Autophagic blockage by bismuth sulfide nanoparticles inhibits migration and invasion of HepG2 cells.

The biological effects of nanoparticles are of great importance for the in-depth understanding of safety issues in biomedical applications. Induction of autophagy is a cellular response after nanoparticle exposure. Bismuth sulfide nanoparticles (Bi2S3 NPs) are often used as a CT contrast agent because of their excellent photoelectric conversion ability. Yet there has been no previous detailed study other than a cell toxicity assessment. In this study, three types of Bi2S3 NPs with different shapes (Bi2S3 nano rods (BSNR), hollow microsphere Bi2S3 NPs (BSHS) and urchin-like hollow microsphere Bi2S3 NPs (ULBSHS)) were used to evaluatecytotoxicity, autophagy induction, cell migration and invasion in human hepatocellular carcinoma cells (HepG2). Results showed that all three Bi2S3 NPs lead to blockage in autophagic flux, causing p62 protein accumulation. The cell death caused by these Bi2S3 NPs is proved to be autophagy related, rather than related to apoptosis. Moreover, Bi2S3 NPs can reduce the migration and invasion in HepG2 cells in an autophagy-dependent manner. ULBSHS is the most cytotoxic among three Bi2S3 NPs and has the best tumor metastasis suppression. These results demonstrated that, even with relatively low toxicity of Bi2S3 NPs, autophagy blockage may still substantially influence cell fate and thus significantly impact their biomedical applications, and that surface topography is a key factor regulating their biological response.

Biocompatible Fe3+-TA coordination complex with high photothermal conversion efficiency for ablation of cancer cells.

Near-infrared (NIR) light absorbing nanomaterials, which can convert light to heat energy, have great prospects in biomedical applications. In the current work, Fe3+-TA (Tannic Acid) coordination complex formed by simple mixing of tannic acid and FeCl3 solutions was explored as a novel photothermal agent. Due to the strong absorbance in the near-infrared region induced by the coordination effect between TA molecule and Fe3+ ion, the as-prepared Fe3+-TA complex exhibited excellent photothermal performance with high photothermal conversion efficiency of 77.3% and high photothermal stability. Upon the exposure to Fe3+-TA aqueous dispersions with a concentration of 0.125 mg/mL, the cell mortality of HeLa cells was more than 85% after being irradiated for 10 min under NIR light (808 nm, 6 W cm-2). Besides, the Fe3+-TA complex exhibited ultralow cytotoxicity since only biocompatible tannic acid and iron ions were used as raw materials. Therefore, the merits of simple and convenient fabrication method, high photothermal conversion efficiency and excellent biocompatibility endow the high potential of Fe3+-TA complex as a photothermal agent for biomedical applications.

Liquid Exfoliation of Colloidal Rhenium Disulfide Nanosheets as a Multifunctional Theranostic Agent for In Vivo Photoacoustic/CT Imaging and Photothermal Therapy.

Near-infrared light-mediated theranostic agents with superior tissue penetration and minimal invasion have captivated researchers in cancer research in the past decade. Herein, a probe sonication-assisted liquid exfoliation approach for scalable and continual synthesis of colloidal rhenium disulfide nanosheets, which is further explored as theranostic agents for cancer diagnosis and therapy, is reported. Due to high-Z element of Re (Z = 75) and significant photoacoustic effect, the obtained PVP-capped ReS2 nanosheets are evaluated as bimodality contrast agents for computed tomography and photoacoustic imaging. In addition, utilizing the strong near-infrared absorption and ultrahigh photothermal conversion efficiency (79.2%), ReS2 nanosheets could also serve as therapeutic agents for photothermal ablation of tumors with a tumor elimination rate up to 100%. Importantly, ReS2 nanosheets show no obvious toxicity based on the cytotoxicity assay, serum biochemistry, and histological analysis. This work highlights the potentials of ReS2 nanosheets as a single-component theranostic nanoplatform for bioimaging and antitumor therapy.

Natural Humic-Acid-Based Phototheranostic Agent.

Humic acids, a major constituent of natural organic carbon resources, are naturally formed through the microbial biodegradation of animal and plant residues. Due to numerous physiologically active groups (phenol, carboxyl, and quinone), the biomedical applications of humic acid have been already investigated across different cultures for several centuries or even longer. In this work, sodium humate, the sodium salt of humic acid, is explored as phototheranostic agent for light-induced photoacoustic imaging and photothermal therapy based on intrinsic absorption in the near-infrared region. The purified colloidal sodium humate exhibits a high photothermal conversion efficiency up to 76.3%, much higher than that of the majority of state-of-the-art photothermal agents including gold nanorods, Cu9 S5 nanoparticles, antimonene quantum dots, and black phosphorus quantum dots, leading to obvious photoacoustic enhancement in vitro and in vivo. Besides, highly effective photothermal ablation of HeLa tumor is achieved through intratumoral injection. Impressively, sodium humate reveals ultralow toxicity at the cellular and animal levels. This work promises the great potential of humic acids as light-mediated theranostic agents, thus expanding the application scope of traditional humic acids in biomedical field.

Ambient Aqueous Synthesis of Ultrasmall Ni0.85Se Nanoparticles for Noninvasive Photoacoustic Imaging and Combined Photothermal-Chemotherapy of Cancer.

Large-size-induced long-term retention in the body has hampered the translational applications of many reported nanomedicines. Herein, we reported a multifunctional theranostic agent composed of ultrasmall poly(acrylic acid)-functionalized Ni0.85Se nanoparticles (PAA-Ni0.85Se NPs), which were successfully obtained through a facile ambient aqueous precipitation strategy. Without exhibiting any noticeable toxicity, the as-prepared PAA-Ni0.85Se NPs (average diameter of 6.40 ± 1.89 nm) showed considerable absorption in near-infrared (NIR) region and high photothermal conversion efficiency of 54.06%, which could induce remarkable photoacoustic signals for tumor imaging and heat for localized ablation of cancerous cells upon exposure to NIR light. Notably, the ultrasmall PAA-Ni0.85Se NPs, unlike conventional nanomaterials with larger sizes, showed reasonable body clearance within 8 h after intravenous injection. Furthermore, ascribed to protonation process of amino groups in DOX molecules and carboxyl groups in PAA molecules in an acidic microenvironment, the drug-loaded (doxorubicin hydrochloride, DOX·HCl) PAA-Ni0.85Se NPs (PAA-Ni0.85Se-DOX NPs) revealed promoted drug release at acidic pH, which could be useful for acidic tumor microenvironment responsive drug delivery. Evident from the results of cell-killing assay in vitro and tumor treatment study in vivo, PAA-Ni0.85Se-DOX NPs exhibited evident synergistic effects on killing 4T1 breast cancer cells. Thus, this study presents a multifunctional theranostic agent composed of ultrasmall PAA-Ni0.85Se NPs for potential cancer treatment without long-term toxicity concerns.

Controlled synthesis of upconverting nanoparticles/CuS yolk-shell nanoparticles for in vitro synergistic photothermal and photodynamic therapy of cancer cells.

Synergistic photodynamic and photothermal therapy of cancer cells is of considerable scientific and technological interest. In this work, we demonstrate a sacrificial template strategy to fabricate yolk-shell nanoparticles combining upconversion nanoparticles (UCNPs) and CuS nanoparticles. Lanthanide-doped upconversion nanoparticles of NaYF4:30% Yb,1% Nd,0.5% Er@NaYF4:20% Nd (also denoted as UCNPs) have been prepared as 808 nm light excited remote-controlled nanotransducers for in vitro cancer cell treatment. The upconversion fluorescence of the as-prepared UCNPs@CuS yolk-shell nanoparticles is completely quenched under the excitation of an 808 nm laser, which demonstrates that the energy transfer between the UCNPs and CuS is very efficient. In addition, the as-prepared UCNPs@CuS nanoparticles show higher production ability for hydroxyl radicals (˙OH) and singlet oxygen (1O2) compared to CuS hollow nanospheres of similar size. In particular, the excited shell layer (CuS) showed an enhanced photothermal effect while producing reactive oxygen species (ROS) including singlet oxygen (1O2) and hydroxyl radicals (˙OH) after being exposed to near infrared (NIR) light. Thus, the as-prepared UCNPs@CuS yolk-shell nanoparticles exhibited the synergistic effect of photothermal and photodynamic therapy of cancer cells, which resulted in significant cell death after exposure to an 808 nm laser. The synthetic strategy will provide an alternative method to fabricate other UCNP based core-shell nanoparticles for potential and important applications in bionanotechnology including theranostics, multimodal treatment, magnetic resonance imaging-guided photodynamic therapy, etc.

Dopamine-Induced Formation of Ultrasmall Few-Layer MoS2 Homogeneously Embedded in N-Doped Carbon Framework for Enhanced Lithium-Ion Storage.

Molybdenum disulfide with a layered structure and high theoretical capacity is attracting extensive attention for high-performance lithium-ion batteries. In this study, a simple and scalable method by freeze-drying of (NH4)2MoS4 and dopamine mixed solutions along with subsequent calcination is developed to realize the self-assembly of hierarchical MoS2/carbon composite nanosheets via the effect of dopamine-induced morphology transformation, in which ultrasmall few-layer MoS2 nanosheets were homogeneously embedded into a N-doped carbon framework (denoted as MoS2@N-CF). The embedded ultrasmall MoS2 nanosheets (∼5 nm in length) in the composites consist of less than five layers with an expanded interlayer spacing of the (002) plane. When tested as anode materials for rechargeable Li-ion batteries, the obtained MoS2@N-CF nanosheets exhibit outstanding electrochemical performance in terms of high specific capacity (839.2 mAh g-1 at 1 A g-1), high initial Coulombic efficiency (85.2%), and superior rate performance (702.1 mAh g-1 at 4 A g-1). Such intriguing electrochemical performance was attributed to the synergistic effect of uniform dispersion of few-layer MoS2 into the carbon framework, expanded interlayer spacing, and enhanced electronic conductivity in the unique hierarchical architecture. This work provides a simple and effective strategy for the uniform integration of MoS2 with carbonaceous materials to significantly boost their electrochemical performance.

Glucose-Derived Carbonaceous Nanospheres for Photoacoustic Imaging and Photothermal Therapy.

Carbon nanomaterials with small size and unique optical properties have attracted intensive interest for their promising biomedical applications. In this work, glucose-derived carbonaceous nanospheres (CNSs) with high photothermal conversion efficiency up to 35.1% are explored for the first time as a novel carbon-based theranostic agent. Different from most other carbon nanomaterials, the obtained CNSs are highly biocompatible and nontoxic because of their intrinsic hydrophilic property and the use of glucose as raw materials. Under near-infrared laser irradiation (808 nm, 6 W cm(-2)) for 10 min, less than 15% of PC-3M-IE8 cells exposed to CNSs aqueous dispersions (0.16 mg/mL) remained alive. After intravenous administration of CNSs aqueous dispersions into nude mice, the photoacoustic intensity of the tumor region is about 2.5 times higher than that of preinjection. These results indicate that CNSs are suitable for simultaneous photoacoustic imaging and photothermal ablation of cancer cells and can serve as promising biocompatible carbon-based agents for further clinical trials.

Intrinsically Mn2+-Chelated Polydopamine Nanoparticles for Simultaneous Magnetic Resonance Imaging and Photothermal Ablation of Cancer Cells.

Theranostic agents for magnetic resonance imaging (MRI) guided photothermal therapy have attracted intensive interest in cancer diagnosis and treatment. However, the development of biocompatible theranostic agents with high photothermal conversion efficiency and good MRI contrast effect remains a challenge. Herein, PEGylated Mn2+-chelated polydopamine (PMPDA) nanoparticles were successfully developed as novel theranostic agents for simultaneous MRI signal enhancement and photothermal ablation of cancer cells, based on intrinsic manganese-chelating properties and strong near-infrared absorption of polydopamine nanomaterials. The obtained PMPDA nanoparticles showed significant MRI signal enhancement for both in vitro and in vivo imaging. Highly effective photothermal ablation of HeLa cells exposed to PMPDA nanoparticles was then achieved upon laser irradiation for 10 min. Furthermore, the excellent biocompatibility of PMPDA nanoparticles, because of the use of Mn2+ ions as diagnostic agents and biocompatible polydopamine as photothermal agents, was confirmed by a standard MTT assay. Therefore, the developed PMPDA nanoparticles could be used as a promising theranostic agent for MRI-guided photothermal therapy of cancer cells.