Lysine-Polydopamine Nanocrystals Loaded with the Codrug Abemaciclib-Flurbiprofen for Oral Treatment of Cancer.

Nonsteroidal anti-inflammatory drugs (NSAIDs) combined with chemotherapeutic agents for the treatment of colorectal cancer (CRC) are a promising therapeutic strategy. NSAIDs can effectively boost the antitumor efficacy of chemotherapeutic agents by inhibiting the synthesis of COX-2. However, hazardous side effects and barriers to oral drug absorption are the main challenges for combination therapy with chemotherapeutics and NSAIDs. To address these issues, a safe and effective lysine-polydopamine@abemaciclib-flurbiprofen (Flu) codrug nanocrystal (Lys-PDA@AF NCs) was designed. Abemaciclib (Abe), a novel and effective inhibitor of the CDK4/6 enzyme, and Flu were joined to prepare Abemaciclib-Flu codrug (AF) by amide bonds, and then the AF was made into nanocrystals. Lysine-modified polydopamine was selected as a shell to encapsulate nanocrystals to enhance intestinal adhesion and penetration and lengthen the duration time of drugs in vivo. Nuclear magnetic resonance, Fourier transform infrared, Massspectrometry, X-ray photoelectron spectroscopy, Transmission electron microscopy, and drug loading were used to evaluate the physicochemical characteristics of the nanocrystals. In our study, Abe and Flu were released to exert their synergistic effect when the amide bond of AF was broken and the amide bond was sensitive to cathepsin B which is overexpressed in most tumor tissues, thus increasing the selectivity of the drug to the tumor. The results showed that Lys-PDA@AF NCs had higher cytotoxicity for CRC cell with an IC50 of 4.86 µg/mL. Additionally, pharmacokinetics showed that Abe and Flu had similar absorption rates in the Lys-PDA@AF NCs group, improving the safety of combination therapy. Meanwhile, in vivo experiments showed that Lys-PDA@AF NCs had excellent antitumor effects and safety. Overall, it was anticipated that the created Lys-PDA@AF NCs would be a potential method for treating cancer.

Ionic Liquid Transdermal Patches of Two Active Ingredients Based on Semi-Ionic Hydrogen Bonding for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to deformities and disabilities in patients. Conventional treatment focuses on delaying progression; therefore, new treatments are necessary. The present study reported a novel ionic liquid transdermal platform for efficient RA treatment, and the underlying mechanism was elucidated using FTIR, 1H-NMR, Raman, XPS, and molecular simulations. The results showed that the reversibility of the semi-ionic hydrogen bonding facilitated high drug loading and enhanced drug permeability. Actarit's drug loading had an approximately 11.34-times increase. The in vitro permeability of actarit and ketoprofen was improved by 5.46 and 2.39 times, respectively. And they had the same significant effect in vivo. Furthermore, through the integration of network pharmacology, Western blotting (WB), and radiology analyses, the significant osteoprotective effects of SIHDD-PSA (semi-ionic H-bond double-drug pressure-sensitive adhesive transdermal patch) were revealed through the modulation of the JAK-STAT pathway. The SIHDD-PSA significantly reduced paw swelling and inflammation in the rat model, and stimulatory properties evaluation confirmed the safety of SIHDD-PSA. In conclusion, these findings provide a novel approach for the effective treatment of RA, and the semi-ionic hydrogen bonding strategy contributes a new theoretical basis for developing TDDS.

A twofold interpenetrated two-dimensional zinc(II) coordination polymer for the highly sensitive detection of nitrofurantoin in aqueous medium.

A novel ZnII coordination polymer, namely, poly[{µ2-bis[4-(2-methyl-1H-imidazol-1-yl)phenyl]methanone-κ2N3:N3'}(µ2-5-bromobenzene-1,3-dicarboxylato-κ2O1:O3)zinc(II)], [Zn(C8H3BrO4)(C21H18N4O)]n or [Zn(Br-BDC)(MIPMO)]n, (I), has been synthesized by the solvothermal method using 5-bromoisophthalic acid (Br-H2BDC), bis[4-(2-methyl-1H-imidazol-1-yl)phenyl]methanone (MIPMO) and Zn(NO3)2·6H2O. Structure analysis showed that compound (I) displays twofold parallel interwoven sql nets. Fluorescence experiments confirmed that the compound can sensitively and selectively detect nitrofurantoin (NFT) in aqueous medium. In addition, the possible fluorescence quenching mechanisms of compound (I) toward NFT are investigated.

Design and Evaluation of a Dual-Sensitive In Situ Gel for the Controlled Release of Pranoprofen.

Currently, the marketed ophthalmic preparations of pranoprofen (PF) are mainly eye drops, but due to the special clearance mechanism of the eye and corneal reflex, the contact time between the drug and the focal site is short, most of the drug is lost, and the bioavailability is less than 5%. In the present study, an in situ gel eye drop containing no bacteriostatic agent and sensitive to temperature and ions was designed for delivery of PF. It was demonstrated to meet the criteria for ophthalmic preparations by characterization such as appearance content sterility. Ocular irritation tests showed a favorable safety profile. In vivo ocular retention time experiments showed that the ocular retention time of the pranoprofen gel was 4.41 times longer than that of commercially available drops (Pranopulin®), and the nasal tear excretion of the pranoprofen gel was lower than that of Pranopulin®, which suggests that the drug loss was reduced relative to that of the drops. The efficacy of the pranoprofen gel against tincture of cayenne pepper-induced corneal and conjunctival inflammation was examined using Pranopulin® as a control and in conjunction with inflammation scores, H&E slice results, and levels of IL-1ß, IL-6, and TNF-α. The results showed that pranoprofen gel and Pranololin® had significant efficacy in the treatment of corneal and conjunctival inflammation, and the anti-inflammatory effect of pranoprofen gel was superior to that of Pranololin®. This study provides a new option for the treatment of corneal and conjunctival inflammation.

Co-delivery of Brinzolamide and Timolol from Micelles-laden Contact Lenses: In vitro and In Vivo Evaluation.

PURPOSE: Traditional eye drops exhibit a modest bioavailability ranging from 1 to 5%, necessitating recurrent application. Thus, a contact lens-based drug delivery system presents substantial benefits. Nonetheless, pharmaceutical agents exhibiting poor solubility may compromise the quintessential characteristics of contact lenses and are, consequently, deemed unsuitable for incorporation. To address this issue, the present study has engineered a novel composite drug delivery system that amalgamates micellar technology with contact lenses, designed specifically for the efficacious conveyance of timolol and brinzolamide. METHODS: Utilizing mPEG-PCL as the micellar material, this study crafted mPEG-PCL micelles loaded with brinzolamide and timolol through the film hydration technique. The micelle-loaded contact lens was fabricated employing the casting method; a uniform mixture of HEMA and EGDMA with the mPEG-PCL micelles enshrouding brinzolamide and timolol was synthesized. Following the addition of a photoinitiator, 50 µL of the concoction was deposited into a contact lens mold. Subsequently, the assembly was subjected to polymerization under 365 nm ultraviolet light for 35 min, resulting in the formation of the micelle-loaded contact lenses. RESULTS: In the present article, we delineate the construction of a micelle-loaded contact lens designed for the administration of brinzolamide and timolol in the treatment of glaucoma. The study characterizes crucial properties of the micelle-loaded contact lenses, such as transmittance and ionic permeability. It was observed that these vital attributes meet the standard requirements for contact lenses. In vitro release studies revealed that timolol and brinzolamide could be gradually liberated over periods of up to 72 and 84 h, respectively. In vivo pharmacodynamic evaluation showed a significant reduction in intraocular pressure and a relative bioavailability of 10.84 times that of commercially available eye drops. In vivo pharmacokinetic evaluation, MRT was significantly increased, and the bioavailability of timolol and brinzolamide was 2.71 and 1.41 times that of eye drops, respectively. Safety assessments, including in vivo irritation, histopathological sections, and protein adsorption studies, were conducted as per established protocols, confirming that the experiments were in compliance with safety standards. IN CONCLUSION: The manuscript delineates the development of a safe and efficacious micelle-loaded contact lens drug delivery system, which presents a novel therapeutic alternative for the management of glaucoma.

Applications and recent advances in transdermal drug delivery systems for the treatment of rheumatoid arthritis.

Rheumatoid arthritis is a chronic, systemic autoimmune disease predominantly based on joint lesions with an extremely high disability and deformity rate. Several drugs have been used for the treatment of rheumatoid arthritis, but their use is limited by suboptimal bioavailability, serious adverse effects, and nonnegligible first-pass effects. In contrast, transdermal drug delivery systems (TDDSs) can avoid these drawbacks and improve patient compliance, making them a promising option for the treatment of rheumatoid arthritis (RA). Of course, TDDSs also face unique challenges, as the physiological barrier of the skin makes drug delivery somewhat limited. To overcome this barrier and maximize drug delivery efficiency, TDDSs have evolved in terms of the principle of transdermal facilitation and transdermal facilitation technology, and different generations of TDDSs have been derived, which have significantly improved transdermal efficiency and even achieved individualized controlled drug delivery. In this review, we summarize the different generations of transdermal drug delivery systems, the corresponding transdermal strategies, and their applications in the treatment of RA.

Contact lens as an emerging platform for ophthalmic drug delivery: A systematic review.

The number of people with eye diseases has increased with the use of electronics. However, the bioavailability of eye drops remains low owing to the presence of the ocular barrier and other reasons. Although many drug delivery systems have been developed to overcome these problems, they have certain limitations. In recent years, the development of contact lenses that can deliver drugs for long periods with high bioavailability and without affecting vision has increased the interest in using contact lenses for drug delivery. Hence, a review of the current state of research on drug delivery contact lenses has become crucial. This article reviews the key physical and chemical properties of drug-laden contact lenses, development and classification of contact lenses, and features of the commonly used materials. A review of the methods commonly used in current research to create contact lenses has also been presented. An overview on how drug-laden contact lenses can overcome the problems of high burst and short release duration has been discussed. Overall, the review focuses on drug delivery methods using smart contact lenses, and predicts the future direction of research on contact lenses.

ROS/pH dual-sensitive emodin-chlorambucil co-loaded micelles enhance anti-tumor effect through combining oxidative damage and chemotherapy.

The high level of reactive oxygen species (ROS) at the tumor site has been widely used in the tumor targeted delivery. However, the ROS stimulus-responsive vector itself is also a ROS consumer, and the consumption of endogenous ROS may not be sufficient to maintain sustained drug release. In this study, we designed and synthesized ROS/pH dual-sensitive polymer micelles for the co-delivery of emodin (EMD) and chlorambucil (CLB). The release of quinone methides (QM) can consume glutathione (GSH), on the one hand, it can enhance the chemotoxicity of phenylbutyrate nitrogen mustard, on the other hand, emodin can induce oxidative damage of tumor cells and maintain the sustained targeted release of drugs.

A ROS-response hyaluronic acid-coated/chitosan polymer prodrug for enhanced tumour targeting efficacy of SN38.

Ethyl-10-hydroxycamptothecin (SN38) is a camptothecin derivative with significant anti-tumour therapeutic potential, while the clinical application of SN38 was limited by its poor water solubility and low stability. Herein, a core-shell polymer prodrug hyaluronic acid @chitosan-S-SN38 (HA@CS-S-SN38) was designed by CS-S-SN38 as the core and the HA as the shell, which aims to overcome the limitations of the clinical application of SN38, while realising the high tumour targeting of polymer prodrug and the controllable release of drug in tumour cells. HA@CS-S-SN38 showed the high responsiveness of the tumour microenvironment and the safe stability of blood circulation. Furthermore, HA@CS-S-SN38 exhibited the begin uptake efficiency and favourable apoptosis in the 4T1 cells. More importantly, compared with irinotecan hydrochloride trihydrate (CPT-11), HA@CS-S-SN38 significantly improved the conversion efficiency of the prodrug to SN38, and showed excellent tumour targeting and retention in vivo by combining passive and active targeting strategies. In tumour-bearing mice treatment, HA@CS-S-SN38 showed the perfect anti-tumour effect and therapeutic safety. These results indicated that the polymer prodrug designed by ROS-response/HA-modification strategy is a safe and efficient drug delivery system, which provides a new idea for clinical utilisation of SN38 and warrants further evaluation.

Contextual Instance Decoupling for Instance-Level Human Analysis.

One fundamental challenge of instance-level human analysis is to decouple instances in crowded scenes, where multiple persons are overlapped with each other. This paper proposes the Contextual Instance Decoupling (CID), which presents a new pipeline of decoupling persons for multi-person instance-level analysis. Instead of relying on person bounding boxes to spatially differentiate persons, CID decouples persons in an image into multiple instance-aware feature maps. Each of those feature maps is hence adopted to infer instance-level cues for a specific person, e.g., keypoints, instance mask or part segmentation masks. Compared with bounding box detection, CID is differentiable and robust to detection errors. Decoupling persons into different feature maps also allows to isolate distractions from other persons, and explore context cues at scales larger than the bounding box size. Extensive experiments on various tasks including multi-person pose estimation, person foreground segmentation, and part segmentation, show that CID consistently outperforms previous methods in both accuracy and efficiency. For instance, it achieves 71.3% AP on CrowdPose in multi-person pose estimation, outperforming the recent single-stage DEKR by 5.6%, the bottom-up CenterAttention by 3.7%, and the top-down JC-SPPE by 5.3%. This advantage sustains on multi-person segmentation and part segmentation tasks.

Complex Three-Dimensional Terrains Traversal of Insect-Scale Soft Robot.

This article proposes a piezoelectric-driven insect-scale soft robot with ring-like curved legs, enabling it to traverse complex three-dimensional (3D) terrain only by body-terrain mechanical action. Relying on the repeated deformation of the main body's n and u shapes, the robot's leg-ground mechanical action produces an "elastic gait" to move. Regarding the detailed design, first, a theoretical curve of the front leg with a fixed angle of attack of 75° is designed by finite element simulation and comparative experiments. It ensures no increase in drag and no decrease in the lift when climbing steps. Second, a ring-like leg structure with 100% closed degree is proposed to ensure a smooth pass through small-sized uneven terrain without getting stuck. Then, the design of the overall asymmetrical structure of the robot can improve the conversion ratio of vibration to forward force. The shape of curved legs is controlled by pulling the flexible leg structure with two metal wires working as spokes. The semirigid leg structure made of fully flexible materials has shape stability and structural robustness. Compared with the plane-legged robot, the curved-legged robot can smoothly traverse different rugged 3D terrains and cross the terrain covering obstacles 0.36 times body height (BH) at a speed of >4 body lengths per second. Moreover, the curved-legged robot shows 100% and 64% chances of climbing steps with 1.2- and 1.9-times BH, respectively.

Glycyrrhetinic acid modified chlorambucil prodrug for hepatocellular carcinoma treatment based on DNA replication and tumor microenvironment.

Chlorambucil (CLB) is widely used in the treatment of solid tumors. However, CLB has poor water solubility, short half-life and side effects such as leucopenia and thrombocytopenia, in addition to the inhibition of tumor immune microenvironment. In our study, chlorambucil-chitosan (CLB-CS) prodrug micelles were successfully prepared, and glycyrrhetinic acid (GA) was selected, which could improve the immunosuppressive microenvironment and actively targeted liver cancer cells. At the tumor site, CLB blocked the cell cycle and promoted apoptosis. In addition, GA improved the tumor microenvironment by increasing the proportion of CD4+T and CD8+T cells at the tumor site, and promoting the differentiation of CD4+T cells into Th1 cells, thereby reducing the proportion of Treg and Th2 cell subsets, so as to offset the adverse factors of CLB against tumor immunity. By interfering with DNA replication and modulating the tumor microenvironment, GA/CLB-CS micelles enabled the effective treatment of liver cancer.

Dual-responsive nanovaccine for cytosolic delivery of antigens to boost cellular immune responses and cancer immunotherapy.

Cancer vaccine contributing to the success of the treatment and prevention of tumors has attracted a huge attention as a strategy for tumor immunotherapy in recent years. A major challenge of cancer vaccine is to target cytosols of dendritic cells (DCs) in the lymph nodes (LNs) to enhance efficiency of antigen cross-presentation, which elicits high levels of cytotoxic T-lymphocytes to destruct tumor cells. Here, we address this issue by conjugating ovalbumin (OVA) to PEG-PCL using disulfide bond (-ss-), and the degradable pH-responsive polymer-PEI-PCL as delivery carrier. In addition, the mol ratio of PEG-PCL to PEI-PCL in the mixed micelles was tailored to deliver the OVA to LNs. Subsequently, CpG ODN1826, a TLR-9 agonist, was further introduced into a mixed micelle of 30 nm or less as a unique tumor vaccine. Importantly, the results demonstrated the mixed micelles with 1:1 mol of PCL-PEG and PCL-PEI can effectively migrate to distal LNs where antigen were efficiently captured by DCs, meanwhile, OVA was modified to the surface of mixed micelles via disulfide bonds (-ss-) for promotion efficiency of antigen cross-presentation. More surprisingly, combination of tumor vaccine with anti-PD-1, the therapy of ectopic melanoma (B16-OVA) and lung metastasis melanoma (B16-OVA) is excellent therapeutic effect. Taken together, our works offers a novel strategy for the cytosol delivery of antigens to achieve potent cancer immunotherapy.

New Self-Repairing System for Brittle Matrix Composites Using Corrosion-Induced Intelligent Fiber.

Brittle matrix composites such as concrete are susceptible to damage in the form of cracks. Most of the current self-repair and self-healing techniques have repair limits on crack widths or high costs of an external stimulator, or have an unfavorable effect on the composite's strength. This paper proposes a new concept of corrosion-induced intelligent fiber (CIF) and a new self-repairing system that uses the CIFs to close cracks in brittle matrix composites within a corrosive environment without external help, and without compromising the strength. The CIF comprises an inner core fiber and an outer corrodible coating that are in equilibrium, with the core fiber in tension and the corrodible coating in compression. The preparation steps and shape recovery mechanism of the CIF and the self-repair mechanism of the CIF composites are explained. Based on these concepts, this paper also describes several mechanical models built to predict the magnitude of pre-stress stored in the core fiber, and the maximum pre-stress released to the matrix composites, and the minimum length of the reliable anchor ends of CIF. The sample calculation results show that the recovery strain was 0.5% for the CIF with the steel core fiber and 12.7% for the CIF with the nylon core fiber; the maximum crack closing force provided by the CIF to concrete can be increased by increasing the amount of the CIFs in concrete and the initial tensile stress of the core fiber. This paper provides some suggestions for enhancing the self-repair capability of brittle composites in complex working environments.

Fe-Catalyzed Selective Formal Insertion of Diazo Compounds into C(sp)-C(sp3) Bonds of Propargyl Alcohols: Access to Alkyne-Substituted All-Carbon Quaternary Centers.

The construction of all-carbon quaternary centers, especially those containing an alkyne-substituted framework, represents an important challenge in organic synthesis. Here we present a novel Fe-catalyzed selective formal insertion of diazo compounds into C(sp)-C(sp3) bonds of propargyl alcohols under mild conditions that enables the streamlined construction of alkyne-substituted all-carbon quaternary centers. This unique strategy starts with in situ generation of an ester group in the presence of carboxylic acids, followed by insertion of metal-carbene into C(sp)-C(sp3) bonds, which may open up a new reaction mode for exploring metal-carbene insertion into acyclic C-C bonds.

Monitoring the Early Strength Development of Cement Mortar with Piezoelectric Transducers Based on Eigenfrequency Analysis Method.

Monitoring the early strength formation process of cement is of great importance for structural construction management and safety. In this study, we investigated the relationship between the eigenfrequency and the early strength development of cement mortar. Embedded piezoceramic-based smart aggregates recorded the early strength of cement mortar. An eigenfrequency analysis model demonstrated the relationship between strength and frequency. Experiments were performed by using piezoelectric transducers to monitor the early strength formation process during the testing period. Three types of specimens with different strength grades were tested, and the early strength formation processes were recorded. The experimental results demonstrate that cement mortar strength has a good linear relationship with the resonance frequency, and the average square of the correlation coefficient is greater than 0.98. The results show that structural health monitoring technology is a feasible method of assessing structural safety conditions and has a broad market in the structural construction industry.

Hybrid micelles loaded with chemotherapeutic drug-photothermal agent realizing chemo-photothermal synergistic cancer therapy.

The synergistic therapy of malignant tumors with chemotherapy and photothermal therapy has attracted extensive researcher attention. With the further development of photosensitizers, photosensitizer delivery and stability are the urgent problem to be solved at present. In this study, the biodegradable hybrid micelles (HMs) nano system for co-delivery paclitaxel (PTX) and IR825, investigating the photosensitizer stability in the drug delivery system and therapeutic effectiveness in vitro or in vivo. The hybrid micelle (PTX/IR825-TAT HMs) was self-assembled through hydrophobic interactions between polyethyleneimine-polycaprolactone (PEI-PCL) and TAT peptide modifided-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(polyethylene glycol)5000 (TAT-PEG-DSPE). The results indicated that TAT HMs could successfully encapsulate IR825 PTX (PTX/IR825-TAT HMs). More importantly, IR825 encapsulated in hybrid micelles improved physiological stability, thermostability and photostability. In addition, the PTX released rapidly from PTX/IR825-TAT HMs in acidic and laser irradiation environments. In vitro cell analysis demonstrated that PTX/IR825-TAT HMs exhibited effective internalization of breast cancer cells. At the same time, PTX/IR825-TAT HMs with laser irradiation synergistically induced cancer cell apoptosis and death. indicating chemo-photothermal therapy synergistic therapeutic effect. In vivo antitumor studies showed that PTX/IR825-TAT HMs precisely reached the tumor tissue and convert light energy into heat energy under laser irradiation, PTX/IR825-TAT HMs had excellent synergistic antitumor efficiency compared to single chemotherapy and photothermal therapy.

Codelivery of Shikonin and siTGF-ß for enhanced triple negative breast cancer chemo-immunotherapy.

Although chemoimmunotherapy has achieved considerable success in cancer treatment in recent years, the cure for triple-negative breast cancer (TNBC) remains elusive. The unsatisfied outcomes are likely attributed to deficient tumor immunogenicity, a strong immunosuppressive tumor microenvironment (ITM) and tumor metastasis. To address this issue, we constructed an effective codelivery system, combined with tumor growth factor ß (TGF-ß) small interference RNA (siTGF-ß) and shikonin (SK), to achieve successful chemoimmunotherapy of TNBC. The SK/siTGF-ß NPs (approximately 110 nm) exhibited a uniform structure and good stability. Conjugated FA presented enhanced cellular uptake in 4T1 cells, and siTGF-ß escaped from lysosomes because of the "proton sponge" effect of PEI. Furthermore, SK actually induced satisfactory immunogenic cell death (ICD) and the resulting dendritic cell (DC) maturation facilitated a distinctly enhanced cytotoxic T lymphocyte (CTL) response, generating a positive effect on tumor suppression. Simultaneously, the successful silencing of TGF-ß alleviated the TGF-ß-mediated ITM and inhibited the epithelial-to-mesenchymal transition (EMT), contributing to the infiltration of CTLs, suppression of regulatory T lymphocyte (Treg) proliferation and lung metastasis inhibition. Thus, the SK/siTGF-ß NPs demonstrated the strongest therapeutic effect with delayed tumor growth (TIR = 88.5%) and lung metastasis restraint (77.3%). More importantly, tumor rechallenge assay suggested that the codelivery system produced a long-term immunological memory response to prevent tumor recurrence. Based on boosting the immune response and combating the ITM, SK/siTGF-ß NPs would be a potential approach for TNBC therapy.

Synergistic chemo-photothermal cancer therapy of pH-responsive polymeric nanoparticles loaded IR825 and DTX with charge-reversal property.

IR825 is a kind of near-infrared (NIR) small molecule cyanine dye and has distinct near-infrared absorbance and excellent thermal conversion performance. Due to poor stability and insufficient therapy efficacy, various nano-systems have been developed as delivery vehicles for NIR dyes to improve their application in tumor treatment. Herein, we developed an intelligent polymer drug vehicle (Mal-PAH-PEG-DMMA/ poly (ethylene imine) - poly(ε-caprolactone) block polymers, MPPD/PEI-PCL) based on pH-responsive charge-reversal to deliver docetaxel (DTX) and photosensitizer (IR825) for chemo-photothermal combination therapy (MPPD@IR825/DTX NPs). MPPD@IR825/DTX NPs could undergo charge conversion in a slightly acidic microenvironment (pH 6.8), resulted in strong electrostatic repulsion to withdraw the shell of the polymer nanoparticles (MPPD), enhanced cellular uptake and increased drug release. MPPD@IR825/DTX NPs demonstrated nanoscale in size with good mono-dispersity and stability, triggered DTX release in response to acid environment and NIR stimulation, in the same time providing excellent photothermal conversion efficiency. In vitro and In vivo experiments confirmed that charge-reversal polymeric nanoparticles improved antitumor efficiency in 4T1 tumor cell modal than non-charge-reversal polymeric nanoparticles. Furthermore, in comparison with chemotherapy or photothermal therapy in a single treatment mode, chemo-photothermal combination therapy of MPPD@IR825/DTX NPs with laser irradiation showed highly efficient tumor ablation. In addition, the polymeric nanoparticles exhibited good biocompatibility and safety. Therefore, the design of charge-reversal polymeric nanoparticles (MPPD@IR825/DTX NPs) provides a new strategy and promising application for targeting and synergistic chemo-photothermal combination therapy.

Facile Fabrication of Multilayer Stretchable Electronics via a Two-mode Mechanical Cutting Process.

A time- and cost-effective fabrication methodology via a two-mode mechanical cutting process for multilayer stretchable electronics has been developed without using the conventional photolithography-based processes. A commercially available vinyl cutter is used for defining complex patterns on designated material layers by adjusting the applied force and the depth of the cutting blade. Two distinct modes of mechanical cutting can be achieved and employed to establish the basic fabrication procedures for common features in stretchable electronics, such as the metal interconnects, contact pads, and openings by the "tunnel cut" mode, and the flexible overall structure by the "through cut" mode. Three robust and resilient stretchable systems have been demonstrated, including a water-resistant, omnidirectionally stretchable supercapacitor array, a stretchable mesh applicable in sweat extraction and sensing, and a skin-mountable human breathing monitoring patch. Results show excellent electronic performances of these devices made of multilayer functional materials after repetitive large deformations.