Tandem Photon Avalanches for Various Nanoscale Emitters with Optical Nonlinearity up to 41st-Order through Interfacial Energy Transfer.

Photon avalanche has received continuous attention owing to its superior nonlinear dynamics and promising advanced applications. However, its impact is limited due to the intrinsic energy levels as well as the harsh requirements for the composites and sizes of doped materials. Here, with a universal mechanism named tandem photon avalanche (TPA), giant optical nonlinear response up to 41st-order in erbium ions, one of the most important lanthanide emitters, has been achieved on the nanoscale through interfacial energy transfer process. After capturing energy directly from the avalanched energy state 3 H4 of Tm3+ (800-nm emission), erbium ions also exhibit bright green and red PA emissions with intensities comparable to that of Tm3+ at a low excitation threshold (7.1 kWcm-2 ). Using the same strategy, effective PA looping cycles are successfully activated in Ce3+ and Ho3+ . Additionally, Yb3+ -mediated networks are constructed to further propagate PA effects to lowly-doped Tm3+ , enabling 475-nm PA emission. The newly proposed TPA strategy provides a facile route for generating photon avalanche not only from erbium ions but also from various emitters in multilayered core-shell nanoparticles.

Cu2+ coordination-induced in situ photo-to-heat on catalytic sites to hydrolyze ß-lactam antibiotics pollutants in waters.

For degradation of ß-lactam antibiotics pollution in waters, the strained ß-lactam ring is the most toxic and resistant moiety to biodegrade and redox-chemically treat among their functional groups. Hydrolytically opening ß-lactam ring with Lewis acid catalysts has long been recognized as a shortcut, but at room temperature, such hydrolysis is too slow to be deployed. Here, we found when Cu2+ was immobilized on imine-linked COF (covalent organic framework) (Cu2+/Py-Bpy-COF, Cu2+ load is 1.43 wt%), as-prepared composite can utilize the light irradiation (wavelength range simulated sunlight) to in situ heat anchored Cu2+ Lewis acid sites through an excellent photothermal conversion to open the ß-lactam ring followed by a desired full-decarboxylation of hydrolysates. Under 1 W/cm2 simulated sunlight, Cu2+/Py-Bpy-COF powders placed in a microfiltration membrane rapidly cause a temperature rising even to ~211.7 °C in 1 min. It can effectively hydrolyze common ß-lactam antibiotics in waters and even antibiotics concentration is as high as 1 mM and it takes less than 10 min. Such photo-heating hydrolysis rate is ~24 times as high as under dark and ~2 times as high as Cu2+ homogenous catalysis. Our strategy significantly decreases the interference from generally coexisting common organics in waters and potential toxicity concerns of residual carboxyl groups in hydrolysates and opens up an accessible way for the settlement of ß-lactam antibiotics pollutants by the only energy source available, the sunlight.

Nanomaterials-based precision sonodynamic therapy enhancing immune checkpoint blockade: A promising strategy targeting solid tumor.

Burgeoning is an evolution from conventional photodynamic therapy (PDT). Thus, sonodynamic therapy (SDT) regulated by nanoparticles (NPs) possesses multiple advantages, including stronger penetration ability, better biological safety, and not reactive oxygen species (ROS)-dependent tumor-killing effect. However, the limitation to tumor inhibition instead of shrinkage and the incapability of eliminating metastatic tumors hinder the clinical potential for SDT. Fortunately, immune checkpoint blockade (ICB) can revive immunological function and induce a long-term immune memory against tumor rechallenges. Hence, synergizing NPs-based SDT with ICB can provide a promising therapeutic outcome for solid tumors. Herein, we briefly reviewed the progress in NPs-based SDT and ICB therapy. We highlighted the synergistic anti-tumor mechanisms and summarized the representative preclinical trials on SDT-assisted immunotherapy. Compared to other reviews, we provided comprehensive and unique perspectives on the innovative sonosensitizers in each trial. Moreover, we also discussed the current challenges and future corresponding solutions.

A Soft Robot Driven by a Spring-Rolling Dielectric Elastomer Actuator with Two Bristles.

Confined space searches such as pipeline inspections are widely demanded in various scenarios, where lightweight soft robots with inherent compliance to adapt to unstructured environments exhibit good potential. We proposed a tubular soft robot with a simple structure of a spring-rolled dielectric elastomer (SRDE) and compliant passive bristles. Due to the compliance of the bristles, the proposed robots can work in pipelines with inner diameters both larger and smaller than the one of the bristles. Firstly, the nonlinear dynamic behaviors of the SRDE were investigated experimentally. Then, we fabricated the proposed robot with a bristle diameter of 19 mm and then studied its performance in pipelines on the ground with inner diameters of 18 mm and 20 mm. When the pipeline's inner diameter was less than the outer diameter of the bristles, the bristles remained in the state of bending and the robot locomotion is mainly due to anisotropic friction (1.88 and 0.88 body lengths per second horizontally and vertically, respectively, in inner diameter of 18 mm and 0.06 body length per second in that of 16 mm). In the case of the pipeline with the larger inner diameter, the bristles were not fully constrained, and a small bending moment applied on the lower bristle legs contributed to the robot's locomotion, leading to a high velocity (2.78 body lengths per second in 20 mm diameter acrylic pipe). In addition, the robot can work in varying geometries, such as curving pipes (curve radius ranges from 0.11 m to 0.31 m) at around two body lengths per second horizontally and on the ground at 3.52 body lengths per second, showing promise for pipeline or narrow space inspections.

Leber's Hereditary Optic Neuropathy with Mitochondrial DNA Mutation G11778A: A Systematic Literature Review and Meta-Analysis.

Background: LHON is a progressive disease with early disease onset and male predominance, usually causing devastating visual loss to patients. These systematic review and meta-analysis are aimed at summarizing epidemiology, disease onset and progression, visual recovery, risk factors, and treatment options of Leber's hereditary optic neuropathy (LHON) with mitochondrial DNA mutation G11778A from current evidence. Methods: The PubMed database was examined from its inception date to November 2021. Data from included studies were pooled with either a fixed-effects model or a random-effects model, depending on the results of heterogeneity tests. Sensitivity analysis was conducted to test the robustness of results. Results: A total of 41 articles were included in the systematic review for qualitative analysis, and 34 articles were included for quantitative meta-analysis. The pooled estimate of proportion of G11778A mutation among the three primary mutations of mitochondrial DNA (G11778A, G3460A, and T14484C) for LHON was 73% (95% CI: 67% and 79%), and the LHON patients with G11778A mutation included the pooled male ratio estimate of 77% (76% and 79%), the pooled age estimate of 35.3 years (33.2 years and 37.3 years), the pooled onset age estimate of 22.1 years (19.7 years and 24.6 years), the pooled visual acuity estimate of 1.4 LogMAR (1.2 LogMAR and 1.6 LogMAR), and the pooled estimate of spontaneous visual recovery rate (in either 1 eye) of 20% (15% and 27%). Conclusions: The G11778A mutation is a prevalent mitochondrial DNA mutation accounting for over half of LHON cases with three primary mutations. Spontaneous visual recovery is rare, and no effective treatment is currently available.

A Bimetallic Metal-Organic-Framework-Based Biomimetic Nanoplatform Enhances Anti-Leukemia Immunity via Synchronizing DNA Demethylation and RNA Hypermethylation.

Epigenetic-alterations-mediated antigenicity reducing in leukemic blasts (LBs) is one of the critical mechanisms of immune escape and resistance to T-cell-based immunotherapy. Herein, a bimetallic metal-organic framework (MOF)-based biomimetic nanoplatform (termed as AFMMB) that consists of a DNA hypomethylating agent, a leukemia stem cell (LSC) membrane, and pro-autophagic peptide is fabricated. These AFMMB particles selectively target not only LBs but also LSCs due to the homing effect and immune compatibility of the LSC membrane, and induce autophagy by binding to the Golgi-apparatus-associated protein. The autophagy-triggered dissolution of AFMMB releases active components, resulting in the restoration of the stimulator of interferon genes pathway by inhibiting DNA methylation, upregulation of major histocompatibility complex class-I molecules, and induction of RNA-methylation-mediated decay of programmed cell death protein ligand transcripts. These dual epigenetic changes eventually enhance T-cell-mediated immune response due to increased antigenicity of leukemic cells. AFMMB also can suppress growth and metastases of solid tumor, which was suggestive of a pan-cancer effect. These findings demonstrate that AFMMB may serve as a promising new nanoplatform for dual epigenetic therapy against cancer and warrants clinical validation.

Efficacy and safety of pyrotinib-containing regimen in the patients with HER2-positive metastatic breast cancer: A multicenter real-world study.

BACKGROUND: Pyrotinib, a novel irreversible epidermal growth factor receptor 2 (EGFR)/HER2 dual tyrosine kinase inhibitor, has shown promising antitumor efficacy with tolerable toxicity in HER2-positive metastatic breast cancer (MBC) in several clinical trials. However, the clinical trials do not usually well reflect the patients in real clinical settings. Despite several small-sample studies in real world, the data on pyrotinib as first-line and third-or-later-line treatment and the efficacy comparison of pyrotinib combined with different regimens are still lacking. Therefore, this study aimed to investigate the efficacy and safety of pyrotinib for the HER2-positive MBC in real world to replenish more comprehensive data. METHODS: A total of 172 HER2-positive MBC patients treated with pyrotinib-based therapy were recruited from multiple centers in nonclinical trial settings from September 2017 to June 2020. RESULTS: The median progression-free survival (mPFS) of 172 patients was 8.83 months. The patients, receiving first-line pyrotinib treatment, had the longest mPFS (20.93 months) compared with those receiving second-line (8.67 months, p = 0.0339) and third-or-later-line (7.13 months, p = 0.0075) treatments, respectively. Prior treatment with lapatinib (p = 0.012) and site of metastasis (visceral vs. nonvisceral) (p = 0.033) were the independent prognostic factors for PFS. The prior treatment with lapatinib compared with lapatinib-native treatment (5.96 vs. 10.97 months, p = 0.0036) and those with visceral metastasis compared with nonvisceral metastasis (8.40 vs. 23.70 months, p = 0.0138) had worse mPFS. Among 146 patients evaluated for efficacy, 2.1%, 58.9%, and 32.9% showed complete response, partial response, and stable disease, respectively. Adverse events occurred in 92.4% of the patients with 33.3% Grade 3 and higher adverse events and diarrhea (57.0%), anemia (44.8%), and leukopenia (40.7%) as the most frequent ones. CONCLUSIONS: Pyrotinib-containing regimen could effectively treat HER2-positive MBC with acceptable toxicity, including the patients who progressed after lapatinib treatment and with brain metastasis.

Many Roads Lead to Rome: Differential Learning Processes for the Same Perceptual Improvement.

Repeatedly exercising a perceptual ability usually leads to improvement, yet it is unclear whether the mechanisms supporting the same perceptual learning could be flexibly adjusted according to the training settings. Here, we trained adult observers in an orientation-discrimination task at either a single (focused) retinal location or multiple (distributed) retinal locations. We examined the observers' discriminability (N = 52) and bias (N = 20) in orientation perception at the trained and untrained locations. The focused and distributed training enhanced orientation discriminability by the same amount and induced a bias in perceived orientation at the trained locations. Nevertheless, the distributed training promoted location generalization of both practice effects, whereas the focused training resulted in specificity. The two training tactics also differed in long-term retention of the training effects. Our results suggest that, depending on the training settings of the same task, the same discrimination learning could differentially engage location-specific and location-invariant representations of the learned stimulus feature.

Facile Approach to Fabricate Oriented Porous PDMS Composites for Movements Monitoring and Identifying Motion Patterns.

The facile and rapid fabrication of oriented porous polymers is crucial for flexible pressure sensors. Herein, a pressure sensor is developed based on oriented porous polydimethylsiloxane (PDMS) composites for detecting human motion and identifying joint motion patterns. The oriented porous PDMS composite is first constructed through thiol-ene click chemistry and directional freezing within only 30 min, then fabricated by interfacial in situ polymerization of dopamine and pyrrole to generate robust interfaces. As a result, the as-prepared oriented porous PDMS composite is assembled into a pressure sensor that shows potential applications in pressure and human motion detection. Interestingly, a sensor assembled by orthogonally stacking the PDMS composites can be used for joint motion pattern recognition with potential monitoring of football motion due to their directional structures. This facile strategy coupled with the oriented porous structure is expected to help design advanced wearable electronic devices.

Glycyrrhetinic acid nanoparticles combined with ferrotherapy for improved cancer immunotherapy.

Programmed cell death protein 1 (PD-1)/Programmed Cell Death Ligand 1 (PD-L1) blockade immunotherapy has emerged as a promising strategy to treat both solid and hematological malignancies. Despite the considerable therapeutic effects obtained in pre-clinical and clinical studies, PD-1/PD-L1 blockade therapy is still limited by the low benefit rates and a large number of patients still do not respond to this treatment. In this study, we developed a highly efficient and cancer-specific immunogenic cell death nanoinducer for effective tumor immunotherapy. A leukocyte membrane coated poly (lactic-co-glycolic acid) encapsulating glycyrrhetinic acid (GCMNPs) was developed to enhance targeting, tumor-homing capacity, and reduce toxicity in vivo. GCMNPs could induce ferroptosis in acute myeloid leukemia and colorectal cancer cells by downregulating glutathione-dependent peroxidases 4, leading to increased lipid peroxidation levels. Moreover, GCMNPs and ferumoxytol could synergistically enhance Fe-dependent cytotoxicity through the Fenton reaction. Finally, in vivo studies showed that GCMNPs synergized with ferumoxytol and anti-PD-L1 synergistically improve T-cell immune response against leukemia and colorectal tumor. This study anticipated that the combination of glycyrrhetinic acid-based nanomaterials and ferrotherapy would provide further insights into anti-cancer immune response to PD-1/PD-L1 blockade for both solid and hematological malignancies. STATEMENT OF SIGNIFICANCE: Despite the considerable therapeutic effects obtained in pre-clinical and clinical studies, PD-1/PD-L1 blockade therapy is still limited by the low benefit rates and a large number of patients still do not respond to this treatment. We designed a glycyrrhetinic acid-based nanoplatform as a new ICD inducer (GCMNPs), with high cancer cell specificity and reduced toxicity to AML and CRC. GCMNPs cooperates with ferumoxytol to promote a Fenton reaction and induce ferroptosis. Moreover, the combination of GCMNPs and ferumoxytol enhanced the blockage of PD-1/PD-L1 to activate T cells, subsequently generating a systemic immune response in CRC and AML mouse models. This pre-clinical findings provide the proof-of-concept of combination of glycyrrhetinic acid-based nanomaterials and ferrotherapy as an "ICD nano-inducer" and immunotherapeutic agent for treating cancer.

Glutathione-Bioimprinted Nanoparticles Targeting of N6-methyladenosine FTO Demethylase as a Strategy against Leukemic Stem Cells.

The N6-methyladenosine (m6 A) demethylase FTO plays an oncogenic role in acute myeloid leukemia (AML). Despite the promising recent progress for developing some small-molecule FTO inhibitors, the clinical potential remains limited due to mild biological function, toxic side effects and low sensitivity and/or specificity to leukemic stem cells (LSCs). Herein, FTO inhibitor-loaded GSH-bioimprinted nanocomposites (GNPIPP12MA) are developed that achieves targeting of the FTO/m6 A pathway synergized GSH depletion for enhancing anti-leukemogenesis. GNPIPP12MA can selectively target leukemia blasts, especially LSCs, and induce ferroptosis by disrupting intracellular redox status. In addition, GNPIPP12MA increases global m6 A RNA modification and decreases the transcript levels in LSCs. GNPIPP12MA augments the efficacy of the PD-L1 blockade by increasing the infiltration of cytotoxic T cells for enhanced anti-leukemia immunity. This study offers insights for a GSH-bioimprinted nanoplatform targeting m6 A RNA methylation as a synergistic treatment strategy against cancer stem cells that may translate to clinical applications.

Molten Salt Shielded Synthesis of Monodisperse Layered CaZnOS-Based Semiconductors for Piezophotonic and X-Ray Detection Applications.

CaZnOS-based semiconductors are the only series of material system discovered that can simultaneously realize a large number of dopant elements to directly fulfill the highly efficient full-spectrum functionality from ultraviolet to near-infrared under the same force/pressure. Nevertheless, owing to the high agglomeration of the high temperature solid phase manufacturing process, which is unable to control the crystal morphology, the application progress is limited. Here, the authors report first that CaZnOS-based fine monodisperse semiconductor crystals with various doping ions are successfully synthesized by a molten salt shielded method in an air environment. This method does not require inert gas ventilation, and therefore can greatly reduce the synthesis cost and more importantly improve the fine control of the crystal morphology, along with the crystals' dispersibility and stability. These doped semiconductors can not only realize different colors of mechanical-to-optical energy conversion, but also can achieve multicolor luminescence under low-dose X-ray irradiation, moreover their intensities are comparable to the commercial NaI:Tl. They can pave the way to the new fields of advanced optoelectronic applications, such as piezophotonic systems, mechanical energy conversion and harvesting devices, intelligent sensors, and artificial skin as well as X-ray applications.

Gold Nanorods Exhibit Intrinsic Therapeutic Activity via Controlling N6-Methyladenosine-Based Epitranscriptomics in Acute Myeloid Leukemia.

Reprograming the N6-methyladenosine (m6A) landscape is a promising therapeutic strategy against recalcitrant leukemia. In this study, we synthesized gold nanorods (GNRs) of different aspect ratios using a binary surfactant mixture of hexadecyltrimethylammonium bromide and sodium oleate. Following surface functionalization with chitosan and a 12-mer peptide, GNRa-CSP12 measuring 130 × 21 nm2 was selectively taken up by leukemia cells via targeted endocytosis. Low doses of GNRa-CSP12 inhibited the growth of leukemia cells by disrupting the redox balance and inducing ferroptosis. Mechanistically, GNRa-CSP12 abrogated endogenous Fe2+-dependent m6A demethylase activity, which led to global m6A hypomethylation and post-transcriptional regulation of downstream genes that are involved in glycolysis, hypoxia, and immune checkpoint pathways. In addition, combination treatment with GNRa-CSP12 and tyrosine kinases inhibitors (TKIs) synergistically obviated the m6A-mediated TKI resistance phenotype. Finally, GNRa-CSP12 as a potential immunotherapeutic agent could enhance immunotherapy outcome in leukemia. Our preclinical findings provide the proof-of-concept for targeting m6A-methylation-based epitranscriptomics using nanoparticle as an "epigenetic drug" for cancer therapy.

Tumor-Associated-Macrophage-Membrane-Coated Nanoparticles for Improved Photodynamic Immunotherapy.

Cell-membrane-coated nanoparticles have emerged as a promising antitumor therapeutic strategy. However, the immunologic mechanism remains elusive, and there are still crucial issues to be addressed including tumor-homing capacity, immune incompatibility, and immunogenicity. Here, we reported a tumor-associated macrophage membrane (TAMM) derived from the primary tumor with unique antigen-homing affinity capacity and immune compatibility. TAMM could deplete the CSF1 secreted by tumor cells in the tumor microenvironment (TME), blocking the interaction between TAM and cancer cells. Especially, after coating TAMM to upconversion nanoparticle with conjugated photosensitizer (NPR@TAMM), NPR@TAMM-mediated photodynamic immunotherapy switched the activation of macrophages from an immunosuppressive M2-like phenotype to a more inflammatory M1-like state, induced immunogenic cell death, and consequently enhanced the antitumor immunity efficiency via activation of antigen-presenting cells to stimulate the production of tumor-specific effector T cells in metastatic tumors. This TAM-membrane-based photodynamic immunotherapy approach offers a new strategy for personalized tumor therapy.

Saikosaponin D exhibits anti-leukemic activity by targeting FTO/m6A signaling.

Purpose: The implementation of targeted therapies for acute myeloid leukemia (AML) has been challenging. Fat mass and obesity associated protein (FTO), an mRNA N6-methyladenosine (m6A) demethylase, functions as an oncogene that promotes leukemic oncogene-mediated cell transformation and leukemogenesis. Here, we investigated the role of Saikosaponin-d (SsD) in broad anti-proliferation effects in AML and evaluated the m6A demethylation activity by targeting FTO of SsD. Methods: It was examined whether and how SsD regulates FTO/m6A signaling in AML. The pharmacologic activities and mechanisms of actions of SsD in vitro, in mice, primary patient cells, and tyrosine kinase inhibitors-resistant cells were determined. Results: SsD showed a broadly-suppressed AML cell proliferation and promoted apoptosis and cell-cycle arrest both in vitro and in vivo. Mechanistically, SsD directly targeted FTO, thereby increasing global m6A RNA methylation, which in turn decreased the stability of downstream gene transcripts, leading to the suppression of relevant pathways. Importantly, SsD also overcame FTO/m6A-mediated leukemia resistance to tyrosine kinase inhibitors. Conclusion: Our findings demonstrated that FTO-dependent m6A RNA methylation mediated the anti-leukemic actions of SsD, thereby opening a window to develop SsD as an epitranscriptome-base drug for leukemia therapy.

Characterisation of thickness changes in the peripapillary retinal nerve fibre layer in patients with Leber's hereditary optic neuropathy.

BACKGROUND: Limited studies have identified the changes in peripapillary retinal nerve fibre layer (pRNFL) thickness in patients with chronic Leber's hereditary optic neuropathy (LHON) at different stages of the disease. We aimed to characterise the pRNFL thickness changes in patients with LHON having m.11778G>A (MT-ND4) mutation. METHODS: This retrospective cross-sectional study included 221 eyes from patients with LHON (n=145)-classified into seven groups according to disease duration-and 52 eyes from healthy controls (n=26). All subjects underwent pRNFL examinations. pRNFL thickness of the superior, nasal and inferior, and temporal quadrants, and the 360° average were measured. RESULTS: Within 3 months of onset, the temporal pRNFL thickness decreased significantly, whereas the remaining quadrants and the average pRNFL thickness initially increased. The temporal quadrant (p<0.01) and average pRNFL thickness (p=0.02) significantly decreased at 3-6 months. Excluding that in the nasal quadrant (p=0.93), pRNFL thickness significantly decreased in all other quadrants at 6-9 months. At 9-12 months, the average and individual quadrant pRNFL thicknesses continued to decrease. Compared with 12-24 months, the pRNFL thickness was thinner at 24-60 months and >60 months. CONCLUSIONS: The papillomacular bundle was affected first and preferentially in LHON. pRNFL thickness initially increased and then decreased, corresponding to the retinal ganglion cell swelling and apoptosis. pRNFL thinning first occurred in the temporal quadrant, followed by the inferior and superior quadrants, and finally, the nasal quadrant. pRNFL continued to thin slowly in some quadrants even after 60 months.

Fe3O4 and iminodiacetic acid modified peanut husk as a novel adsorbent for the uptake of Cu (II) and Pb (II) in aqueous solution: Characterization, equilibrium and kinetic study.

The presence of higher concentrations of heavy metals in water affects its quality with a concomitant adverse effect on its users thus their removal is paramount. A novel adsorbent, PN-Fe3O4-IDA derived from the chemical modification of peanut husk (a low-cost agricultural biomass produced in significant quantities globally) using magnetic nanoparticles (Fe3O4) and iminodiacetic acid was utilized for the remediation of heavy metals in aqueous solution. Analytical techniques vis-à-vis the Fourier-Transform Infrared, Scanning Electron Microscope, Brunauer-Emmett-Teller, X-ray photoelectron spectroscopy and X-ray Diffraction were applied for the characterization of PN-Fe3O4-IDA. Results from the characterization studies showed that PN-Fe3O4-IDA possessed a mesoporous structure, a heterogeneous surface and functional groups such as carboxylic acid and a tertiary nitrogen atom which enhanced its adsorption capacities as well as magnetic properties which ensured its easy removal from the solution using a magnet. The maximum uptake of Pb and Cu onto PN-Fe3O4-IDA was 0.36 and 0.75 mmol g-1 (at 318 K) respectively with the chemisorption process being the major reaction pathway for the processes. The synthesized adsorbent exhibits significant adsorption capacity for the selected pollutants as well as some unique features which promotes its use as an adsorbent for wastewater remediation processes.

Fluorescent nanorods based on 9,10-distyrylanthracene (DSA) derivatives for efficient and long-term bioimaging.

Fluorescent nanoparticles based on 9,10-distyrylanthracene (DSA) derivatives (4,4'-((1E,1'E)-anthracene-9,10-diylbis(ethene-2,1-diyl))bis(N,N-dimethylaniline) (NDSA) and 4,4'-((1E,1'E)-anthracene-9,10-diylbis(ethene-2,1-diyl))dibenzonitrile (CNDSA)) were prepared using an ultrasound aided nanoprecipitation method. The morphologies of the fluorescent nanoparticles could be controlled by adjusting the external ultrasonication time. NDSA or CNDSA could form spherical nanodots (NDSA NDs, CNDSA NDs) in a THF-H2O mixture with an 80% or 70% water fraction when the ultrasonication time was 30 s. When the ultrasonication time was prolonged to 10 min, NDSA and CNDSA could assemble into nanorods (NDSA NRs, CNDSA NRs). Meanwhile, the sizes of NDSA NRs and CNDSA NRs could be controlled by adjusting the water content in the mixture. As the water fraction was increased from 60% to 80%, the sizes of NDSA and CNDSA nanorods or nanodots reduced from 238.4 nm to 140.3 nm, and 482 nm to 198.4 nm, respectively. When the water fraction was up to 90%, irregular morphologies of NDSA and CNDSA could be observed. The nanoparticles exhibited intense fluorescence emission, good anti-photobleaching properties, as well as excellent stability and biocompatibility. In vitro cell imaging experiments indicated that the nanorods prepared by this simple method had the potential to be used for efficient and noninvasive long-term bioimaging.

Bortezomib-Encapsulated CuS/Carbon Dot Nanocomposites for Enhanced Photothermal Therapy via Stabilization of Polyubiquitinated Substrates in the Proteasomal Degradation Pathway.

Photothermal therapy (PTT) is an emerging therapeutic strategy in the treatment of cancer; however, a critical challenge remains in the rational design of synergistic nanoparticles as a potential photothermal transduction agent that can effectively enhance the therapeutic outcome of PTT for tumor ablation. Herein, we rationally designed, developed, and characterized hollow-structured CuS nanoparticles composited with carbon dots (CuSCDs), which demonstrated excellent photothermal conversion efficiency under a 808 nm laser irradiation with enhanced biocompatibility and reduced toxicity. Following coating with a macrophage membrane hybridized with T7 peptide on the surface of the proteasome inhibitor loaded CuSCD, CuSCDB@MMT7 exhibited targeted specificity to cancer cells with the characteristics of immunity escaping and enhanced transferrin receptor-mediated endocytosis. Predominantly, CuSCDB@MMT7-triggered PTT exhibited the accumulation of the polyubiquitinated tumor suppressor protein that is heat stabilized under NIR induced hyperthermia, facilitating augmented tumor cell apoptosis and the attenuated metastasis. This study provides a proof-of-concept for the proteasome inhibitor-loaded CuS/carbon dot nanocomposite-PTT strategy and highlights a promising therapeutic strategy for realizing enhanced therapeutic outcomes for effective clinical cancer therapy.