Assessment of the efficacy and safety of carbon nanoparticles-guided lymph node dissection in gastric cancer surgery: a systematic review and meta-analysis.

BACKGROUND: To investigate the efficacy and safety of lymph nodes (LNs) dissection guided by carbon nanoparticles (CNs) in gastric cancer (GC) surgery. MATERIALS AND METHODS: We searched electronic databases such as PubMed, Web of Science, Embase, Cochrane Library, and Scopus for relevant articles up to September 2022 and collected all studies comparing the CNs group with blank controls group on the efficacy and safety of LN dissection in gastrectomy. A pooled analysis of the collected data was performed, including the number of retrieved LNs, the staining rate of LNs, the number of metastatic LNs dissection, various intraoperative outcomes, and postoperative complications. RESULTS: A total of 9 studies including 1770 participants (502 in the CNs group and 1268 in the control group) were included. As compared to the blank control group, the CNs group detected 10.46 more LNs in each patient (WMD = 10.46, 95% CI: 6.63 ~ 14.28, p < 0.00001, I2 = 91%), and also significantly more metastatic LNs (WMD = 2.63, 95% CI: 1.43 ~ 3.83, p < 0.0001, I2 = 41%). However, there was no significant difference in the rate of metastatic LNs between the CNs and control groups (OR = 1.37, 95% CI: 0.94 ~ 2.00, P = 0.1, I2 = 89%). In addition, there was no increase in operative time, intraoperative blood loss, and postoperative complications associated with CNs-guided gastrectomy. CONCLUSION: CNs-guided gastrectomy is safe and effective, and can increase the efficiency of LN dissection without increasing the risk of surgery.

Safety and efficiency of sewage sludge and garden waste compost as a soil amendment based on the field application in woodland.

Sewage sludge (SS) and garden waste (GW) compost can be used as soil amendments to improve the soil environment. Studies done till date have been focused on the changes of harmful substances during sludge composting, but the safety and efficacy of SS and GW composting on woodland soil environment are still unclear. In the study, a field experiment was performed using to investigate the safety and efficacy of SS and GW compost as a soil amendment on woodland soil. Soil nutrients (such as nitrogen, phosphorus and potassium), organic matter and electrical conductivity were significantly increased after the addition of the SS and GW compost, while there were no significant changes in soil heavy metals content and soil enzyme activities. From these soil properties, it was found that SS and GW compost was safe and efficacious in improving the soil environment. The application of SS and GW compost had no significant effect on microbial diversity. Co-occurrence network analysis revealed that SS and GW compost efficaciously enhanced the interaction between bacterial communities, which proved that it was safe and efficacious. Furthermore, SS and GW compost enhanced ABC transporters and carbohydrate metabolism of bacterial community, while reduced the pathotroph action (such as the plant pathogen) and wood saprotrophs. Overall, these results proved the safety and efficacy of SS and GW compost as soil amendments after being added to the soil. This study contributes to the use of harmless treatments and reutilization processes of SS and GW.

Investigation on the Component Evolution of a Tetranuclear Nickel-Cluster-Based Metal-Organic Framework in an Electrochemical Oxidation Reaction.

Understanding the active species derived from metal-organic frameworks (MOFs) plays a vital role in the fabrication of highly efficient and stable oxygen evolution reaction (OER) electrocatalysts. Herein, a new alkaline-stable 3D nickel metal-organic framework (Ni-MOF), containing a 1D rod-packing chain structure fused with a tetranuclear nickel cluster [Ni4(µ3-OH)2], is used as a target material to explore its OER properties. The electrocatalytic activities of pure Ni-MOF and hybrid materials made from Ni-MOF with different acetylene black loaded electrodes, such as glassy carbon, fluorine-doped tin oxide, and nickel foam, have been evaluated. Further analysis unravels that the enhanced OER performance might be attributed to the synergistic interactions of two catalytic active species between in situ formed ß-Ni(OH)2 and a tetranuclear Ni4(µ3-OH)2 cluster in Ni-MOF. The findings will shed fresh light on the fabrication of MOF-derived catalysts for efficient electrochemical energy conversion.

Reduction-responsive sulfur dioxide polymer prodrug nanoparticles loaded with irinotecan for combination osteosarcoma therapy.

Combination therapy can boost the therapeutic effectiveness of monotherapies by achieving synergy between therapeutic agents. Herein, a reduction-responsive sulfur dioxide (SO2) polymer prodrug was synthesized as a nanocarrier to load irinotecan (IRN) to be used in combination osteosarcoma therapy. The SO2 prodrug (denoted as mPEG-PLG (DNs)) was synthesized by coupling a small-molecule SO2 donor, N-(3-azidopropyl)-2,4-dinitrobenzenesulfonamide (AP-DNs), to the side chains of methoxy poly (ethylene glycol)-block-poly (γ-propargyl-L-glutamate) block copolymer. The mPEG-PLG (DNs) had the ability to self-assemble into micelles while simultaneously encapsulating IRN in aqueous media. The formed micelles led to enhanced SO2 and IRN release in reductive conditions. Using nile red as a model drug, the loaded micelles were efficiently internalized by cancer cells, demonstrated by confocal laser scanning microscopy and flow cytometry. The release of SO2 within nanoparticles (NPs) in tumor cells led to enhanced intracellular reactive oxygen species amounts together with induced oxidative destruction to cancer cells. Furthermore, the IRN-loaded SO2 polymer prodrug NPs mediated synergistic therapeutic effects against osteosarcoma cells, leading to improved biodistribution and enhanced tumor growth inhibition over control groups in a murine osteosarcoma model. Taken together, this work highlights the potential of SO2 polymer prodrugs as reduction-responsive nanocarriers to load chemotherapeutics for effective combination osteosarcoma therapy.

Integration of Semiconductor Oxide and a Microporous (3,10)-Connected Co6-Based Metal-Organic Framework for Enhanced Oxygen Evolution Reaction.

Developing high-efficiency and cost-effective electrocatalytic oxygen evolution reaction (OER) catalysts would determine the future distributions of energy conversion technologies. Metal-organic frameworks (MOFs), with unsaturated active metal sites, functionalized organic linkers, and large surface areas, are emerging heterogeneous electrocatalysts for the water oxidation process. Herein, we report an oxygen-evolving microporous (3,10)-connected Co6-based MOF (denoted as CTGU-14) for the electrocatalytic OER. Moreover, the integration of Co-MOF and SnO2, SnO2 (15%) & CTGU-14 composite attains remarkable electrochemical OER performance with a small Tafel slope of 68 mV·dec-1, a positive overpotential of 388 mV at 10 mA·cm-2, and overall durability in an alkali medium. The superior OER activities might be ascribed to more convenient electron transfer from the SnO2 additive to the electrode medium, effective surface area and unsaturated active cobalt centers, and more beneficial delivery for hydroxy radicals in the microporous Co-MOF skeleton in the process of the OER.

Up-regulation of CRKL by microRNA-335 methylation is associated with poor prognosis in gastric cancer.

BACKGROUND: MicroRNAs have been suggested to play a vital role in regulating carcinogenesis, tumor progression and invasion. MiR-335 is involved in suppressing metastasis and invasion in various human cancers. However, the mechanisms responsible for the aberrant expression of miR-335 in gastric cancer (GC) remain unknown. METHODS: Expression of miR-335 in four GC cell lines and 231 GC tissues was determined by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). DNA methylation status in the CpG islands upstream of miR-335 in GC cell lines and tissues was determined by methylation-specific PCR and bisulfite sequence-PCR. The effects of the demethylating agent 5-aza-2'-deoxycytidine on cell proliferation, apoptosis, cell cycle, migration, and invasion were investigated in GC cell lines. RESULTS: Cancer-specific methylation was detected in the upstream CpG-rich regions of miR-335, which dramatically silenced its transcriptional activity in GC cell lines and tissues. Low levels of miR-335 expression and high levels of miR-335 methylation in GC tissues were associated with poor clinical features and prognosis. Restoration of miR-335 expression in GC cells promoted cell apoptosis, inhibited tumor cell migration, invasion, and proliferation, and arrested the cell cycle at G0/G1 phase. Overexpression of miR-335 significantly reduced the activity of a luciferase reporter containing the 3' untranslated region of V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL). CONCLUSIONS: MiR-335 functions as a tumor suppressor and may be silenced by promoter hypermethylation. It plays a role in inhibiting tumor cell migration, invasion, and proliferation, arresting the cell cycle at G0/G1 phase, and promoting apoptosis in GC cells through targeting CRKL.

Role of RASSF1A promoter methylation in the pathogenesis of hepatocellular carcinoma: a meta-analysis of 21 cohort studies.

We carried out the current meta-analysis aiming to comprehensively assess the potential role of RASSF1A aberrant promoter methylation in the pathogenesis of hepatocellular carcinoma (HCC). A range of electronic databases were searched: Web of Science (1945-2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966-2013), EMBASE (1980-2013), CINAHL (1982-2013) and the Chinese Biomedical Database (CBM) (1982-2013) without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude risk difference (RD) with their 95% confidence interval (95% CI) was calculated. In the present meta-analysis, 21 clinical cohort studies with a total of 1,205 HCC patients were included. The results of our meta-analysis illustrated that the frequency of RASSF1A promoter methylation in cancer tissues were significantly higher than those of normal, adjacent and benign tissues (cancer tissues vs. normal tissues: RD = 0.63, 95% CI 0.53-0.73, P < 0.001; cancer tissues vs. adjacent tissues: RD = 0.43, 95% CI 0.33-0.53, P < 0.001; cancer tissues vs. benign tissues: RD = 0.48, 95% CI 038-0.58, P < 0.001; respectively). Further subgroup by ethnicity demonstrated that RASSF1A aberrant promoter methylation was correlated with the pathogenesis of HCC among both Asians and Caucasians (all P < 0.05). The current meta-analysis suggests that RASSF1A aberrant promoter methylation may be implicated in the pathogenesis of HCC. Thus, detection of RASSF1A promoter methylation may be a helpful and valuable biomarker for diagnosis and prognosis of HCC.

The biological role of extracellular vesicles in gastric cancer metastasis.

Gastric cancer (GC) is a tumor characterized by high incidence and mortality, with metastasis being the primary cause of poor prognosis. Extracellular vesicles (EVs) are an important intercellular communication medium. They contain bioactive substances such as proteins, nucleic acids, and lipids. EVs play a crucial biological role in the process of GC metastasis. Through mechanisms such as remodeling the tumor microenvironment (TME), immune suppression, promoting angiogenesis, and facilitating epithelial-mesenchymal transition (EMT) and mesothelial-mesenchymal transition (MMT), EVs promote invasion and metastasis in GC. Further exploration of the biological roles of EVs will contribute to our understanding of the mechanisms underlying GC metastasis and may provide novel targets and strategies for the diagnosis and treatment of GC. In this review, we summarize the mechanisms by which EVs influence GC metastasis from four aspects: remodeling the TME, modulating the immune system, influencing angiogenesis, and modulating the processes of EMT and MMT. Finally, we briefly summarized the organotropism of GC metastasis as well as the potential and limitations of EVs in GC.

High-performance sono-piezoelectric nanocomposites enhanced by interfacial coupling effects for implantable nanogenerators and actuators.

Transcutaneous energy-harvesting technology based on ultrasound-driven piezoelectric nanogenerators is the most promising technology in medical and industrial applications. Based on ultrasonic coupling effects at the interfaces, the interfacial architecture is a critical parameter to attain desirable electromechanical properties of nanocomposites. Herein, we successfully synthesized core-conductive shell-structured BaTiO3@Carbon [BT@Carbon] nanoparticles [NPs] as nanofillers to design implantable poly(vinylidenefluoride-co-chlorotrifluoroethylene)/BT@Carbon [P(VDF-CTFE)/BT@Carbon] piezoelectric nanogenerators (PENGs) and actuators for harvesting ultrasound (US) underneath the skin. For US-driven PENGs, the electrons and holes are generated not only from the interfaces between the BT@Carbon NPs and the matrix, but also from the dipoles vibrating in the smaller lamellae of ferroelectric ß-phase crystals in poled nanocomposites. Remarkably, P(VDF-CTFE)/BT@Carbon piezoelectric nanogenerators could attain an extraordinary output power of 521 µW cm-2 under ultrasound stimulation, which is far greater than that of force-induced PVDF-based nanogenerators and other ultrasound-driven triboelectric generators. Furthermore, the US-PENG actuator system, which is composed of an amplifier and a microcontroller, could efficiently convert ultrasonic energy into electricity or instructions to switch on/off small electronics in the tissues and organs of mice. Finally, the nanocomposite-based US-driven PENGs have a good biocompatibility, with no cytotoxicity or immune response in vivo, indicating their potential for developing wireless power generators and actuators for medical implant devices.

MiR-5195-3p targets the PCBP2/PI3K/AKT pathway to inhibit melanoma cell proliferation and migration.

Although miR-5195-3p has been acknowledged for its tumor suppressor role in diverse cancer categories, its precise functions and mechanisms concerning melanoma have not been comprehensively elucidated. In this study, we employed quantitative reverse transcription PCR, Western blot analysis, and immunohistochemistry staining to investigate the expression patterns of miR-5195-3p and poly (rC) binding protein 2 (PCBP2) in melanoma tissues compared to adjacent tissues. Our findings revealed downregulation of miR-5195-3p and upregulation of PCBP2 in melanoma tissues. Through the implementation of a luciferase reporter assay, we successfully identified PCBP2 as a newly discovered target of miR-5195-3p in melanoma cells. Enforced expression of miR-5195-3p via mimics inhibited cell proliferation and migration in A375 and A2058 cells, as demonstrated by CCK-8 and transwell migration assays. In melanoma cells, reintroduction of PCBP2 partially reversed the inhibitory effects of miR-5195-3p overexpression. Treatment with LY294002, an inhibitor of the PI3K/AKT signaling pathway, also reversed the effects of PCBP2 in melanoma cells. Furthermore, our results suggest that miR-5195-3p inhibits the activation of the PI3K/AKT signaling pathway in melanoma by inhibiting PCBP2. In conclusion, our research has identified the miR-5195-3p targeting of the PCBP2-mediated PI3K/AKT signaling pathway as a potential therapeutic target for melanoma treatment.

Electron-beam writing of a relaxor ferroelectric polymer for multiplexing information storage and encryption.

To meet the strong demand for high-level encryption security, several efforts have been focused on developing new encryption techniques with high density and data security. Herein we employed a template-free electron beam lithography (EBL) technique to write various nanopatterns on poly(vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) (P(VDF-TrFE-CTFE)) films and applied it to electron-beam/electric multiplexing memory. Furthermore, electron beams can arbitrarily tailor down the domain structure evolutions and dipole directions, as proved by a combination of AFM-IR and PFM. Finally, our devices could function concurrently as an electron-beam write-only-memory (EB-WOM) and FeRAM, where the information could be encoded with the metastable phase evolutions from the ferroelectric phase to the paraelectric phase and variable bi-level ferroelectric signals. Our systematic study provides an inspiring idea for the design of information encryption devices with high-security requirements in flexible electronic fields.

Sequelae of long COVID, known and unknown: A review of updated information.

Over three years have passed since the COVID-19 pandemic started. The dangerousness and impact of COVID-19 should definitely not be ignored or underestimated. Other than the symptoms of acute infection, the long-term symptoms associated with SARS-CoV-2 infection, which are referred to here as "sequelae of long COVID (LC)", are also a conspicuous global public health concern. Although such sequelae were well-documented, the understanding of and insights regarding LC-related sequelae remain inadequate due to the limitations of previous studies (the follow-up, methodological flaws, heterogeneity among studies, etc.). Notably, robust evidence regarding diagnosis and treatment of certain LC sequelae remain insufficient and has been a stumbling block to better management of these patients. This awkward situation motivated us to conduct this review. Here, we comprehensively reviewed the updated information, particularly focusing on clinical issues. We attempt to provide the latest information regarding LC-related sequelae by systematically reviewing the involvement of main organ systems. We also propose paths for future exploration based on available knowledge and the authors' clinical experience. We believe that these take-home messages will be helpful to gain insights into LC and ultimately benefit clinical practice in treating LC-related sequelae.

Correction to "MicroRNA-320a suppresses tumor progression by targeting PBX3 in gastric cancer and is downregulated by DNA methylation".

[This corrects the article on p. 842 in vol. 11, PMID: 31662823.].

Risk Factors for Actinic Keratoses: A Systematic Review and Meta-Analysis.

Objective: To integrate evidence and assess the risk factors associated with actinic keratosis (AK). Methods: Unrestricted searches were conducted on five electronic databases, with an end-date parameter of September 2021. We summarized the study characteristics and pooled the results from individual studies by using a random-effects model. The risk of bias was estimated using the Cochrane Risk of Bias Tool, and the quality of evidence was estimated according to the Newcastle-Ottawa Scale. Results: Sixteen studies were included in final analysis, and we assessed the AK risk among a variety of risk factors. Overall, the male sex (odds ratio (OR): 2.51; 95% confidence interval (CI): 1.94-3.25; P < 0.01), age >45 years (OR = 7.65, 95% CI: 2.95-19.86; P < 0.01), light Fitzpatrick skin phototype (OR = 2.32, 95% CI: 1.74-3.10; P < 0.01), light hair color (OR = 2.17, 95% CI: 1.40-3.36; P < 0.01), light eye color (OR = 1.67, 95% CI: 1.03-2.70; P = 0.04), freckles on face/arms (OR = 1.88, 95% CI: 1.37-2.58; P < 0.01), suffered positive history of other types of non-melanoma skin cancer (OR = 4.46, 95% CI: 2.71-7.33; P < 0.01), sunburns in childhood (OR = 2.33, 95% CI: 1.47-3.70; P < 0.01) and adulthood (OR = 1.50, 95% CI: 1.12-2.00; P < 0.01), severe sunburn (OR = 1.94, 95% CI: 1.62-2.31; P < 0.01), and chronic occupational and/or recreational sun exposure (OR = 3.22, 95% CI: 2.16-4.81; P < 0.01) increased the risk of AK. Moreover, sunscreen use (OR = 0.51, 95% CI: 0.34-0.77; P < 0.01) and history of atopy reduced the risk of AK. Sensitivity analysis yielded consistent results. The included studies showed a high risk of bias. Conclusion: We confirm several well-known AK risk factors and their quantitative data, and summarized the uncommon risk factors and protective factors. Our results may inform on the design and implementation of AK screening and educational programs.

Molecular characterization of the composition and transformation of dissolved organic matter during the semi-permeable membrane covered hyperthermophilic composting.

Current knowledge of dissolved organic matter (DOM) in semi-permeable membrane-covered thermophilic compost (smHTC) is limited. Therefore, this study provided a comprehensive characterization of composition and transformation of DOM in smHTC using multiple spectroscopic methods and ultrahigh resolution mass spectrometry. The results showed that the values of SUVA280, SUVA254, A240-400 (0.042, 0.048, 34.193) in smHTC were higher than those of conventional thermophilic composting (cTC) (0.030, 0.037, 18.348), and the increment of PV,n in smHTC were 2.4 times higher than that of cTC. These results suggested that smHTC accelerated the humification process by promoting the degradation of labile DOM and the production of humus-like substances. Mass spectrometry further confirmed that the DOM of smHTC possessed higher degree of aromatization and humification, based on the lower H/C (1.14), higher aromaticity index (0.34) and double bond equivalence (10.36). Additionally, smHTC increased the proportion of carboxyl-rich, unsaturated and aromatic compounds, and simultaneously improved the degradation of aliphatic/proteins, lipids, carbohydrates, along with even some refractory substances such as CHO subcategory (24.1%), especially lignin-like structures (14.8%). This investigation provided molecular insights into the composition and transformations of DOM in smHTC, and extended the current molecular mechanisms of humification in composting.

Nanocarriers for intracellular co-delivery of proteins and small-molecule drugs for cancer therapy.

In the past few decades, the combination of proteins and small-molecule drugs has made tremendous progress in cancer treatment, but it is still not satisfactory. Because there are great differences in molecular weight, water solubility, stability, pharmacokinetics, biodistribution, and the ways of release and action between macromolecular proteins and small-molecule drugs. To improve the efficacy and safety of tumor treatment, people are committed to developing protein and drug co-delivery systems. Currently, intracellular co-delivery systems have been developed that integrate proteins and small-molecule drugs into one nanocarrier via various loading strategies. These systems significantly improve the blood stability, half-life, and biodistribution of proteins and small-molecule drugs, thus increasing their concentration in tumors. Furthermore, proteins and small-molecule drugs within these systems can be specifically targeted to tumor cells, and are released to perform functions after entering tumor cells simultaneously, resulting in improved effectiveness and safety of tumor treatment. This review summarizes the latest progress in protein and small-molecule drug intracellular co-delivery systems, with emphasis on the composition of nanocarriers, as well as on the loading methods of proteins and small-molecule drugs that play a role in cells into the systems, which have not been summarized by others so far.

[Effects of Nano-membrane on Aerobic Composting Process and Odor Emission of Livestock Manure].

Aerobic composting is an important approach to treat livestock manure; however, traditional composting has some problems, such as low efficiency, or odorous pollution. In order to speed up the composting process and reduce malodorous gas emissions, this study explored the mechanism of nano-membrane for improving the efficiency of livestock manure composting. A trough aerobic composting experiment was set up to evaluate the physicochemical properties, enzyme activities, and emission of odorous gases. The results showed that covering with nano-membrane could accelerate the temperature rise; reduce the pH, organic matter(OM), and ammonia nitrogen(NH4+-N); increase electrical conductivity(EC); enhance the activities of urease, protease, cellulase, xylanase, and peroxidase; while the total cumulative emissions of NH3, H2S, and TVOC were reduced by 58%, 100%, and 61%, respectively. The correlation analysis showed that most enzyme activities were easily affected by temperature(T), EC, OM, and C/N. The emission rate of NH3 was positively correlated with T and negatively correlated with pH, and TVOC was significantly correlated with various physicochemical properties. This experiment showed that covering nano-membrane could accelerate the compost maturity and reduce the emission of odorous gases. This approach has no health risks and produces low malodorous gas, which may effectively solve the problem of pollutant emission caused by livestock manure compost fermentation, promoting the green and sustainable development of the breeding industry. In addition, it facilitates livestock manure fertilizer application, and provides technical support for the development of resource utilization of biomass waste.

Common Strategy: Mounting the Rod-like Ni-Based MOF on Hydrangea-Shaped Nickel Hydroxide for Superior Electrocatalytic Methanol Oxidation Reaction.

Developing efficient metal-organic framework (MOF)-based electrocatalysts with improvable activity and persistence toward the methanol oxidation reaction (MOR) is attracting great research attention but still remains an enormous challenge. Herein, a facile strategy, hydrangea-shaped nickel hydroxide template-directed synthesis of the hierarchically structured Ni-MOF on the Ni(OH)2 heterocomposite (denoted as Ni-Ni) for efficient MOR, is developed. The unique hierarchical structure and synergistic effect of the heterocomposite afford more exposed active sites, a facile ion diffusion path, and improved conductivity, favorable for improving MOR catalytic performance. Remarkably, the optimized Ni-Ni-2 material delivers an excellent activity with a high peak current density (24.6 mA cm-2). Furthermore, to prove the universality of this strategy, NixCu1-x(OH)2 isometallic hydroxide was used as the precursor, and a series of MOF-74/CuxNi1-x(OH)2 (denoted as Ni-NiCu) heterogeneous materials have been prepared and could be used as an effective electrocatalyst to catalyze MOR. The results indicate that this strategy can be used in the synthesis of other new composite materials with specific hierarchical structures for a more efficient electrocatalytic system.

Development of a Hyaluronic Acid-Based Nanocarrier Incorporating Doxorubicin and Cisplatin as a pH-Sensitive and CD44-Targeted Anti-Breast Cancer Drug Delivery System.

Tumor-targeting nanomaterial-based chemotherapeutic drug delivery systems have been shown to represent an efficacious approach for the treatment of cancer because of their stability in blood circulation and predictable delivery patterns, enhanced tumor-selective drug accumulation, and decreased toxicity to normal tissues. The cell-surface transmembrane glycoprotein CD44 binds to the extracellular domain of hyaluronic acid (HA), and is overexpressed in breast, ovarian, lung, and stomach cancer. In this study, an HA-based nano-carrier incorporating doxorubicin (DOX) and cisplatin (CDDP) was synthesized as a CD44-targeting anti-cancer drug delivery system, and its tumor inhibition effects against CD44+ breast cancer cells were evaluated in vitro and in vivo. These dual drug-loaded HA micelles (HA-DOX-CDDP) exhibited significantly enhanced drug release under acidic conditions, and showed higher cellular uptake and stronger cellular growth inhibition than free drugs against 4T1 (CD44+) breast cancer cells. In contrast, no significant differences in growth inhibition and cellular uptake were observed between HA-DOX-CDDP and free drugs in NIH-3T3 (CD44-) control cells. Furthermore, HA-DOX-CDDP micelles exhibited stronger inhibitory effects and lower systemic toxicity than free drugs in a 4T1 mammary cancer-bearing mouse model, as determined using immunofluorescence and histological analyses. Therefore, HA-DOX-CDDP micelles represent a promising drug delivery system that exhibits acid-sensitive drug release, CD44-targeted delivery, and excellent biocompatibility and biodegradation. These properties resulted in excellent tumor accumulation and reduced adverse effects, indicating that HA-DOX-CDDP micelles have promising potential applications in chemotherapy for breast cancer.

Co-delivery of doxorubicin and paclitaxel by reduction/pH dual responsive nanocarriers for osteosarcoma therapy.

Nanoparticle-based drug delivery system offers a promising platform for combination cancer therapy. However, the inefficient drug release in cells reduces the therapeutic efficacy of cancer nanomedicines. Herein, a PEGylated poly(α-lipoic acid) copolymer (mPEG-PαLA) was prepared and used as a reduction/pH dual responsive nanocarrier to simultaneously deliver paclitaxel (PTX) and doxorubicin (DOX) for osteosarcoma therapy. The amphiphilic mPEG-PαLA could efficiently encapsulate both PTX and DOX during its self-assembly into micelles in aqueous solution to generate PTX and DOX co-loaded nanoparticles (NP-PTX-DOX). The as-prepared NP-PTX-DOX showed enhanced PTX and DOX release in response to reductive and acidic stimuli. Moreover, the dual-drug loaded nanoparticles were efficiently internalized by K7 osteosarcoma cells and released drugs intracellularly, as confirmed by flow cytometry analysis and confocal laser scanning microscopy. Consequently, NP-PTX-DOX exhibited synergistic therapeutic effects and induced enhanced cell apoptosis in K7 cells. Furthermore, NP-PTX-DOX presented improved biodistribution and higher tumor growth inhibition efficacy compared to the control groups in a murine osteosarcoma model. Altogether, the results of this work indicate that the proposed strategy is promising for osteosarcoma therapy using mPEG-PαLA copolymer as a dual-responsive nanocarrier to co-deliver anticancer drugs.