A Highly Sensitive D-Shaped PCF-SPR Sensor for Refractive Index and Temperature Detection.

A novel highly sensitive D-shaped photonic crystal fiber-based surface plasmon resonance (PCF-SPR) sensor for dual parameters of refractive index and temperature detecting is proposed. A PCF cladding polishing provides a D-shape design with a gold (Au) film coating for refractive index (RI) sensing (Core 1) and a composite film of silver (Ag) and polydimethylsiloxane (PDMS) for temperature sensing (Core 2). Comsol Multiphysics 5.5 is used to design and simulate the proposed sensor by the finite element method (FEM). The proposed sensor numerically provides results with maximum wavelength sensitivities (WSs) of 51,200 and 56,700 nm/RIU for Core 1 and 2 as RI sensing while amplitude sensitivities are -98.9 and -147.6 RIU-1 with spectral resolution of 1.95 × 10-6 and 1.76 × 10-6 RIU, respectively. Notably, wavelength sensitivity of 17.4 nm/°C is obtained between -20 and -10 °C with resolution of 5.74 × 10-3 °C for Core 2 as temperature sensing. This sensor can efficiently work in the analyte and temperature ranges of 1.33-1.43 RI and -20-100 °C. Due to its high sensitivity and wide detection ranges, both in T and RI sensing, it is a promising candidate for a variety of applications, including chemical, medical, and environmental detection.

A novel borate phosphor Lu5Ba6B9O27:Ce3+ codoped with Sr2+/Tb3+ for NUV-white light emitting diode application.

At present, there are still challenges in developing highly efficient and thermally stable phosphors for ultraviolet/near ultraviolet-white light emitting diodes (UV/NUV-WLEDs). Herein, we use traditional high-temperature solid-state reactions to prepare blue-emitting phosphors Lu5-xBa6B9O27:xCe3+ (0.1% ≤ x ≤ 3.0%) and Lu4.975Ba6-ySryB9O27:0.5%Ce3+ (0% ≤ y ≤ 20%), and green-emitting phosphors Lu4.975-zBa6B9O27:0.5%Ce3+,zTb3+ (0% ≤ z ≤ 16%), abbreviated as LBB:xCe3+, LBB:0.5%Ce3+,ySr2+ and LBB:0.5%Ce3+,zTb3+, respectively. Upon 340 nm excitation, LBB:Ce3+ exhibits an asymmetric blue emission ranging from 360 nm to 480 nm. Furthermore, the emission intensity of LBB:0.5%Ce3+ increased 4.8-fold without a spectral shift through the partial substitution of Sr2+ for Ba2+. Through constructing the Ce3+ → Tb3+ energy transfer in the LBB structure, the temperature-dependent integral emission intensity at 483 K improved from only 25% to 68% of the intensity at 303 K due to the existence of fast energy transfer from Ce3+ to Tb3+. The related results indicate that LBB:xCe3+, LBB:0.5%Ce3+,ySr2+ and LBB:0.5%Ce3+,zTb3+ phosphors can be used for UV/NUV-WLEDs.

Enhanced removal of PPCPs and antibiotic resistance genes in saline wastewater using a bioelectrochemical-constructed wetland system.

Pharmaceuticals and personal care products (PPCPs) are insufficiently degraded in saline wastewater treatment processes and are found at high concentrations and detection frequencies in aquatic environments. In this study, the wetland plant Thalia dealbata was selected using a screening plant experiment to ensure good salt tolerance and high efficiency in removing PPCPs. An electric integrated vertical-flow constructed wetland (E-VFCW) was developed to improve the removal of PPCPs and reduce the abundance of antibiotic resistance genes (ARGs). The removal efficiency of ofloxacin, enrofloxacin, and diclofenac in the system with anaerobic cathodic and aerobic anodic chambers is higher than that of the control system (41.84 ± 2.88%, 47.29 ± 3.01%, 53.29 ± 2.54%) by approximately 20.31%, 16.04%, and 35.25%. The removal efficiency of ibuprofen in the system with the aerobic anodic and anaerobic cathodic chamber was 28.51% higher than that of the control system (72.41 ± 3.06%) and promotes the reduction of ARGs. Electrical stimulation can increase the activity of plant enzymes, increasing their adaptability to stress caused by PPCPs, and PPCPs are transferred to plants. Species related to PPCPs biodegradation (Geobacter, Lactococcus, Hydrogenophaga, and Nitrospira) were enriched in the anodic and cathodic chambers of the system. This study provides an essential reference for the removal of PPCPs in saline-constructed wetlands.

Performance of pharmaceutical products removal in a bioelectrochemical system at low temperatures and changes in microbial communities and antibiotic resistance genes.

Biological methods do not effectively remove pharmaceutical products (PPs) and antibiotic resistance genes (ARGs) from wastewater at low temperatures, leading to environmental pollution. Therefore, anaerobic-aerobic-coupled upflow bioelectrochemical reactors (AO-UBERs) were designed to improve the removal of PPs at low temperatures (10 ± 2 °C). The result shows that diclofenac (DIC) and ibuprofen (IBU) removals in the system with aerobic anodic and anaerobic cathodic chambers were 91.7% and 94.7%, higher than that in the control system (12.2 ± 1.5%, 36.5 ± 5.9%), and aerobic zone favors DIC and IBU removal; fluoroquinolone antibiotics (FQs) removals in the system with aerobic cathodic and anaerobic anodic chambers were 17.5-22.4% higher than that in the control system (9.1-22.4%), and anaerobic zone favors FQs removal. Analysis of microbial community structure and ARGs showed that different electrotrophic microbes (Flavobacterium, Acinetobacter, and Delftia) with cold-resistant ability to degrade PPs were enriched in different electrode combinations, and the aerobic cathodic chambers could remove certain ARGs. These results showed that AO-UBERs under intermittent electrical stimulation mode are an alternative method for the effective removal of PPs and ARGs at low temperatures.

High-order LP modes based Sagnac interference for temperature sensing with an enhanced optical Vernier effect.

In this paper, high-order LP modes based Sagnac interference for temperature sensing are proposed and investigated theoretically. Based on the specific high-order LP modes excited through the mode selective couplers (MSCs), we design a stress-induced Panda-type few-mode fiber (FMF) supporting 4 LP modes and construct a Sagnac interferometer to achieve a highly sensitive temperature sensor. The performances of different LP modes (LP01, LP11, LP21, and LP02) are explored under a single Sagnac interferometer and paralleled Sagnac interferometers, respectively. LP21 mode has the highest temperature sensitivity. Compared with fundamental mode (LP01), the temperature sensitivity based on LP21 mode improved by 18.2% at least. In addition, a way to achieve the enhanced optical Vernier effect is proposed. It should be noted that two Sagnac loops are located in two temperature boxes of opposite variation trends, respectively. Both two Sagnac interferometers act as the sensing element, which is different from the traditional optical Vernier effect. The temperature sensitivity of novel enhanced optical Vernier effect is magnified by 8 times, which is larger than 5 times the traditional Vernier effect. The novel approach avoids measurement errors and improves the stability of the sensing system. The focus of this research is on high-order mode interference, which has important guiding significance for the development of highly sensitive Sagnac sensors.

Structure-Based Virtual Screening Identifying Novel FOXM1 Inhibitors as the Lead Compounds for Glioblastoma.

BACKGROUND: Glioblastoma multiforme (GBM) is a highly heterogeneous brain tumor with limited treatment options and a poor prognosis. Cancer stem cells (CSCs) have emerged as a critical factor in GBM resistance and management, contributing to tumor growth, heterogeneity, and immunosuppression. The transcription factor FOXM1 has been identified as a key player in the progression, spread, and therapy resistance of various cancers, including GBM. OBJECTIVE: In this research, the objective was to perform structure-based in silico screening with the aim of identifying natural compounds proficient in targeting the DNA-binding domain (DBD) of the FOXM1 protein. METHODS: In this study, in silico tools were employed for screening a hundred naturally occurring compounds capable of targeting the FOXM1 protein. Through molecular docking analysis and pharmacokinetic profiling, five compounds were found to be promising candidates for extensive interaction with the FOXM1 protein. Further, these compounds were validated for the stability of the FOXM1-natural compound complex using molecular dynamics (MD) simulations. RESULTS: Four compounds, such as Withaferin A, Bryophyllin A, Silybin B, Sanguinarine and Troglitazone (control compound), emerged as promising candidates with substantial interactions with FOXM1, suggesting their potential as a protein inhibitor based on molecular docking investigations. After MD simulation analysis, the FOXM1- Bryophyllin A complex was found to maintain the highest stability, and the other three ligands had moderate but comparable binding affinities over a period of 100 ns. CONCLUSION: This study provides valuable insights into four promising FOXM1 inhibitors that have the ability to induce senescence in GBM stem cells. These findings contribute to the development of structure-based designing strategies for FOXM1 inhibitors and innovative therapeutic approaches for the treatment of Glioblastoma.

Potential toxicity of graphene (oxide) quantum dots via directly covering the active site of anterior gradient homolog 2 protein.

Graphene quantum dots (GQDs) have attracted significant attention in biomedicine, while extensive investigations have revealed a reverse regarding the potential biotoxicity of GQDs. In order to supplementing the understanding of the toxicity profile of GQDs, this study employs a molecular dynamics (MD) simulation approach to systematically investigate the potential toxicity of both GQDs and Graphene Oxide Quantum Dots (GOQDs) on the Anterior Gradient Homolog 2 (AGR2) protein, a key protein capable of protecting the intestine. We construct two typical simulation systems, in which an AGR2 protein is encircled by either GQDs or GOQDs. The MD results demonstrate that both GQDs and GOQDs can directly make contact with and even cover the active site (specifically, the Cys81 amino acid) of the AGR2 protein. This suggests that GQDs and GOQDs have the capability to inhibit or interfere with the normal biological interaction of the AGR2 active site with its target protein. Thus, GQDs and GOQDs exhibit potential detrimental effects on the AGR2 protein. Detailed analyses reveal that GQDs adhere to the Cys81 residue due to van der Waals (vdW) interaction forces, whereas GOQDs attach to the Cys81 residue through a combination of vdW (primary) and Coulomb (secondary) interactions. Furthermore, GQDs aggregation typically adsorb onto the AGR2 active site, while GOQDs adsorb to the active site of AGR2 one by one. Consequently, these findings shed new light on the potential adverse impact of GQDs and GOQDs on the AGR2 protein via directly covering the active site of AGR2, providing valuable molecular insights for the toxicity profile of GQD nanomaterials.

A Magnetic Field Sensor Based on Directional Coupling in a Magnetic Fluid-Filled Photonic Crystal Fiber.

In this paper, a dual-core photonic crystal fiber (DC-PCF) sensitivity sensor filled with magnetic liquid is introduced and investigated with the finite element method (FEM). To regulate the energy coupling involving the two cores, the magnetic fluid is filled into the pore between the two cores. To adjust the coupling between the supermodes in the DC-PCF, the refractive index (RI) of the air hole filled magnetic fluid may change due to the external magnetic field. This specifically created a magnetic fluid-filled DC-PCF; the magnetic fluid-filled hole is not used as the core for energy transmission, thus avoiding transmission loss. The dip wavelength and the magnetic field displayed an excellent linear connection between 80 and 260 Oe, depending on the numerical data. The detection sensitivity of the magnetic field reached 515.75 pm/Oe at a short fiber length of 482 µm. The designed magnetic fluid-filled DC-PCF has high sensitivity and small volume and has great application prospects in magnetic field detection in the medical and industrial fields.

Acid/GSH Dual-Responsive Endosome Escape Dual Pro-drug Micelles Targeted Synergistic Treatment for A549/ADR.

The resistance of cancer cells to anticancer drugs has been recognized as one of the main reasons for chemotherapy failure. Multidrug combination therapy is one of the most effective ways to solve this problem. Therefore, in this article, we designed and synthesized a pH/GSH dual-responsive camptothecin/doxorubicin (CPT/DOX) dual pro-drug synergistic treatment system with the aim of overcoming the resistance of non-small cell lung cancer A549/ADR cells to DOX. The pro-drug cRGD-PEOz-S-S-CPT (cPzT) was obtained by linking CPT to poly(2-ethyl-2-oxazoline) (PEOz) with endosomal escape properties through a GSH-responsive disulfide bond and modifying it with the targeted peptide cRGD. The pro-drug mPEG-NH-N=C-DOX (mPX) was synthesized by attaching DOX to polyethylene glycol (PEG) through acid-sensitive hydrazone bonds. The dual pro-drug micelles cPzT/mPX configured according to the CPT/DOX mass ratio of 3:1 showed a strong synergistic therapeutic effect at IC50 with a combined therapy index CI = 0.49, far less than 1. Moreover, with the further improvement of the inhibition rate, the 3:1 ratio showed a stronger synergistic therapeutic effect than other ratios. The cPzT/mPX micelles not only had better targeted uptake ability but also showed a better therapeutic effect in both 2D and 3D tumor suppression assays relative to free CPT/DOX and significantly enhanced the penetration ability into solid tumors. In addition, the results of confocal laser scanning microscopy (CLSM) showed that cPzT/mPX could effectively overcome the resistance of A549/ADR cells to DOX by delivering DOX into the nucleus to exert its effect. Thus, this dual pro-drug synergistic therapy system combining targeting and endosomal escape ability provides a possible strategy to overcome tumor drug resistance.

Study on complications of osteoporosis based on network pharmacology.

Osteoporosis is a serious threat to human life. Guben Zenggu Granule is an empirical prescription for clinical treatment of osteoporosis. MC3T3-E1 cells are mouse osteogenic precursor cells with osteogenic differentiation, and are classic cells for studying bone metabolism and osteogenic mechanism, as well as mechanical stimulation sensitive cells. Therefore, it can be inferred that Guben Zenggu granule can repair MC3T3-E1 cells under continuous static pressure overload. This study aims to through the network of pharmacology and gene sequencing method, reveal thrift increase bone particles under the condition of continuous static pressure overload on osteogenesis mechanism of MC3T3-E1 cells. In the process of analysis, from a variety of 98 compounds was predicted in the database, a collection of 474 goals, a total of 29,164 difference between two groups of genes. Then, construction of composite targets between cells and predict targets and protein - protein interaction networks, and through the cluster analysis to further explore the relationship between the target. In addition, linkages between target proteins and cells were further identified using Gene Ontology (GO) and Pathways (KEGG Pathway). Finally, the repair effect of Guben Zenggu granule on MC3T3-E1 cells under continuous static pressure overload was verified through experiments, so as to accurately explain the pharmacodynamic mechanism of Traditional Chinese medicine.

Strategy evaluation and optimization with an artificial society toward a Pareto optimum.

Strategy evaluation and optimization in response to troubling urban issues has become a challenging issue due to increasing social uncertainty, unreliable predictions, and poor decision-making. To address this problem, we propose a universal computational experiment framework with a fine-grained artificial society that is integrated with data-based models. The purpose of the framework is to evaluate the consequences of various combinations of strategies geared towards reaching a Pareto optimum with regards to efficacy versus costs. As an example, by modeling coronavirus 2019 mitigation, we show that Pareto frontier nations could achieve better economic growth and more effective epidemic control through the analysis of real-world data. Our work suggests that a nation's intervention strategy could be optimized based on the measures adopted by Pareto frontier nations through large-scale computational experiments. Our solution has been validated for epidemic control, and it can be generalized to other urban issues as well.

Stable structures and superconducting properties of Ca-La-H compounds under pressure.

The calcium hydrides and lanthanum hydrides under high pressures have been reported to have good superconducting properties with high-TC. In this work, the structures and superconductivities of Ca-La-H ternary hydrides have been studied by genetic algorithm and density functional theory calculations. Our results show that at the pressure range of 100-300 GPa, the most stable structure of CaLaH12has aCmmmsymmetry, in which there is a H24hydrogen cage. It can be expected to have high possibility to be synthesized due to its large stability. Furthermore, the predictedTCof theCmmm-CaLaH12structure is about 140 K at 150 GPa, and when the pressure decreases to 30 GPa, the CaLaH12structure with aC2/msymmetry has a predictedTCof about 49 K. The CaLaH12is suggested to be a stable good superconductor with large stability and performs well at relatively low pressures.

Precise delivery of multi-stimulus-responsive nanocarriers based on interchangeable visual guidance.

Cancer treatment is imminent, and controlled drug carriers are an important development direction for future clinical chemotherapy. Visual guidance is a feasible means to achieve precise treatment, reduce toxicity and increase drug efficacy. However, the existing visual control methods are limited by imaging time-consuming, sensitivity and side effects. In addition, the ability of the carrier to respond to environmental stimuli in vivo is another difficulty that limits its application. Here, we propose a highly stimulus-responsive GC liposome with precise tracing and sensitive feedback capabilities. It combines magnetic resonance imaging and fluorescence imaging, and addresses the need for precise visualization by alternating imaging modalities. More importantly, GC liposomes are a carrier that can accumulate stimuli. In this paper, by tracking the fragmentation process of empty GC and drug-loaded D-GC liposomes, we confirm the synergistic effect between multiple stimuli, which can result in a more efficient drug release performance. Finally, in mice models we examined the GC liposome imaging approach and the D-GC + UV group guided by this visualization exhibited the highest tumor inhibition efficiency (6.85-fold). This study highlights the advantages of alternate visualization-guided and co-stimulation treatment strategies, and provides design ideas and potential materials for efficient and less toxic cancer treatments.

Series of High Magnetic Resonance-Guided Photoinduced Nanodelivery Systems for Precisely Improving the Efficiency of Cancer Therapy.

Nanochemotherapy is recognized as one of the most promising cancer treatment options, and the design of the carrier has a crucial impact on the final efficacy. To precisely improve the efficacy and reduce the toxicity, we combined the clinical contrast agent (Gd-DTPA) with a stimulus-sensitive o-nitrobenzyl ester and then prepared a series of nNBGD lipids by varying the carbon chain length of the hydrophobic group. The self-assembled nNBGD liposomes can be tracked by MRI to localize the aggregation of drug carriers in vivo, so as to prompt the application of light stimulation at the optimal time to facilitate the precise release of carriers at the lesion site. And the application potential of this strategy was verified with 88% tumor suppression effect in the 12NBGD-DOX+UV group. In addition, this paper emphasizes that small differences in structure can affect the overall performance of the carriers. By exploration of the differences in stability, drug loading, stimulus responsiveness, MRI imaging effect, and toxicity of the series of nNBGD carriers, the relationship between the length of the hydrophobic group of nNBGD lipids and the overall performance of the carriers is given, which provides experimental support and design reference for other carriers.

Study on superconducting Li-Se-H hydrides.

The structures, stabilities and superconducting properties of LiSeHn (n = 4-10) hydrides at 150-300 GPa were studied by the genetic algorithm (GA) and DFT calculation method. Three stable stoichiometries of LiSeH4, LiSeH6 and LiSeH10 were uncovered under high pressure. Four other metastable stoichiometries of LiSeH5, LiSeH7, LiSeH8, and LiSeH9 were also studied. By analyzing the electronic band structure and electronic density of states, C2 LiSeH4, Pmm2 LiSeH6 and C2 LiSeH10 were all found to be metal phases above 150 GPa. Electron-phonon coupling calculations showed that C2 LiSeH4 and Pmm2 LiSeH6 were promising superconductors. The predicted Tc values of C2 LiSeH4 and Pmm2 LiSeH6 were 77 K at 200 GPa and 111 K at 250 GPa, respectively.

Evaluating the mitigation strategies of COVID-19 by the application of the CO2 emission data through high-resolution agent-based computational experiments.

The negative consequences, such as healthy and environmental issues, brought by rapid urbanization and interactive human activities result in increasing social uncertainties, unreliable predictions, and poor management decisions. For instance, the Coronavirus Disease (COVID-19) occurred in 2019 has been plaguing many countries. Aiming at controlling the spread of COVID-19, countries around the world have adopted various mitigation and suppression strategies. However, how to comprehensively eva luate different mitigation strategies remains unexplored. To this end, based on the Artificial societies, Computational experiments, Parallel execution (ACP) approach, we proposed a system model, which clarifies the process to collect the necessary data and conduct large-scale computational experiments to evaluate the effectiveness of different mitigation strategies. Specifically, we established an artificial society of Wuhan city through geo-environment modeling, population modeling, contact behavior modeling, disease spread modeling and mitigation strategy modeling. Moreover, we established an evaluation model in terms of the control effects and economic costs of the mitigation strategy. With respect to the control effects, it is directly reflected by indicators such as the cumulative number of diseases and deaths, while the relationship between mitigation strategies and economic costs is built based on the CO2 emission. Finally, large-scale simulation experiments are conducted to evaluate the mitigation strategies of six countries. The results reveal that the more strict mitigation strategies achieve better control effects and less economic costs.

Sensitive and precise visually guided drug delivery nanoplatform with dual activation of pH and light.

Controlled-release drug carriers in cancer therapy are the most ideal way to reduce toxicity and improve drug efficacy. Since light stimulation is precise and operable, most multi-stimulation response carriers utilize phototherapy to enhance release efficiency. However, phototoxicity severely limits the application of phototherapy. Herein, we designed and synthesized a Cou-ONB lipid with sensitive fluorescence feedback and multi-stimulus response. COBL liposomes prepared from Cou-ONB lipids will passively aggregate at the tumor and guide phototherapy by fluorescence. More importantly, it can reflect the drug release effect in vivo through its own sensitive fluorescence changes, further enabling precise phototherapy and reducing phototoxicity. In this paper, the multi-stimulus superimposed response and precise fluorescence-guided performance of COBL liposomes were investigated at the molecular, liposome, cellular, and animal levels. Finally, tumor treatment experiments showed that the d-COBL-UV group had the best tumor suppression effect (5.3-fold). This paper highlights a real-time fluorescence-guided multi-stimulus superposition strategy and provides a design idea to precisely implement exogenous stimuli by displaying the degree of drug release, aiming to achieve less toxic and more efficient cancer therapy through timely and precise multi-stimulation. STATEMENT OF SIGNIFICANCE: Multi-stimulus responsive drug carriers have been extensively developed in the last decade. Visual guidance is an important tool to achieve precision medicine and precise control of drug release. However, the available visualization materials are more aimed at directing stimulation at the optimal moment. There is little discussion on when to stop exogenous stimulation and how to minimize the damage of stimulation to the patient. Here, we provide a Cou-ONB lipid that not only responds to multiple stimuli, but also provides sensitive feedback on its own dissociation with a fluorescent signal so that physicians can adjust exogenous stimuli in a timely manner. This paper provides insights to facilitate precision drug delivery systems, providing viable design ideas for precise, efficient, and less toxic cancer therapies.

Magnetic Resonance Imaging-Guided Multi-Stimulus-Responsive Drug Delivery Strategy for Personalized and Precise Cancer Treatment.

The emergence of nano-targeted controlled release liposomal drug carriers has provided a breakthrough in cancer therapy. However, their clinical efficacy is unsatisfactory, which is related to individualized differences in targeted drugs and poor in vivo release efficiency. In this paper, we prepared a class of personalized targeted and precisely controlled-release therapeutic drug carriers (GF liposomes) by co-assembling targeting and traceable o-nitrobenzyl ester lipids to propose a magnetic resonance imaging (MRI)-guided personalized in vivo targeted drug screening strategy and a multi-stimulus superimposed controlled-release strategy. Furthermore, by following the drug release process of drug-loaded liposomes (GF-D), it was found that these liposomes could rely on energy superposition to achieve more sensitive and efficient controlled drug release. In addition, the indispensable adjustment of liposome formulation for personalized MRI-based targeted therapy was verified by differential cellular uptake and in vivo magnetic resonance imaging. In the end, the 10.22-fold tumor suppression effect in the stimulus superposition group (GF-D-UV) indicates that the multi-stimulus cumulative response strategy and MRI-guided in vivo screening strategy can more effectively treat cancer. This contribution provides a concise and clever design idea for the future development of personalized precise and efficient clinical cancer therapies.

An MRI-guided targeting dual-responsive drug delivery system for liver cancer therapy.

The targeting dual-responsive drug delivery system was employed for cancer treatment as a positive strategy. Herein, Lactobionic acid (LA)-modified and non-modified UV/reduction dual-responsive molecules (10,10-NB-S-S-P-LA and 10,10-NB-S-S-P-OMe) were synthesized. Functional magnetic resonance imaging (MRI) contrast agent (12,12-NB-DTPA-Gd) was mixed with 10,10-NB-S-S-P-LA or 10,10-NB-S-S-P-OMe in the optimal ratio (3:1) to develop targeted empty liposomes (GNSPL) or non-targeted empty liposomes (GNSPM) with superior UV/reduction dual-responsiveness, biocompatibility and magnetic resonance imaging (MRI) performance. The drug-loaded liposomes (GNSPLD and GNSPMD) can keep stable in two weeks, and the drug cumulative release rate reached to the maximum under dual stimulation of ultraviolet (UV) and reducing agent (TCEP). The treatment with GNSPLD + UV significantly inhibited the growth and migration of cancer cells in vitro. The GNSPLD liposomes were more effectively accumulated in tumor site than GNSPMD liposomes, due to the targeting property of GNSPLD liposomes. The treatment with GNSPLD + UV showed a better therapeutic efficacy than Doxorubicin (DOX) in vivo, and almost no side effects during the treatment period. Thus, the MRI-guided targeting dual-responsive drug delivery system provided a reliable therapeutic strategy for treating liver cancer.

Endogenous reactive oxygen species burst induced and spatiotemporally controlled multiple drug release by traceable nanoparticles for enhancing antitumor efficacy.

Reactive oxygen species (ROS) are not only used as a therapeutic reagent in chemodynamic therapy (CDT), to stimulate the release of antineoplastic drugs, they can also be used to achieve a combined effect of CDT and chemotherapy to enhance anticancer effects. Herein, we synthesized a pH-responsive prodrug (PEG2k-NH-N-DOX), ROS-responsive prodrug (PEG2k-S-S-CPT-ROS), organic CDT agents (TPP-PEG2k-LND, TPP-PEG2k-TOS), and T1-enhanced magnetic resonance imaging contrast agents (Gd-DTPA-N16-16), and used them to encapsulate combrestatinA4 (CA4) to prepare traceable pH/ROS dual-responsive multifunctional nanoparticles (TLDCAG NPs) with endogenous ROS burst and spatiotemporally controlled multiple drug release ability. Firstly, TLDCAG NPs were accumulated in the tumor cell microenvironment via an enhanced permeability and retention (EPR) effect. Secondly, CA4 was released and specifically destroyed angiogenesis to facilitate the interaction between the tumor and the remaining TLDCG NPs. After accumulating in tumor cells, the TLDCG NPs could be destroyed under acidic conditions to quickly release doxorubicin (DOX), TPP-PEG2k-LND, and TPP-PEG2k-TOS. Thirdly, TPP-PEG2k-LND and TPP-PEG2k-TOS quickly targeted mitochondria, induced endogenous ROS bursts, reduced the mitochondrial membrane potential, and induced tumor cell apoptosis. Endogenous ROS can not only be used as a therapeutic reagent for CDT, but also can cut off the thioketal bond in PEG2k-S-S-CPT-ROS and release camptothecin (CPT). Finally, TLDCAG NPs were traced by magnetic resonance imaging (MRI). Furthermore, in vitro and vivo results indicate that the TLDCAG NPs have vigorous antitumor activity and negligible systemic toxicity. Therefore, the TLDCAG NPs provide an efficient strategy for enhancing antitumor efficacy.