Ultra small gold nanoclusters supported on two-dimensional bismuth selenium nanosheets for synergistic photothermal and photodynamic tumor therapy.

Two-dimensional (2D) bismuth selenium (Bi2Se3) nanosheets have exceptional surface area and superior surface modification capabilities, facilitating the effective loading of nanoprobes, metal particles, and other substances. Additionally, thiolated ultrasmall gold nanoclusters (Au NCs), distinguished by their high photoluminescent activity and modulatable surface charges, enable efficient loading onto the 2D Bi2Se3 surfaces. In this study, we successfully prepared Bi2Se3 nanosheets by sonication-assisted liquid phase exfoliation and loaded Au clusters on their surface through an amide bond reaction. The loading of Au NCs significantly augments the photothermal and photocatalytic capabilities of Bi2Se3 nanosheets and exhibits obvious anti-cancer therapeutic effects through in vitro and in vivo experiments. In summary, the as-prepared AuNC@Bi2Se3 nanocomposites showed combined near-infrared light-initiated photothermal/photodynamic therapy (PTT/PDT) against tumors, demonstrating their potential as novel theranostic agents for biomedical applications.

Smart Nanoplatforms Responding to the Tumor Microenvironment for Precise Drug Delivery in Cancer Therapy.

The tumor microenvironment (TME) is a complex and dynamic entity, comprising stromal cells, immune cells, blood vessels and extracellular matrix, which is intimately associated with the occurrence and development of cancers, as well as their therapy. Utilizing the shared characteristics of tumors, such as an acidic environment, enzymes and hypoxia, researchers have developed a promising cancer therapy strategy known as responsive release of nano-loaded drugs, specifically targeted at tumor tissues or cells. In this comprehensive review, we provide an in-depth overview of the current fundamentals and state-of-the-art intelligent strategies of TME-responsive nanoplatforms, which include acidic pH, high GSH levels, high-level adenosine triphosphate, overexpressed enzymes, hypoxia and reductive environment. Additionally, we showcase the latest advancements in TME-responsive nanoparticles. In conclusion, we thoroughly examine the immediate challenges and prospects of TME-responsive nanopharmaceuticals, with the expectation that the progress of these targeted nanoformulations will enable the exploitation, overcoming or modulation of the TME, ultimately leading to significantly more effective cancer therapy.

NIR-II Light-Driven Genetically Engineered Exosome Nanocatalysts for Efficient Phototherapy against Glioblastoma.

Glioblastoma (GBM) poses a significant therapeutic challenge due to its invasive nature and limited drug penetration through the blood-brain barrier (BBB). In response, here we present an innovative biomimetic approach involving the development of genetically engineered exosome nanocatalysts (Mn@Bi2Se3@RGE-Exos) for efficient GBM therapy via improving the BBB penetration and enzyme-like catalytic activities. Interestingly, a photothermally activatable multiple enzyme-like reactivity is observed in such a nanosystem. Upon NIR-II light irradiation, Mn@Bi2Se3@RGE-Exos are capable of converting hydrogen peroxide into hydroxyl radicals, oxygen, and superoxide radicals, providing a peroxidase (POD), oxidase (OXD), and catalase (CAT)-like nanocatalytic cascade. This consequently leads to strong oxidative stresses to damage GBM cells. In vitro, in vivo, and proteomic analysis further reveal the potential of Mn@Bi2Se3@RGE-Exos for the disruption of cellular homeostasis, enhancement of immunological response, and the induction of cancer cell ferroptosis, showcasing a great promise in anticancer efficacy against GBM with a favorable biosafety profile. Overall, the success of this study provides a feasible strategy for future design and clinical study of stimuli-responsive nanocatalytic medicine, especially in the context of challenging brain cancers like GBM.

Recent Advances of Emerging Metal-Containing Two-Dimensional Nanomaterials in Tumor Theranostics.

In recent years, metal-containing two-dimensional (2D) nanomaterials, among various 2D nanomaterials have attracted widespread attention because of their unique physical and chemical properties, especially in the fields of biomedical applications. Firstly, the review provides a brief introduction to two types of metal-containing 2D nanomaterials, based on whether metal species take up the major skeleton of the 2D nanomaterials. After this, the synthetical approaches are summarized, focusing on two strategies similar to other 2D nanomaterials, top-down and bottom-up methods. Then, the performance and evaluation of these 2D nanomaterials when applied to cancer therapy are discussed in detail. The specificity of metal-containing 2D nanomaterials in physics and optics makes them capable of killing cancer cells in a variety of ways, such as photodynamic therapy, photothermal therapy, sonodynamic therapy, chemodynamic therapy and so on. Besides, the integrated platform of diagnosis and treatment and the clinical translatability through metal-containing 2D nanomaterials is also introduced in this review. In the summary and perspective section, advanced rational design, challenges and promising clinical contributions to cancer therapy of these emerging metal-containing 2D nanomaterials are discussed.

Preparation of expandable vertically aligned carbon nanotube arrays/polydimethylsiloxane membrane by a modular splicing method and its application in in situ ethanol recovery from ethanol fermentation.

Aligned carbon nanotube (CNT) arrays have been widely used in the preparation of polymer composites. CNT arrays are commonly prepared by chemical vapor deposition (CVD) in a high temperature tubular furnace, and the areas of the aligned CNT/polymer membranes prepared are relatively small (<30 cm2) due to the limitation of the inner diameter of the furnace, which limits its practical application in the field of membrane separation. Herein, the vertically aligned CNT arrays/polydimethylsiloxane (PDMS) membrane with large and expandable area was prepared by a modular splicing method for the first time, with a maximum area of 144 cm2. The addition of CNT arrays with openings at both ends significantly improved the pervaporation performance of the PDMS membrane for ethanol recovery. At 80 °C, the flux (671.6 g m-2 h-1) and separation factor (9.0) of CNT arrays/PDMS membrane were increased by 435.12% and 58.52%, respectively, compared with those of the PDMS membrane. Furthermore, the expandable area enabled the CNT arrays/PDMS membrane to couple with fed-batch fermentation for pervaporation for the first time, which increased the ethanol yield (0.47 g g-1) and productivity (2.34 g L-1 h-1) by 9.3% and 4.9% respectively compared with batch fermentation. Besides, the flux (135.47-166.79 g m-2 h-1) and separation factor (8.83-9.21) of CNT arrays/PDMS membrane remained stable in this process, indicating that this membrane has the potential to be applied in industrial bioethanol production. This work provides a new idea for the preparation of large-area aligned CNT/polymer membranes, and also opens up a new direction for the application of large-area aligned CNT/polymer membranes.

Facile Synthesis of Monodispersed Titanium Nitride Quantum Dots for Harmonic Mode-Locking Generation in an Ultrafast Fiber Laser.

As a member of the transition metal nitride material family, titanium nitride (TiN) quantum dots (QDs) have attracted great attention in optical and electronic fields because of their excellent optoelectronic properties and favorable stability. Herein, TiN QDs were synthesized and served as a saturable absorber (SA) for an ultrafast fiber laser. Due to the strong nonlinear optical absorption characteristics with a modulation depth of ~33%, the typical fundamental mode-locked pulses and harmonics mode-locked pulses can be easily obtained in an ultrafast erbium-doped fiber laser with a TiN-QD SA. In addition, at the maximum pump power, harmonic mode-locked pulses with a repetition rate of ~1 GHz (164th order) and a pulse duration of ~1.45 ps are achieved. As far as we know, the repetition rate is the highest in the ultrafast fiber laser using TiN QDs as an SA. Thus, these experimental results indicate that TiN QDs can be considered a promising material, showing more potential in the category of ultrafast laser and nonlinear optics.

Nitroreductase-Induced Aggregation of Gold Nanoparticles for "Off-On" Photoacoustic Imaging of Tumor Hypoxia.

Hypoxia is an important phenomenon due to insufficient oxygen supply in tumor tissue, and nitroreductase (NTR) is a characteristic enzyme used for evaluating hypoxia level in tumors. In this work, we designed a smart gold nanoparticle (AuNPs), modified by 16-mercaptoundecanoic acid (MHDA) and hypoxia-responsive 11-(2-nitro-1H-imidazol-1-yl)undecane-1-thiol (NI) ligand, that responds to the hypoxic environment in tumor sites. With proper surface ligand composition, the responsive nanoprobe exhibited aggregation through the bioreduction of the nitro group on NI ligands under hypoxic conditions and the UV-vis absorption peak maximum would shift to 630 nm from 530 nm, which acts as an "off-on" contrast agent for tumor hypoxic photoacoustic (PA) imaging. In vitro and in vivo experiments revealed that AuNPs@MHDA/NO2 exhibited an enhanced PA signal in hypoxic conditions. This study demonstrates the potential of hypoxia-responsive AuNPs as novel and sensitive diagnostic agents, which lays a firm foundation for precise cancer treatment in the future.

Biomimetic Anti-PD-1 Peptide-Loaded 2D FePSe3 Nanosheets for Efficient Photothermal and Enhanced Immune Therapy with Multimodal MR/PA/Thermal Imaging.

Metal phosphorous trichalcogenides (MPX3) are novel 2D nanomaterials that have recently been exploited as efficient photothermal-chemodynamic agents for cancer therapy. As a representative MPX3, FePSe3 has the potential to be developed as magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) agents due to the composition of Fe and the previously revealed PA signal. Here, a FePSe3-based theranostic agent, FePSe3@APP@CCM, loaded with anti-PD-1 peptide (APP) as the inner component and CT26 cancer cell membrane (CCM) as the outer shell is reported, which acts as a multifunctional agent for MR and PA imaging and photothermal and immunotherapy against cancer. FePSe3@APP@CCM induces highly efficient tumor ablation and suppresses tumor growth by photothermal therapy under near-infrared laser excitation, which further activates immune responses. Moreover, APP blocks the PD-1/PD-L1 pathway to activate cytotoxic T cells, causing strong anticancer immunity. The combined therapy significantly prolongs the lifespan of experimental mice. The multimodal imaging and synergistic therapeutic effects of PTT and its triggered immune responses and APP-related immunotherapy are clearly demonstrated by in vitro and in vivo experiments. This work demonstrates the potential of MPX3-based biomaterials as novel theranostic agents.

pH-Triggered Poly(ethylene glycol)-Poly(lactic acid/glycolic acid)/Croconaine Nanoparticles-Assisted Multiplexed Photoacoustic Imaging and Enhanced Photothermal Cancer Therapy.

The most advantageous and attractive property of photoacoustic imaging is its capability to visualize and differentiate multiple species according to their unique absorbance profiles simultaneously in a single mixture. We here report the pH-sensitive near-infrared (NIR) croconaine (Croc) dyes-loaded copolymeric PEG-PLGA nanoparticles (NPs) for in vivo multiplexed PA imaging and pH-responsive photothermal therapy (PTT) in an orthotopic xenograft model. PEG chains on the polymeric NPs shell were conjugated with iRGD in another set of NPs to realize efficient tumor targeting. The distribution and the intensity of two sets of iRGD-targeted and nontargeted NPs inside tumors are simultaneously imaged and monitored in vivo. Meanwhile, the utilization of iRGD-targeted PPC815 NPs as a pH-active photothermal agent with promising tumor-inhibition efficacy was demonstrated. As a result, this nanoplatform is capable of assisting multiwavelength unmixing of PA imaging as well as providing remarkable photothermal ablation for anticancer treatment.

Multifunctional Nanotheranostic Gold Nanocage/Selenium Core-Shell for PAI-Guided Chemo-Photothermal Synergistic Therapy in vivo.

INTRODUCTION: Cancer theragnosis involving cancer diagnosis and targeted therapy simultaneously in one integrated system would be a promising solution of cancer treatment. Herein, a convenient and practical cancer theragnosis agent was constructed by combining gold nanocages (AuNCs) covered with selenium and a chitosan (CS) shell (AuNCs/Se) to incorporate the anti-cancer drug doxorubicin (DOX) as a multifunctional targeting nanocomposite (AuNCs/DOX@Se-iRGD) for photoacoustic imaging (PAI)-guided chemo-photothermal synergistic therapy that contributes to enhanced anti-cancer efficacy. The novel design of AuNCs/DOX@Se-iRGD gives the nanocomposite two outstanding properties: (1) AuNCs, with excellent LSPR property in the NIR region, act as a contrast agent for enhanced PAI and photothermal therapy (PTT); (2) Se acts as an anti-cancer nanoagent and drug delivery cargo. METHODS: The photothermal performance of these nanocomposites was evaluated in different concentrations with laser powder densities. These nanocomposites were also incubated in pH 5.3, 6.5, 7.4 PBS and NIR laser to study their drug release ability. The cellular uptake was studied by measuring the Se and Au concentrations inside the cells using inductively coupled plasma-mass spectrometry (ICP-MS). Besides, in vitro and in vivo anti-tumor activity were carried out by cytotoxicity assay MTT and tumor model nude mice, respectively. As for imaging, the PA value and images of these nanocomposites accumulated in the tumor site were sequentially collected at specific time points for 48 h. RESULTS AND DISCUSSION: The prepared AuNCs/DOX@Se-iRGD showed excellent biocompatibility and physiological stability in different media. In vivo results indicated that the targeting nanocomposite presented the strongest contrast-enhanced PAI signals, which could provide contour and location information of tumor, 24 h after intravenous injection. Likewise, the combined treatment of chemo- and photothermal synergistic therapy significantly inhibited tumor growth when compared with the two treatments carried out separately and showed negligible acute toxicity to the major organs. CONCLUSION: This study demonstrates that AuNCs/DOX@Se-iRGD has great prospect to become a multifunctional anti-tumor nanosystem for PAI-guided chemo- and photothermal synergistic therapy.

Dual-Targeted Selenium Nanoparticles for Synergistic Photothermal Therapy and Chemotherapy of Tumors.

A combination of chemo- and photothermal therapy has emerged as a promising tactic for cancer therapy. However, the intricacy of accurate delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle. Hence, to assure that the chemotherapeutic drug and photothermal agent are synchronously delivered to a tumor area for their synergistic effect, dual-target (RC-12 and PG-6 peptides) functionalized selenium nanoparticles loaded with both doxorubicin (DOX) and indocyanine green (ICG) were designed and successfully synthesized. The as-synthesized nanoparticles exhibited good monodispersity, size stability, and consistent spectral characteristics compared with those of ICG or DOX alone. The nanoparticles underwent self-immolated cleavage under irradiation from a near-IR laser and released the loaded drug owing to sufficient hyperthermia. Moreover, the internalized nanoparticles triggered the overproduction of intracellular reactive oxygen species to induce cell apoptosis. Taken together, this study provides a sequentially triggered nanosystem to achieve precise drug delivery by chemo-photothermal combination.

Bioresponsive cancer-targeted polysaccharide nanosystem to inhibit angiogenesis.

With many desirable features, such as being more effective and having multiple effects, antiangiogenesis has become one of the promising cancer treatments. The aim of this study was to design and synthesize a new targeted bioresponsive nanosystem with antiangiogenesis properties. The mUPR@Ru(POP) nanosystem was constructed by the polymerization of Ulva lactuca polysaccharide and N-isopropyl acrylamide, decorated with methoxy polyethylene glycol and Arg-Gly-Asp peptide, and encapsulated with anticancer complex [Ru(phen)2p-MOPIP](PF6)2·2H2O. The nanosystem was both pH responsive and targeted. Therefore, the cellular uptake of the drug was greatly improved. Moreover, the mUPR@Ru(POP) had strong suppressive effects against vascular endothelial growth factor (VEGF)-induced angiogenesis through apoptosis. The mUPR@Ru(POP) significantly inhibited VEGF-induced human umbilical vein endothelial cell migration, invasion, and tube formation. These findings have presented new insights into the development of antiangiogenesis drugs.

Size changeable nanosystems for precise drug controlled release and efficient overcoming of cancer multidrug resistance.

Multidrug resistance is one of the main causes leading to failure of chemotherapy. Therefore, the rational design of targeting drug systems to reverse multidrug resistance is becoming an important strategy for cancer therapy. Herein, we present a novel copolymer-based nanoparticle that was size changeable and could realize the goal of precise drug controlled release under acidic conditions, and could overcome the multidrug resistance in breast cancer cells. This PCP/uPA nanosystem was formed through the crosslinking between chitosan (CS) and poly(N-isopropylacrylamide) (PNIPAM), followed by surface decoration with polyethylene glycol (mPEG) and a breast cancer targeting peptide uPA, which was then used to encapsulate metal complexes (RuPOP and Fe(PiP)3) to solve their bottleneck of low solubility and stability under physiological conditions. These multifunctional nanosystems (PCP-Ru/uPA and PCP-Fe/uPA) exhibited remarkable anticancer activity and could overcome the poor stability and low solubility of RuPOP and Fe(PiP)3. Noticeably, PCP-Ru/uPA reversed the multidrug resistance of drug-resistant MCF-7 (MCF-7R) human breast cancer cells by enhancing the cellular uptake of RuPOP by MCF-7R cells and inhibiting the expression of ABC family proteins. Furthermore, when PCP-Ru/uPA was at pH 5.3 with lysozyme, the release amount of RuPOP is the largest compared with pH at 5.3 or 7.4, and the release rate of RuPOP reached 75% at 48 h. In other words, the nanosystem with a pH-responsive effect swelled in an acidic environment and released free RuPOP in the lysosome of cancer cells efficiently, which triggered ROS up-regulation and induced apoptosis in MCF-7R cells. Taken together, this study presents a novel size changeable nanosystem for precise drug controlled release and efficient overcoming of cancer multidrug resistance.