Zhao Guo

XANES and SR-TXM were used to investigate the fates of MoS ₂ -PVP nanosheets in vivo and in vitro .

Peroxynitrite (ONOO⁻), the reaction product derived from nitric oxide (NO) and superoxide (O₂^−•), is a potent oxidizing and nitrating agent that modulates complex biological processes and promotes cell death. Therefore, it can be expected that the overproduction of ONOO⁻ in tumors can be an efficient approach in cancer therapy. Herein, a multifunctional X‐ray‐controlled ONOO⁻ generation platform based on scintillating nanoparticles (SCNPs) and UV‐responsive NO donors Roussin's black salt is reported, and consequently the mechanism of their application in enhanced therapeutic efficacy of radiotherapy is illustrated. Attributed to the radioluminescence and high X‐ray‐absorbing property of SCNPs, the nanocomposite can produce NO and O₂^−• simultaneously when excited by X‐ray irradiation. Such simultaneous release of NO and O₂^−• ensures the efficient X‐ray‐controlled generation of ONOO⁻ in tumors. Meanwhile, the application of X‐rays as the excitation source can achieve better penetration depth and induce radiotherapy in this nanotherapeutic platform. It is found that the X‐ray‐controlled ONOO⁻‐generation platform can efficiently improve the radiotherapy efficiency via directly damaging DNA, downregulating the expression of the DNA‐repair enzyme, and overcoming the hypoxia‐associated resistance in radiotherapy. Therefore, this SCNP‐based platform may provide a new combinatorial strategy of ONOO⁻ and radiotherapy to improve cancer treatment.

Chemotherapy resistance remains a major hurdle for cancer therapy in clinic due to poor cellular uptake, insufficient intracellular release of drugs. Herein, an intelligent, multifunctional MoS2 nanotheranostic (MoS2-PEI-HA) ingeniously decorating with biodegradable hyaluronic acid (HA) assisted by polyethyleneimine (PEI) is reported to combat drug-resistant breast cancer (MCF-7-ADR) after loading with chemotherapy drug doxorubicin (DOX). The HA can not only target CD44-overexpressing MCF-7-ADR, but also be degraded by hyaluronidase (HAase) that is concentrated in the tumor microenvironment and thus to accelerate doxorubicin (DOX) release. Furthermore, the MoS2 with strong near infrared (NIR) photothermal conversion ability can also promote release of DOX in the acidic tumor environment at a mild 808 nm laser irradiation, achieving a superior anti-tumor activity based on the programmed response to HAase and NIR laser actuator. Most importantly, HA targeting combined with mild NIR laser stimuli rather than using hyperthermia can potently down-regulate the expression of drug-resistance related P-glycoprotein (P-gp), resulting in greatly enhanced intracellular drug accumulation, thus achieving drug resistance reversal. After labeled with 64Cu by a simple chelation strategy, the MoS2 was employed for real-time photon emission computed tomography (PET) imaging of MCF-7-ADR tumor in vivo. This multifunctional nanoplatform paves a new avenue for PET imaging guided spatial-temporal controlled accurate therapy of drug-resistant cancer.

Developing an effective theranostic nanoplatform remains a great challenge for cancer diagnosis and treatment. Here, BiOI@Bi₂S₃@BSA (bovine serum albumin) semiconductor heterojunction nanoparticles (SHNPs) for triple‐combination radio/photodynamic/photothermal cancer therapy and multimodal computed tomography/photoacoustic (CT/PA) bioimaging are reported. On the one hand, SHNPs possess strong X‐ray attenuation capability since they contain high‐Z elements, and thus they are anticipated to be a very competent candidate as radio‐sensitizing materials for radiotherapy enhancement. On the other hand, as a semiconductor, the as‐prepared SHNPs offer an extra approach for reactive oxygen species generation based on electron–hole pair under the irradiation of X‐ray through the photodynamic therapy process. This X‐ray excited photodynamic therapy obviously has better penetration depth in bio‐tissue. What's more, the SHNPs also possess well photothermal conversion efficiency for photothermal therapy, because Bi₂S₃ is a thin band semiconductor with strong near‐infrared absorption that can cause local overheat. In vivo tumor ablation studies show that synergistic radio/photodynamic/photothermal therapy achieves more significant therapeutic effect than any single treatment. In addition, with the strong X‐ray attenuation and high near‐infrared absorption, the as‐obtained SHNPs can also be applied as a multimodal contrast agent in CT/PA imaging.

Radioresistance is one of the undesirable impediments in hypoxic tumors, which sharply diminishes the therapeutic effectiveness of radiotherapy and eventually results in the failure of their treatments. An attractive strategy for attenuating radioresistance is developing an ideal radiosensitization system with appreciable radiosensitization capacity to attenuate tumor hypoxia and reinforce radiotherapy response in hypoxic tumors. Therefore, we describe the development of Gd-containing polyoxometalates-conjugated chitosan (GdW₁₀@CS nanosphere) as a radiosensitization system for simultaneous extrinsic and intrinsic radiosensitization, by generating an overabundance of cytotoxic reactive oxygen species (ROS) using high-energy X-ray stimulation and mediating the hypoxia-inducible factor-1a (HIF-1a) siRNA to down-regulate HIF-1α expression and suppress broken double-stranded DNA self-healing. Most importantly, the GdW₁₀@CS nanospheres have the capacity to promote the exhaustion of intracellular glutathione (reduced GSH) by synergy W⁶⁺-triggered GSH oxidation for sufficient ROS generation, thereby facilitating the therapeutic efficiency of radiotherapy. As a result, the as-synthesized GdW₁₀@CS nanosphere can overcome radioresistance of hypoxic tumors through a simultaneous extrinsic and intrinsic strategy to improve radiosensitivity. We have demonstrated GdW₁₀@CS nanospheres with special radiosensitization behavior, which provides a versatile approach to solve the critical radioresistance issue of hypoxic tumors.

Low water solubility, extensive metabolism, and drug resistance are the existing unavoidable disadvantages of the insoluble drug curcumin in biomedical applications. Herein, we employed d-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-functionalized near-infrared (NIR)-triggered photothermal mesoporous nanocarriers with bamboo charcoal nanoparticles (TPGS-BCNPs) to load and deliver curcumin for improving its bioavailability. This system could considerably increase the accumulation of curcumin in cancer cells for enhanced curcumin bioavailability via simultaneously promoting the cellular internalization of the as-synthesized composite (TPGS-BCNPs@curcumin) by the size effect of NPs and considerably triggering controlled curcumin release from TPGS-BCNPs@curcumin by NIR stimulation and reducing efflux of curcumin by the P-glycoprotein (P-gp) inhibition of TPGS, so as to enhance the therapeutic effect of curcumin and realize a better chemo-photothermal synergetic therapy in vitro and in vivo. Besides cancer therapy, studies indicated that curcumin and some carbon materials could be used as radical scavengers that play an important role in the radioprotection of normal cells. Hence, we also investigated the free-radical-scavenging ability of the TPGS-BCNPs@curcumin composite in vitro to preliminarily evaluate its radioprotection ability for healthy tissues. Therefore, our work provides a multifunctional delivery system for curcumin bioavailability enhancement, chemo-photothermal synergetic therapy of cancer, and radioprotection of healthy tissues.