High Capacity, Dendrite-Free Growth, and Minimum Volume Change Na Metal Anode.

Na metal anode attracts increasing attention as a promising candidate for Na metal batteries (NMBs) due to the high specific capacity and low potential. However, similar to issues faced with the use of Li metal anode, crucial problems for metallic Na anode remain, including serious moss-like and dendritic Na growth, unstable solid electrolyte interphase formation, and large infinite volume changes. Here, the rational design of carbon paper (CP) with N-doped carbon nanotubes (NCNTs) as a 3D host to obtain Na@CP-NCNTs composites electrodes for NMBs is demonstrated. In this design, 3D carbon paper plays a role as a skeleton for Na metal anode while vertical N-doped carbon nanotubes can effectively decrease the contact angle between CP and liquid metal Na, which is termed as being "Na-philic." In addition, the cross-conductive network characteristic of CP and NCNTs can decrease the effective local current density, resulting in uniform Na nucleation. Therefore, the as-prepared Na@CP-NCNT exhibits stable electrochemical plating/stripping performance in symmetrical cells even when using a high capacity of 3 mAh cm-2 at high current density. Furthermore, the 3D skeleton structure is observed to be intact following electrochemical cycling with minimum volume change and is dendrite-free in nature.

Inorganic-Organic Coating via Molecular Layer Deposition Enables Long Life Sodium Metal Anode.

Metallic Na anode is considered as a promising alternative candidate for Na ion batteries (NIBs) and Na metal batteries (NMBs) due to its high specific capacity, and low potential. However, the unstable solid electrolyte interphase layer caused by serious corrosion and reaction in electrolyte will lead to big challenges, including dendrite growth, low Coulombic efficiency and even safety issues. In this paper, we first demonstrate the inorganic-organic coating via advanced molecular layer deposition (alucone) as a protective layer for metallic Na anode. By protecting Na anode with controllable alucone layer, the dendrites and mossy Na formation have been effectively suppressed and the lifetime has been significantly improved. Moreover, the molecular layer deposition alucone coating shows better performances than the atomic layer deposition Al2O3 coating. The novel design of molecular layer deposition protected Na metal anode may bring in new opportunities to the realization of the next-generation high energy-density NIBs and NMBs.

Safe and Durable High-Temperature Lithium-Sulfur Batteries via Molecular Layer Deposited Coating.

Lithium-sulfur (Li-S) battery is a promising high energy storage candidate in electric vehicles. However, the commonly employed ether based electrolyte does not enable to realize safe high-temperature Li-S batteries due to the low boiling and flash temperatures. Traditional carbonate based electrolyte obtains safe physical properties at high temperature but does not complete reversible electrochemical reaction for most Li-S batteries. Here we realize safe high temperature Li-S batteries on universal carbon-sulfur electrodes by molecular layer deposited (MLD) alucone coating. Sulfur cathodes with MLD coating complete the reversible electrochemical process in carbonate electrolyte and exhibit a safe and ultrastable cycle life at high temperature, which promise practicable Li-S batteries for electric vehicles and other large-scale energy storage systems.

Atomic layer deposition of lithium phosphates as solid-state electrolytes for all-solid-state microbatteries.

Atomic layer deposition (ALD) has been shown as a powerful technique to build three-dimensional (3D) all-solid-state microbattery, because of its unique advantages in fabricating uniform and pinhole-free thin films in 3D structures. The development of solid-state electrolyte by ALD is a crucial step to achieve the fabrication of 3D all-solid-state microbattery by ALD. In this work, lithium phosphate solid-state electrolytes were grown by ALD at four different temperatures (250, 275, 300, and 325 °C) using two precursors (lithium tert-butoxide and trimethylphosphate). A linear dependence of film thickness on ALD cycle number was observed and uniform growth was achieved at all four temperatures. The growth rate was 0.57, 0.66, 0.69, and 0.72 Å/cycle at deposition temperatures of 250, 275, 300, and 325 °C, respectively. Furthermore, x-ray photoelectron spectroscopy confirmed the compositions and chemical structures of lithium phosphates deposited by ALD. Moreover, the lithium phosphate thin films deposited at 300 °C presented the highest ionic conductivity of 1.73 × 10(-8) S cm(-1) at 323 K with ~ 0.51 eV activation energy based on the electrochemical impedance spectroscopy. The ionic conductivity was calculated to be 3.3 × 10(-8) S cm(-1) at 26 °C (299 K).

Intraperitoneal administration of doxorubicin-encapsulated Brucea javanica oil nanoemulsion against malignant ascites.

Malignant ascites is a common complication of advanced cancers, which reduces survival rates and diminishes patients' quality of life. Intraperitoneal chemotherapy is a conventional method for treating cancer-related ascites, but the poor drug retention of conventional drugs requires frequent administration to maintain sustained anti-tumor effects. In this study, we encapsulated doxorubicin (DOX) into Brucea javanica oil (BJO) to develop a water-in-oil (W/O) nanoemulsion called BJO@DOX for the treatment of malignant ascites through in-situ intraperitoneal administration. BJO significantly induced apoptosis of S180 cells by upregulating the expression of p53 and caspase-3 (cleaved). Additionally, BJO notably downregulated the expression of Bcl-2, further promoting apoptosis of S180 cells. Cell apoptosis significantly inhibited ascites formation and tumor cell proliferation in a mouse model. The combination of DOX and BJO exhibited satisfactory synergistic effects, consequently prolonging the survival period of mice. Histological examination of major organs indicated that the nanoemulsion had excellent biosafety in vivo. The BJO@DOX nanoemulsion represents a promising platform for in-situ chemotherapy of malignant ascites.

An oral bioactive chitosan-decorated doxorubicin nanoparticles/bacteria bioconjugates enhance chemotherapy efficacy in an in-situ breast cancer model.

Breast cancer is the second leading cause of cancer-related deaths among women worldwide. Despite significant advancements in chemotherapy, its effectiveness is often limited by poor drug distribution and systemic toxicity caused by the weak targeting ability of conventional therapeutic agents. The hypoxic tumor microenvironment (TME) also plays a vital role in treatment outcomes. Oral anticancer therapeutic agents have gained popularity and show promising results due to their ease of repeated administration. This study introduces autopilot biohybrids (Bif@BDC-NPs) for the effective delivery of doxorubicin (DOX) to the tumor site. This hybrid combines albumin-encapsulated DOX nanoparticles (BD-NPs) coated with chitosan (CS) for breast cancer chemotherapy, along with anaerobic Bifidobacterium infantis (B. infantis, Bif) serving as self-propelled motors. Due to Bif's specific anaerobic properties, Bif@BDC-NPs precisely anchor hypoxic regions of tumor tissue and significantly increase drug accumulation at the tumor site, thereby promoting tumor cell death. In an in-situ mouse breast cancer model, Bif@BDC-NPs achieved 94 % tumor inhibition, significantly prolonging the median survival of mice to 62 days, and reducing the toxic side effects of DOX. Therefore, the new bacteria-driven oral drug delivery system, Bif@BDC-NPs, overcomes multiple physiological barriers and holds great potential for the precise treatment of solid tumors.

Intraperitoneal administration of thermosensitive hydrogel Co-loaded with norcantharidin nanoparticles and oxaliplatin inhibits malignant ascites of hepatocellular carcinoma.

Malignant ascites is a common complication of some advanced cancers. Although intraperitoneal (IP) administration of chemotherapy drugs is routinely used to treat cancerous ascites, conventional drugs have poor retention and therefore need to be administered frequently to maintain a sustained anti-tumor effect. In this study, a thermosensitive hydrogel composite loaded with norethindrone nanoparticles (NPs) and oxaliplatin (N/O/Hydrogel) was developed to inhibit ascites of hepatocellular carcinoma (HCC) through IP injection. N/O/Hydrogel induced apoptosis in the H22 cells in vitro, and significantly inhibited ascites formation, tumor cell proliferation and micro-angiogenesis in a mouse model of advanced HCC with ascites, and prolonged the survival of tumor-bearing mice. Histological examination of the major organs indicated that the hydrogel system is safe. Taken together, the N/O/Hydrogel system is a promising platform for in-situ chemotherapy of malignant ascites.

Injectable hydrogel loaded with paclitaxel and epirubicin to prevent postoperative recurrence and metastasis of breast cancer.

Post-operative recurrence and metastasis is a major challenge for breast cancer treatment. Local chemotherapy is a promising strategy that can overcome this problem. In this study, we synthesized an injectable hyaluronic acid (HA)-based hydrogel loaded with paclitaxel (PTX) nanoparticles and epirubicin (EPB) (PPNPs/EPB@HA-Gel). PPNPs/EPB@HA-Gel steadily released the encapsulated drugs to achieve long-term inhibition of tumor recurrence and metastasis in a murine post-operative breast tumor model, which prolonged their survival without any systemic toxicity. The drug-loaded hydrogel inhibited the proliferation and migration of tumor cells in vitro, and significantly increased tumor cell apoptosis in vivo. Therefore, PPNPs/EPB@HA-Gel can be used as a local chemotherapeutic agent to prevent postoperative recurrence and metastasis of breast cancer.

Erythrocyte membrane-camouflaged gefitinib/albumin nanoparticles for tumor imaging and targeted therapy against lung cancer.

Conventional chemotherapeutic drugs may cause serious side effects such as hepatotoxicity and renal toxicity due to lack of targeting, which affects therapy outcome and the prognosis of patients. Therefore, biomimetic nanoparticles with long blood circulation and active targeting have attracted increasing attention. In this work, we fabricated a biomimetic R-RBC@GEF-NPs nano-system by encapsulating gefitinib-loaded albumin nanoparticles (GEF-NPs) inside cRGD-modified red blood cell (RBC) membranes. The complete RBC membrane structure and membrane proteins enabled the NPs to escape phagocytosis by macrophages. In addition, the cRGD moiety significantly improved tumor cell targeting and uptake. R-RBC@GEF-NPs inhibited the growth of A549 cells in vitro in a dose- and time-dependent manner by inducing apoptosis and cell cycle arrest at the G1 phase. Likewise, the R-RBC@GEF-NPs also decreased tumor weight and volume in the mice injected with A549 cells and prolonged survival time. In addition, the 99Tc-labeled R-RBC@GEF-NPs selectively accumulated in the tumor tissues in vivo, and enabled real time tumor imaging. Finally, blood and histological analyses showed that R-RBC@GEF-NPs did not cause any obvious systemic toxicity. Taken together, the biomimetic R-RBC@GEF-NPs is a promising therapeutic formulation for the treatment of lung cancer.

Patient-Derived Organoids Can Guide Personalized-Therapies for Patients with Advanced Breast Cancer.

Most breast cancers at an advanced stage exhibit an aggressive nature, and there is a lack of effective anticancer options. Herein, the development of patient-derived organoids (PDOs) is described as a real-time platform to explore the feasibility of tailored treatment for refractory breast cancers. PDOs are successfully generated from breast cancer tissues, including heavily treated specimens. The microtubule-targeting drug-sensitive response signatures of PDOs predict improved distant relapse-free survival for invasive breast cancers treated with adjuvant chemotherapy. It is further demonstrated that PDO pharmaco-phenotyping reflects the previous treatment responses of the corresponding patients. Finally, as clinical case studies, all patients who receive at least one drug predicate to be sensitive by PDOs achieve good responses. Altogether, the PDO model is developed as an effective platform for evaluating patient-specific drug sensitivity in vitro, which can guide personal treatment decisions for breast cancer patients at terminal stage.

Co-delivery of paclitaxel and curcumin by biodegradable polymeric nanoparticles for breast cancer chemotherapy.

Multi-drug chemotherapy has been one of the most popular strategies for the treatment of malignant tumors, and has achieved desirable therapeutic outcomes. The objective of the present study is to develop biodegradable PCEC nanoparticles (NPs) for the co-delivery of paclitaxel (PTX) and curcumin (CUR), and investigate the antitumor effect of the drug delivery system (DDS: PTX-CUR-NPs) against breast cancer both in vitro and in vivo. The prepared PTX-CUR-NPs had a small size of 27.97 ± 1.87 nm with a low polydispersity index (PDI, 0.197 ± 0.040). The results exhibited slow release of PTX and CUR from the DDS without any burst effect. Further, the PTX-CUR-NPs displayed a dose-dependent cytotoxicity in MCF-7 cells with a higher apoptosis rate (64.29% ± 1.97%) as compared to that of free drugs (PTX + CUR, 34.21% ± 0.81%). The cellular uptake study revealed that the drug loaded PCEC polymeric nanoparticles were more readily uptaken by tumor cells in vitro. To evaluate the in vivo anti-tumor effect, the PTX-CUR-NPs were intravenously administered to BALB/c nude mouse xenografted with MCF-7 cells and the results exhibited significant inhibition of tumor growth with prolonged survival time and reduced side effect when compared with free drugs (PTX + CUR). Moreover, the administration of PTX-CUR-NPs treatment led to lower Ki67 expression (p < 0.05), and enhanced TUNEL positivity (higher apoptosis, p < 0.01) in tumor cells as compared to other treatment groups, suggesting the therapeutic efficacy of the DDS. Altogether, the present study suggests that the DDS PTX-CUR-NPs could be employed for the effective treatment of breast cancers in near future.

Curcumin nanoparticles incorporated in PVA/collagen composite films promote wound healing.

Skin repair remains a common problem in plastic surgery. Wound dressing plays an important role in promoting local skin healing and has been widely studied. This study aimed to manufacture a composite film (CPCF) containing curcumin nanoparticles, collagen, and polyvinyl alcohol (PVA) to effectively promote the healing of skin wounds. Sustained drug release from the composite film provides long-term protection and treatment for skin wounds. Both antibacterial property and good histocompatibility of the CPCF were examined by analyzing antibacterial activity and cytotoxicity to validate its applicability for wound management. Moreover, in vivo studies proved that the CPCF had a rapid healing rate of 98.03%±0.79% and mature epithelialization on day 15 after surgery. Obvious hair follicles and earlier re-epithelialization was also noticed in the CPCF group using H&E staining. The result of Masson's trichrome staining confirmed that CPCF could promote the formation of collagen fibers. In summary, CPCF may be promising as a wound dressing agent in wound management owing to its rapid wound-healing effects.

Injectable Hyaluronic Acid Hydrogel for the Co-Delivery of Gemcitabine Nanoparticles and Cisplatin for Malignant Ascites Therapy.

Malignant ascites indicate the presence of malignant cells in the peritoneal cavity that lower patient survival and reduce quality of life. Current chemotherapy regimens suffer from the dilution of ascites and rapid metabolism limiting their therapeutic efficacy. The storage and sustained release of drugs at the tumor site represents a promising strategy to improve drug efficacy. The aim of this study was to develop injectable hyaluronic acid hydrogel containing polymeric gemcitabine nanoparticles and cisplatin for the local treatment of malignant ascites through a dual sustained drug release pattern. Cell uptake assays showed that the drug-loaded nanoparticles readily entered tumor cells. Apoptosis and cell cycle analysis showed that the hydrogel system could enhance tumor cell apoptosis and arrest more cells in the G1 phase. In vivo experiments indicated that mice treated with the drug-loaded hydrogels manifested the most significant efficacy in ascites volume, tumor nodules, body weight, abdominal circumference, and survival. The expression of Ki-67 and CD31 also significantly decreased compared with other groups, indicative of anti-tumor activity. In addition, intraperitoneal administration of the hydrogel system led to no significant damage to vital organs. These findings confirm the clinical potential of the drug-loaded hydrogel system for the treatment of malignant ascites.

Intraperitoneal administration of biocompatible hyaluronic acid hydrogel containing multi-chemotherapeutic agents for treatment of colorectal peritoneal carcinomatosis.

Colorectal peritoneal carcinomatosis (CRPC) is an advanced stage of colorectal cancer (CRC), which significantly decreases patient survival and quality of life. Here, the naturally occurring polysaccharide hyaluronic acid (HA) was used to prepare an injectable hydrogel and simultaneously deliver 5-fluorouracil (5-FU), cisplatin (DDP) and paclitaxel (PTX) microspheres for intraperitoneal CRPC chemotherapy. The drug-loaded HA hydrogel released the drugs in a sustained manner, and showed low toxicity both in vitro and in a mouse model of CRPC. Furthermore, direct injection of the drug-loaded HA hydrogel in the abdominal cavity of tumor-bearing mice significantly decreased tumor growth and liver/lung metastasis, along with decreasing the volume of ascites and inhibiting local intestinal infiltration of the tumor cells. Therefore, this novel multi-drug hydrogel delivery system may effectively clear CRPC tumors without any adverse effects when used in intraperitoneal chemotherapy.

Identification of Circulating MicroRNAs as a Promising Diagnostic Biomarker for Cervical Intraepithelial Neoplasia and Early Cancer: A Meta-Analysis.

BACKGROUND: Cervical cancer (CC) is one of the most common female malignant tumors. And cervical intraepithelial neoplasia (CIN) is the precancerous lesion of CC, which can progress to invasive CC. MicroRNAs (miRNAs) have been found to be potential diagnostic biomarkers for CIN or CC. However, recently, the lack of sufficient studies about the diagnostic value of miRNAs for CIN made it challenging to separately investigate the diagnostic efficacy of miRNAs for CIN. Likewise, the conclusions among those studies were discordant. Therefore, we conducted this meta-analysis, aimed at evaluating the diagnostic efficacy of miRNAs for CIN and CC patients. METHODS: Literature search was performed in PubMed, Embase, and Web of Science databases. Pooled sensitivity, specificity, and other diagnostic parameters were calculated through Stata 14.0 software. Furthermore, subgroup analyses and metaregression analysis were conducted to explore the main sources of heterogeneity. RESULTS: Ten articles covering 50 studies were eligible, which included 5,908 patients and 4,819 healthy individuals. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.81 (95% CI, 0.77-0.85), 0.86 (95% CI, 0.83-0.89), 5.9 (95% CI, 4.5-7.7), 0.22 (95% CI, 0.17-0.28), 27 (95% CI, 17-44), and 0.91 (95% CI, 0.88-0.93), respectively. Additionally, the ethnicity and internal reference were the main sources of heterogeneity. CONCLUSIONS: Circulating miRNAs can be a promising noninvasive diagnostic biomarker for CIN and early CC, especially miR-9 and miR-205, which need to be verified by large-scale studies.

Self-assembled dihydroartemisinin nanoparticles as a platform for cervical cancer chemotherapy.

Dihydroartemisinin (DHA) is a potent anti-cancer drug that has limited clinical applications due to poor water solubility and low bioavailability. We designed a biodegradable poly(ethylene glycol) methyl ether-poly(ε-caprolactone) (MPEG-PCL) micelle carrier for DHA using the self-assembly method. The DHA/MPEG-PCL nanoparticles were spherical with an average particle size of 30.28 ± 0.27 nm, and released the drug in a sustained manner in aqueous solution. The drug-loaded nanoparticles showed dose-dependent toxicity in HeLa cells by inducing cycle arrest and apoptosis. Furthermore, compared to free DHA, the DHA/MPEG-PCL nanoparticles showed higher therapeutic efficacy and lower toxicity in vivo, and significantly inhibited tumor growth and prolonged the survival of tumor-bearing nude mice. In addition, the tumor tissues of the DHA/MPEG-PCL-treated mice showed a marked decline in the in situ expression of proliferation and angiogenesis markers. Taken together, the self-assembled DHA/MPEG-PCL nanoparticles are a highly promising delivery system for targeted cancer treatment.

Controllable Synthesis of Co@CoOx/Helical Nitrogen-Doped Carbon Nanotubes toward Oxygen Reduction Reaction as Binder-free Cathodes for Al-Air Batteries.

Efficient and stable electrocatalysts for oxygen reduction reaction and freestanding electrode structure were developed to reduce the use of polymer binders in the cathode of metal-air batteries. Considering the unique geometrical configurations of helical carbon nanotubes (CNTs) and improved properties compared with straight CNTs, we prepared high-purity Co@CoOx/helical nitrogen-doped carbon nanotubes (Co@CoOx/HNCNTs) on a carbon fiber paper by hydrothermal and single-step in situ chemical vapor deposition strategies. Under an optimized growth time (1 h), the synthesized Co@CoOx/HNCNTs provide richer edge defects and active sites and show prominent electrocatalytic performance toward oxygen reduction reaction (ORR) under alkaline media compared with Co@CoOx/HNCNTs-0.5 h and Co@CoOx/HNCNTs-2 h. The soft X-ray absorption spectroscopy technique is used to investigate the influences of different growth times on the electronic structure and local chemical configuration of Co@CoOx/HNCNTs. Furthermore, the Al-air coin cell employing Co@CoOx/HNCNTs-1 h as the binder-free cathode exhibits an open-circuit voltage of 1.48 V, a specific capacity of 367.31 mA h g-1 at the discharge current density of 1.0 mA cm-2, and a maximum power density (Pmax) of 3.86 mW cm-2, which are superior to those of Co@CoOx/HNCNTs-0.5 h and Co@CoOx/HNCNTs-2 h electrodes. This work provides valuable insights into the development of scalable binder-free cathodes, exploiting HNCNT composite materials with an outstanding electrocatalytic performance for ORR in Al-air systems.

Variable-Energy Hard X-ray Photoemission Spectroscopy: A Nondestructive Tool to Analyze the Cathode-Solid-State Electrolyte Interface.

All-solid-state batteries are expected to be promising next-generation energy storage systems with increased energy density compared to the state-of-the-art Li-ion batteries. Nonetheless, the electrochemical performances of the all-solid-state batteries are currently limited by the high interfacial resistance between active electrode materials and solid-state electrolytes. In particular, elemental interdiffusion and the formation of interlayers with low ionic conductivity are known to restrict the battery performance. Herein, we apply a nondestructive variable-energy hard X-ray photoemission spectroscopy to detect the elemental chemical states at the interface between the cathode and the solid-state electrolyte, in comparison to the widely used angle-resolved (variable-angle) X-ray photoemission spectroscopy/X-ray absorption spectroscopy methods. The accuracy of variable-energy hard X-ray photoemission spectroscopy is also verified with a focused ion beam and high-resolution transmission electron microscopy. We also show the significant suppression of interdiffusion by building an artificial layer via atomic layer deposition at this interface.

Nanomechanical elasticity and fracture studies of lithium phosphate (LPO) and lithium tantalate (LTO) solid-state electrolytes.

All-solid-state batteries (ASSBs) have attracted much attention due to their enhanced energy density and safety as compared to traditional liquid-based batteries. However, cyclic performance depreciates due to microcrack formation and propagation at the interface of the solid-state electrolytes (SSEs) and electrodes. Herein, we studied the elastic and fracture behavior of atomic layer deposition (ALD) synthesized glassy lithium phosphate (LPO) and lithium tantalate (LTO) thin films as promising candidates for SSEs. The mechanical behavior of ALD prepared SSE thin films with a thickness range of 5 nm to 30 nm over suspended single-layer graphene was studied using an atomic force microscope (AFM) film deflection technique. Scanning transmission electron microscopy (STEM) coupled with AFM was used for microstructural analysis. LTO films exhibited higher stiffness and higher fracture forces as compared to LPO films. Fracture in LTO films occurred directly under the indenter in a brittle fashion, while LPO films failed by a more complex fracture mechanism including significant plastic deformation prior to the onset of complete fracture. The results and methodology described in this work open a new window to identify the potential influence of SSEs mechanical performance on their operation in flexible ASSBs.

Naproxen Nanoparticle-Loaded Thermosensitive Chitosan Hydrogel for Prevention of Postoperative Adhesions.

Postoperative adhesions are the most common complications of peri-abdominal surgery; they not only affect the patient's quality of life but also increase the risk of a subsequent surgery. The use of implantable dressings to physically block surgical wounds is the primary solution to prevent postoperative adhesions. In this study, we prepared naproxen nanoparticles that were loaded with chitosan hydrogel (CS/Nap hydrogel) to prevent postoperative adhesions. Our data confirmed that the prepared CS/Nap hydrogel was thermosensitive and suitable for injection. The efficacy of anti-adhesion in a rat model revealed that the hydrogel effectively separated from the wounds of the abdominal wall and cecum. On day 7 postsurgery, the wounds were completely covered by a new epithelial layer, whereas wounds in the negative control group were glued together. Additionally, the in vivo toxicity study showed that the CS/Nap hydrogel had fewer toxic and side effects on major tissues and organs, including the liver, spleen, heart, lung, and kidney. We showed that a drug delivery system based on CS/Nap hydrogel has the potential not only to prevent postoperative abdominal adhesions and relieve pain but also to contribute to the administration of the hydrophobic drug naproxen.