Bioimaging and prospects of night pearls-based persistence phosphors in cancer diagnostics.

Inorganic persistent phosphors feature great potential for cancer diagnosis due to the long luminescence lifetime, low background scattering, and minimal autofluorescence. With the prominent advantages of near-infrared light, such as deep penetration, high resolution, low autofluorescence, and tissue absorption, persistent phosphors can be used for deep bioimaging. We focus on highlighting inorganic persistent phosphors, emphasizing the synthesis methods and applications in cancer diagnostics. Typical synthetic methods such as the high-temperature solid state, thermal decomposition, hydrothermal/solvothermal, and template methods are proposed to obtain small-size phosphors for biological organisms. The luminescence mechanisms of inorganic persistent phosphors with different excitation are discussed and effective matrixes including galliumate, germanium, aluminate, and fluoride are explored. Finally, the current directions where inorganic persistent phosphors can continue to be optimized and how to further overcome the challenges in cancer diagnosis are summarized.

Sono-blasting Triggered Cascading-Amplification of Oxidative Stress for Enhanced Interventional Therapy of Hepatocellular Carcinoma.

Interventional therapy is widely regarded as a highly promising treatment approach for nonsurgical liver cancer. However, the development of drug resistance and tolerance to hypoxic environments after embolization can lead to increased angiogenesis, enhanced tumor cell stemness, and greater invasiveness, resulting in metastasis and recurrence. To address these challenges, a novel approach involving the use of lecithin and DSPE-PEG comodified Ca2+ loaded (NH4)2S2O8 (LDCNSO) drug in combination with transcatheter arterial embolization (TAE) has been proposed. The sono-blasting effect of LDCNSO under ultrasound triggers a cascading amplification of oxidative stress, by releasing sulfate radical (·SO4-), hydroxyl radical (·OH), and superoxide (·O2-), inducing Ca2+ overload, and reducing glutathione (GSH) levels, which eventually leads to apoptosis. LDCNSO alongside TAE has demonstrated remarkable therapeutic efficacy in the rabbit orthotopic cancer model, resulting in significant inhibition of tumor growth. This research provides valuable insights for the effective treatment of orthotopic tumors.

Novel Spatially Asymmetric Copper Bismuthate-Mediated Augmentation of Energy Conversion to Realize "Three-Step" Tumor Suppression.

The generally undesirable bandgap and electron-hole complexation of inorganic sonosensitizers limit the efficiency of reactive oxygen species (ROS) generation, affecting the effectiveness of sonodynamic therapy (SDT). Comparatively, the novel polyvinylpyrrolidone-modified copper bismuthate (PCBO) sonosensitizers are manufactured for a "three-step" SDT promotion. In brief, first, the strong hybridization between Bi 6s and O 2p orbitals in PCBO narrows the bandgap (1.83 eV), facilitating the rapid transfer of charge carriers. Additionally, nonequivalent [CuO4]6- layers reduce crystal symmetry, confer PCBO unique piezoelectricity, and improve electron-hole separation under ultrasonic (US) excitation. This allows PCBO to convert US energy into chemical energy to produce ROS, achieving the accumulation of abundant ROS, resulting in apoptosis and tumor suppression. Concurrently, PCBO also acts as a glutathione scavenger to reduce tumor antioxidant capacity and improve efficacy. To the best of authors understanding, this study reveals PCBO as an innovative piezoelectric sonosensitizer and provides a meaningful paradigm for designing energy conversion strategies for tumor suppression.

Selenium Vacancy Engineering Using Bi2Se3 Nanodots for Boosting Highly Efficient Photonic Hyperthermia.

Despite bismuth-based energy conversion nanomaterials having attracted extensive attention for nanomedicine, the nanomaterials suffer from major shortcomings including low tumor accumulation, long internal retention time, and undesirable photothermal conversion efficiency (PCE). To combat these challenges, bovine serum albumin and folic acid co-modified Bi2Se3 nanomedicine with rich selenium vacancies (abbreviated as VSe-BS) was fabricated for the second near-infrared (NIR-II) light-triggered photonic hyperthermia. More importantly, selenium vacancies on the crystal planes (0 1 5) and (0 1 11) of VSe-BS with similar formation energies could be distinctively observed via aberration-corrected scanning transmission electron microscopy images. The defect engineering endows VSe-BS with enhanced conductivity, making VSe-BS possess outstanding PCE (54.1%) in the NIR-II biowindow and desirable photoacoustic imaging performance. Tumor ablation studies indicate that VSe-BS possesses satisfactory therapeutic outcomes triggered by NIR-II light. These findings give rise to inspiration for further broadening the biological applications of defect engineering bismuth-based nanomaterials.

Energy-converting biomaterials for cancer therapy: Category, efficiency, and biosafety.

Energy-converting biomaterials (ECBs)-mediated cancer-therapeutic modalities have been extensively explored, which have achieved remarkable benefits to overwhelm the obstacles of traditional cancer-treatment modalities. Energy-driven cancer-therapeutic modalities feature their distinctive merits, including noninvasiveness, low mammalian toxicity, adequate therapeutic outcome, and optimistical synergistic therapeutics. In this advanced review, the prevailing mainstream ECBs can be divided into two sections: Reactive oxygen species (ROS)-associated energy-converting biomaterials (ROS-ECBs) and hyperthermia-related energy-converting biomaterials (H-ECBs). On the one hand, ROS-ECBs can transfer exogenous or endogenous energy (such as light, radiation, ultrasound, or chemical) to generate and release highly toxic ROS for inducing tumor cell apoptosis/necrosis, including photo-driven ROS-ECBs for photodynamic therapy, radiation-driven ROS-ECBs for radiotherapy, ultrasound-driven ROS-ECBs for sonodynamic therapy, and chemical-driven ROS-ECBs for chemodynamic therapy. On the other hand, H-ECBs could translate the external energy (such as light and magnetic) into heat for killing tumor cells, including photo-converted H-ECBs for photothermal therapy and magnetic-converted H-ECBs for magnetic hyperthermia therapy. Additionally, the biosafety issues of ECBs are expounded preliminarily, guaranteeing the ever-stringent requirements of clinical translation. Finally, we discussed the prospects and facing challenges for constructing the new-generation ECBs for establishing intriguing energy-driven cancer-therapeutic modalities. This article is categorized under: Nanotechnology Approaches to Biology >Nanoscale Systems in Biology.

Engineering Gadolinium-Integrated Tellurium Nanorods for Theory-Oriented Photonic Hyperthermia in the NIR-II Biowindow.

Near-infrared (NIR) light-triggered hyperthermia has exhibited promising prospects in oncology therapy due to the unique merits including minimal invasiveness, monitorable, excellent therapeutic effect, and negligible side effects. Especially, the second NIR biowindow (NIR-II, 1000-1700 nm) with less absorbance and scattering by skin tissue, and deep tissue penetration, has received extensive attention for photonic hyperthermia. Unfortunately, the dissatisfactory photothermal conversion efficiency (PCE) and cumbersome preparation process of photo-driven heat conversion nanomaterials seriously hamper the future clinical application. To combat the aforementioned challenges, high imaging performance and desired therapeutic outcome 1D nanorods are constructed based on gadolinium-integrated tellurium nanorods (Te-Gd). In this system, magnetic resonance (MR) imaging and X-ray computed tomography (CT) imaging-guided photonic hyperthermia can be easily implemented in cooperation with Te-Gd. Importantly, Te-Gd possesses high PCE (41%) in the NIR-II biowindow because the transition of the excited electron can easily occur from the valence band (VB) to the conduction band (CB) on (1 0 1) and (1 0 2) crystal planes. Furthermore, the distinctive photostability, high tumor accumulation, as well as low systemic adverse effects of Te-Gd guarantee the potential in the clinic.

Ultrasmall Ag2Te Quantum Dots with Rapid Clearance for Amplified Computed Tomography Imaging and Augmented Photonic Tumor Hyperthermia.

With the fast development of nanomedicine, the imaging-guided and photo-induced cancer monotherapies can efficiently eliminate tumor lesions, which are strongly dependent on the construction of versatile theranostic nanoplatforms. Among diverse photo-converting nanoplatforms, silver chalcogenide nanoparticles feature high biocompatibility, narrow band gaps, and tunable optical properties, yet Ag2Te-based nanosystems are still at a proof-of-concept stage, and the exploration of Ag2Te-based nanosystems suitable for photonic tumor hyperthermia is challenging. Herein, we report on the construction of versatile ultrasmall Ag2Te quantum dots (QDs) via a facile biomineralization strategy. Especially, these Ag2Te QDs with negligible toxicity and excellent biocompatibility were developed for X-ray computed tomography (CT) imaging-guided photonic tumor hyperthermia by near-infrared (NIR) activation. The fabricated Ag2Te QDs exhibited a high tumor suppression rate (94.3%) on 4T1 breast tumor animal models due to the high photothermal-conversion efficiency (50.5%). Mechanistically, Ag2Te QDs were promising potential CT imaging agents for imaging guidance and monitoring during photonic hyperthermia. Importantly, Ag2Te QDs were rapidly eliminated from the body via feces and urine because of their ultrasmall sizes. This work not only broadens the biomedical applications of silver chalcogenide-based theranostic nanosystems but also provides the paradigm of theranostic nanosystems with a photonic tumor hyperthermia effect and outstanding contrast enhancement of high-performance CT imaging.

A highly active (102) surface-induced rapid degradation of a CuS nanotheranostic platform for in situ T1-weighted magnetic resonance imaging-guided synergistic therapy.

Polyvinylpyrrolidone-modified CuS nanocrystals (CuS NCs) with high photothermal conversion efficiency (46%) and pH and near-infrared (NIR) light-triggered degradation properties are a promising nanotheranostic platform for in situ magnetic resonance imaging (MRI)-guided synergistic photothermal and photodynamic therapy. On the one hand, the (102) surface of CuS NCs has a small bandgap based on density functional theory, which leads to high photothermal conversion efficiency. On the other hand, the S vacancy formation energy of the (102) surface is favourable. On entry into tumor cells through endocytosis, the S2- ions on the (102) surface of CuS NCs can be easily oxidized under the tumor microenvironment and 808 nm laser irradiation; then, a large amount of Cu+ ions can be released from CuS NCs and accelerate the degradation of nanocrystals. Cu+ ions can generate reactive oxygen species (ROS) under the tumor microenvironment and 808 nm laser irradiation. Meanwhile, the oxidation product Cu2+ ions can be generated from the oxidized Cu+ ions and applied for in situ T1-weighted magnetic resonance imaging. Moreover, the biodegradable CuS NCs possess a high tumor uptake and can be rapidly excreted with a low long-term retention/toxicity. Therefore, degradable and multifunctional CuS NCs are a safe and efficient candidate for the diagnosis and treatment of cancer.

Renal Clearable Bi-Bi2S3 Heterostructure Nanoparticles for Targeting Cancer Theranostics.

Recent development of precise nanomedicine has aroused an overwhelming interest in integration of diagnosis and treatment for cancers. Designing renal-clearable and targeting nanoparticles (NPs) has specific cancer theranostic implications and remains a challenging task. In this work, the ultrasmall folic acid (FA) and bovine serum albumin-modified Bi-Bi2S3 heterostructure nanoparticles NPs (Bi-Bi2S3/BSA&FA NPs) with excellent computed tomography (CT) and photoacoustic imaging abilities and outstanding photothermal performances were synthesized in an aqueous phase route via a simple method. Bi-Bi2S3/BSA&FA NPs have the following criteria: (i) Bi-Bi2S3/BSA&FA NPs with heterostructure possess better stability than Bi NPs and higher Bi content than Bi2S3 NPs, which are conducive to the enhancement of CT imaging effect; (ii) Bi-Bi2S3/BSA&FA NPs with FA molecules on the surface could target the tumor site effectively; (iii) Bi-Bi2S3/BSA&FA NPs could inhibit tumor growth effectively under 808 nm laser irradiation; (iv) ultrasmall Bi-Bi2S3/BSA&FA NPs could be cleared through kidney and liver within a reasonable time, avoiding a long-term retention/toxicity. Therefore, the renal clearable Bi-Bi2S3/BSA&FA NPs are a promising agent for targeting cancer theranostics.

Ultrafast synthesis of ultrasmall polyethylenimine-protected AgBiS2 nanodots by "rookie method" for in vivo dual-modal CT/PA imaging and simultaneous photothermal therapy.

Developing a biocompatible nanotheranostic platform integrating diagnostic and therapeutic functions is a great prospect for cancer treatment. However, it is still a great challenge to synthesize nanotheranostic agents using an ultra-facile method. In the research reported here, ultrasmall polyethylenimine-protected silver bismuth sulfide (PEI-AgBiS2) nanodots were successfully synthesized using an ultra-facile and environmentally friendly strategy (1 min only at room temperature), which could be described as a "rookie method". PEI-AgBiS2 nanodots show good monodispersity and biocompatibility. For the first time, PEI-AgBiS2 nanodots were reported as a powerful and safe nanotheranostic agent for cancer treatment. PEI-AgBiS2 nanodots exhibit excellent computed tomography (CT) and photoacoustic (PA) dual-modal imaging ability, which could effectively guide photothermal cancer therapy. Furthermore, PEI-AgBiS2 nanodots exhibit a high photothermal conversion efficiency (η = 35.2%). The photothermal therapy (PTT) results demonstrated a highly efficient tumor ablation ability. More importantly, the blood biochemistry and histology analyses verify that the PEI-AgBiS2 nanodots have negligible long-term toxicity. This work highlights that PEI-AgBiS2 nanodots produced using this extremely effective method are a high-performance and safe PTT agent. These findings open a new gateway for synthesizing nanotheranostic agents by using this ultra-facile method in the future.

Simple construction of Cu2-xS:Pt nanoparticles as nanotheranostic agent for imaging-guided chemo-photothermal synergistic therapy of cancer.

Synergistic therapy has attracted intense attention in medical treatment because it can make up for the disadvantages of single therapy and greatly improve the efficacy of cancer treatment. However, it remains a challenge to build a simple system to achieve synergistic therapy. In this study, X-ray computed tomography (CT) imaging-guided chemo-photothermal synergistic therapy can be easily achieved by simple construction of Cu2-xS:Pt(0.3)/PVP nanoparticles (NPs). Cu2-xS:Pt(0.3)/PVP NPs can passively accumulate within the tumor sites, thus ensuring that many Cu2-xS:Pt(0.3)/PVP NPs are brought into the tumor cells, which can be confirmed by the results of cellular uptake, imaging, and nanoparticle biodistribution. It can be verified that the platinum ions can be released from Cu2-xS:Pt(0.3)/PVP NPs under 808 nm laser irradiation. Simultaneously, Pt(iv) ions are reduced to Pt(ii) ions by excess glutathione and then, they exhibit chemo-anticancer activities. In addition, Cu2-xS:Pt(0.3)/PVP NPs can be used as an effective photothermal agent. The results demonstrate that the efficient tumor growth inhibition effect can be realized from the mice treated with Cu2-xS:Pt(0.3)/PVP NPs under 808 nm laser irradiation by chemo-photothermal synergistic therapy. Furthermore, Cu2-xS:Pt(0.3)/PVP NPs can be thoroughly cleared through feces in a short time, showing high biosafety for further potential clinical translations.

Protection by the Total Flavonoids from Rosa laevigata Michx Fruit against Lipopolysaccharide-Induced Liver Injury in Mice via Modulation of FXR Signaling.

We previously reported the effects of the total flavonoids (TFs) from Rosa laevigata Michx fruit against carbon tetrachloride-induced liver damage, non-alcoholic fatty liver disease, and liver ischemia-reperfusion injury. However, there have been no papers reporting the role of R. laevigata TFs against lipopolysaccharide (LPS)-induced liver injury. In this paper, liver injury in mice was induced by LPS, and R. Laevigata extract was intragastrically administered to the mice for 7 days. Biochemical parameters in serum and liver tissue were examined, and pathological changes were observed by transmission electron microscopy, hematoxylin and eosin (H&E) and Oil Red O staining. The results showed that the TFs markedly reduced serum ALT (alanine transferase), AST (aspartate transaminase), TG (total triglyceride), and TC (total cholesterol) levels and relative liver weights and improved liver pathological changes. In addition, the TFs markedly decreased tissue MDA (malondialdehyde) level and increased the levels of SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase). A mechanistic study showed that the TFs significantly increased the expression levels of Nrf2 (nuclear erythroid factor2-related factor 2), HO-1 (heme oxygenase-1), NQO1 (NAD(P)H dehydrogenase (quinone 1), GCLC (glutamate-cysteine ligase catalytic subunit), and GCLM (glutamate-cysteine ligase regulatory subunit) and decreased Keap1 (Kelch-like ECH-associated protein 1) level by activating FXR (farnesoid X receptor) against oxidative stress. Furthermore, the TFs markedly suppressed the nuclear translocation of NF-κB (nuclear factor-kappa B) and subsequently decreased the expression levels of IL (interleukin)-1β, IL-6, HMGB-1 (high -mobility group box 1), and COX-2 (cyclooxygenase-2) by activating FXR and FOXO3a (forkhead box O3) against inflammation. Besides, the TFs obviously reduced the expression levels of SREBP-1c (sterol regulatory element-binding proteins-1c), ACC1 (acetyl-CoA carboxylase-1), FASN (fatty acid synthase), and SCD1 (stearoyl-coenzyme A desaturase 1), and improved CPT1 (carnitine palmitoyltransferase 1) level by activating FXR to regulate lipid metabolism. Our results suggest that TFs exhibited protective effect against LPS-induced liver injury by altering FXR-mediated oxidative stress, inflammation, and lipid metabolism, and should be developed as an effective food and healthcare product for the therapy of liver injury in the future.

Multifunctional Cu-Ag2S nanoparticles with high photothermal conversion efficiency for photoacoustic imaging-guided photothermal therapy in vivo.

Photothermal therapy (PTT) has attracted increasing interest and become widely used in cancer therapy owing to its noninvasiveness and low level of systemic adverse effects. However, there is an urgent need to develop biocompatible and multifunctional PTT agents with high photothermal conversion efficiency. Herein, biocompatible Cu-Ag2S/PVP nanoparticles (NPs) with strong near-infrared absorption and high photothermal conversion efficiency were successfully synthesized for high-performance photoacoustic (PA) imaging-guided PTT in vivo. The novel Cu-Ag2S/PVP NPs feature high photothermal conversion efficiency (58.2%) under 808 nm light irradiation, noticeably higher than those of most reported PTT agents. Because of their good dispersibility, Cu-Ag2S/PVP NPs passively accumulate within tumors via the enhanced permeability and retention effect, which can be confirmed by PA imaging, photothermal performance, and biodistribution in vivo. Furthermore, Cu-Ag2S/PVP NPs are thoroughly cleared through feces and urine within seven days, indicating a high level of biosafety for further potential clinical translation.

PEGylated GdF3:Fe Nanoparticles as Multimodal T1/T2-Weighted MRI and X-ray CT Imaging Contrast Agents.

Contrast agents for multimodal imaging are in high demand for cancer diagnosis. To date, integration of T1/T2-weighted magnetic resonance imaging (MRI) and X-ray computed tomography (CT) imaging capabilities in one system to obtain an accurate diagnosis still remains challenging. In this work, biocompatible PEGylated GdF3:Fe nanoparticles (PEG-GdF3:Fe NPs) were reasonable designed and synthesized as multifunctional contrast agents for efficient T1/T2-weighted MRI and X-ray CT multimodal imaging. Owing to the enhanced permeability and retention effect in vivo, strong T1 contrast, evident T2 contrast, and X-ray CT signals in a tumor lesion can be observed after intravenous injection of PEG-GdF3:Fe NPs. Therefore, PEG-GdF3:Fe NPs could be used as potential multimodal contrast agents for cancer diagnosis.