Dual inhibition of glycolysis and oxidative phosphorylation (OXPHOS) can break the metabolic plasticity of cancer cells to inhibit most energy supply and lead to effective cancer therapy. However, the pharmacokinetic difference among drugs hinders these two inhibitions to realize a uniform temporal and spatial distribution. Herein, we report an aptamer-based artificial enzyme for simultaneous dual inhibition of glycolysis and OXPHOS, which is constructed by arginine aptamer modified carbon-dots-doped graphitic carbon nitride (AptCCN). AptCCN can circularly capture intracellular arginine attribute to the specific binding ability of arginine aptamers to arginine, and further catalyze the oxidation of enriched arginine to nitric oxide (NO) under red light irradiation. In vitro and in vivo experiments showed that arginine depletion and NO stress could inhibit glycolysis and OXPHOS, leading to energy blockage and apoptosis of cancer cells. The presented aptamer-based artificial enzyme strategy provides a new path for cell pathway regulation and synergistic cancer therapy.

Oxygen deficiency is a major obstacle to hypoxic-related cancer theranostics, and developing the oxygen production nanoplatforms received the widespread attention. However, it is remaining a challenge to structure a nanoplatform with hypoxia alleviation effect and imaging-guided cancer radiotherapy. Herein, we present a novel theranostics nanoplatform (Au NPs/UCNPs/WO₃@C) comprising of tungsten trioxide (WO₃) that loaded gold nanoparticles (Au NPs) and up-conversion nanoparticles (UCNPs) for improved photoacoustic (PA) imaging performance in the second near infrared window (NIR-II, 900–1,700 nm). Au NPs/UCNPs/WO₃@C exhibited superior oxygen-generation effect and doxorubicin loading capacity, thus serving as an efficient radiosensitizer for radio-chemo anti-cancer therapy. Importantly, the accumulated Au NPs/UCNPs/WO₃@C in the tumor region led to the increased NIR-II PA imaging signal and the blood oxygen saturation signal, which could enhance radiation sensitivity and accurately guiding cancer radiotherapy to reduce side effects on normal tissues. This study with proof-of-concept confirmed the multifaceted characteristics and encouraging potential of biomimetic Au NPs/UCNPs/WO₃@C for NIR-II PA imaging-guided tumor therapeutics.

Radiotherapy (RT) based on X-ray irradiation is a widely applied cancer treatment strategy in the clinic. However, treating cancer based on RT alone usually results in insufficient radiation energy deposition, which inevitably has serious side effects on healthy parts of the body. Interestingly, high atomic number (high-Z) metal nanocrystals as X-ray sensitizers can reduce the radiation dose effectively due to their high X-ray absorption, which has attracted increased attention in recent years. High-Z metal nanocrystals produce Auger and photoelectrons electrons under X-ray irradiation, which could generate large amounts of reactive oxygen species, and induce cellular damages. The sensitization effect of high-Z metal nanocrystals is closely related with their composition, morphologies, and size, which would strongly impact their performances in the application of cancer imaging and therapy. In this review, we summarize diverse types of X-ray sensitizers such as bismuth, hafnium, gold, and gadolinium for cancer RT and imaging applications. In addition, current challenges and the outlook of RT based on high-Z metal nanocrystals are also discussed.

Multimodal imaging in the second near-infrared window (NIR-II) guided cancer therapy is a highly precise and efficient cancer theranostic strategy. However, it is still a challenge to develop activated NIR-II optical imaging and therapy agents. In this study, we develop a pH-responsive hybrid plasmonic-fluorescent vesicle by self-assembly of amphiphilic plasmonic nanogapped gold nanorod (AuNNR) and fluorescent down-conversion nanoparticles (DCNP) (AuNNR-DCNP Ve), showing remarkable and activated NIR-II fluorescence (FL)/NIR-II photoacoustic (PA) imaging performances. The hybrid vesicle also exhibited superior loading capacity of doxorubicin as a superior drug carrier and efficient radiosensitizer for X-ray-induced radiotherapy. Interestingly, the accumulated hybrid AuNNR-DCNP Ve in the tumor resulted in a recovery of NIR-II FL imaging signal and a variation in NIR-II PA imaging signal. Dual activated NIR-II PA and FL imaging of the hybrid vesicle could trace drug release and precisely guided cancer radiotherapy to ultimately reduce the side effects to healthy tissue.

The promising potential of photodynamic therapy (PDT) has fueled the development of minimally invasive therapeutic approaches for cancer therapy. However, overcoming limitations in PDT efficacy in the hypoxic tumor environment and light penetration depth remains a challenge. We report the engineering of tungsten carbide nanoparticles (W₂C NPs) for 1, 064 nm laser-activated dual-type PDT and combined theranostics. The synthesized W₂C NPs allow the robust generation of dual-type reactive oxygen species, including hydroxyl radicals (type Ⅰ) and singlet oxygen (type Ⅱ), using only single 1, 064 nm laser activation, enabling effective PDT even in the hypoxic tumor environment. The W₂C NPs also possess high photothermal performance under 1, 064 nm laser irradiation, thus enabling synergistically enhanced cancer therapeutic efficacy of PDT and photothermal therapy. Additionally, the photoacoustic and X-ray computed tomography bioimaging properties of W₂C NPs facilitate the integration of tumor diagnosis and therapy. The developed W₂C based theranostic nanoagents increase the generation of reactive oxygen species in hypoxic tumors, improve the light penetration depth, and facilitate combined photothermal therapy and photoacoustic/computed tomography dual-mode bioimaging. These attributes could spur the exploration of transition metal carbides for advanced biomedical applications.