

Tumor-penetrating nanoplatform with ultrasound “unlocking” for cascade synergistic therapy and visual feedback under hypoxia

“…In brief, the design of an optimized nanoplatform to achieve the full delivery of O 2 and enhanced relevant therapeutic effects should include (i) nanoplatforms for excellent tumor penetration depth and endocytosis, (ii) a controlled O 2 -supplying nanoplatform-vehicle and visually monitored system, and (iii) a nanoplatform-based cascade therapeutic strategy, providing a significant therapeutic effect on hypoxic tumors. Nanoultrasonic biomedicines, including low-diffusion liquid perfluorocarbon (PFC)-based nanodroplets, have been designed for US-activated specific drug release, molecular imaging, SDT, etc [18][19][20][21][22]. Moreover, after US activation, the nanodroplets reach a certain threshold; thus, a large amount of liquid PFC is converted into a gaseous state, and a final rupture occurs due to vibration and expansion, resulting in an ultrasonic cavitation effect, which is also known as acoustic droplet vaporization (ADV), to achieve highly selective drug release and responsive imaging in a pathological tissue [23,24].…”

Defect-Rich Ni–CoO@PEG Porous Hexagonal Nanosheets: Multi-enzyme and Ultrasound Catalysis for Synergistic Anticancer Treatment

“…The intracellular Fenton catalysis is carried out to convert endogenous H 2 O 2 into • OH to realize chemodynamic therapy (CDT), and the catalyst can also be defined as mimic peroxidase (POD). In fact, the H 2 O 2 level is limited (50–100 μM) in the tumor microenvironment (TME), and additional H 2 O 2 supplementation is desired to further promote CDT. − It is known that glucose oxidase (Gox) could catalyze glucose oxidation to provide H 2 O 2 . Glucose is present extensively in all organisms because its metabolism would supply energy for living cells.…”