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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

A point-of-care testing biosensing platform integrated with physiologically based pharmacokinetic model for on-site therapeutic drug monitoring of methotrexate

Feng-Feng Zhang,Mei-Juan Wu,Zi-Wei Yu,Yi-Lan Lin,Pin-Fang Huang,Meng-Meng Liu

Methotrexate (MTX) has definite dose-response relationship, in which high level MTX in serum leads to severe adverse events such as hepatotoxicity and myelosuppression. Therapeutic drug monitoring (TDM) of MTX helps to improve clinical outcomes and reduce toxic side effects. Nevertheless, standard methods are restricted by time-consumption, high cost and multiple repetitive sampling. Herein, a point-of-care testing (POCT) sensor was integrated with physiologically based pharmacokinetic (PBPK) model for on-site TDM of MTX to obtain patient-specific concentration-time ( C-T ) profiles, guiding leucovorin rescue and managing toxicities of high dose MTX. The sensor employed graphene oxide (GO)-ionic liquid (IL) modified screen-printed carbon electrodes in conjunction with a portable electrochemical workstation to achieve fast and accurate MTX detection in human serum via cyclic voltammetry, exhibiting two distinct linear dynamic ranges (0.1 nM-100 μM and 100 μM-3 mM) with a detection limit of 1.3 pM. The GO-IL composite enables selective MTX detection through different oxidation potentials, π-π stacking with MTX's pteridine ring, and charge/hydrophobicity-guided exclusion of interferents, achieving discrimination against key interferents including 7-OH MTX. Pearson correlation analysis and Bland-Altman consistency analysis demonstrated that MTX concentrations of 86 clinical samples measured by the sensor were consistent with that of immunoassay. Innovatively, PBPK model of MTX was developed to effectively process the complex MTX concentration data to obtain personalized C-T profiles of each patient. The individual PK parameters like maximum concentration and area under the curve can be easily acquired through C-T profiles, allowing for rapid clinical decision making. The MTX-PBPK model displayed reliable predictive accuracy of PK parameters within 2.0-fold-error. The results demonstrate that the POCT sensor combined with PBPK model is promising to be used for on-site TDM of MTX, promoting the development of individualized medication.

CAS / MDL: 59-30-3 60-27-5
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2025 · IF 5.6

Anisotropic Growth Method for Constructing Stimulus-Responsive Janus Composite Nanoparticles for Dual-Drug Delivery in Tumor Therapy

Yifan Peng,Xiaoqin Cai,Shanshan Wang,Kaikun Pi,Bin Sun,Yan Li,Bing Liu,Fangxiang Song

In this study, we used an interfacial energy-mediated, anisotropic growth method to synthesize rod-shaped, periodic mesoporous organosilica (PMO) on the surface of the mesoporous silicon-titanium composite nanoparticles (MSTNs) with a core-shell structure, resulting in sphere-rod structured, Janus composite nanoparticles (MSTNs/PMO). Adjusting the amount of surfactant and the solvent ratio (water/ethanol) in the reaction system allowed for the fabrication of MSTNs/PMO nanoparticles with diverse morphologies, and their growth mechanism was analyzed systematically. The MSTNs/PMO surface was functionalized with amino and thiol groups to facilitate the loading of doxorubicin (DOX) and tetrandrine (TET). Then, folic acid (FA) was grafted onto the drug-loaded nanoparticles (MSTNs/PMO-DOX/TET-FA). This step successfully constructed a stimulus-responsive combinatorial dual-drug delivery system. MSTNs/PMO-DOX/TET-FA exhibited high loading efficiencies, reaching 26.54% for DOX and 6.37% for TET. Drug release studies demonstrated significant pH-responsive release behavior and sequential release characteristics of the system. Cytotoxicity and cellular uptake assays revealed that the system exhibited excellent biosafety and significant targeting ability toward tumor cells. Collectively, these findings suggested that the dual-drug delivery system has potent antitumor therapeutic efficacy and offered a viable strategy for synergistic tumor therapy.

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COLLOIDS AND SURFACES B-BIOINTERFACES · 2024 · IF 5.4

Reactive oxygen species produced by photodynamic therapy enhance docosahexaenoic acid lipid peroxidation and induce the death of breast cancer cells

Weiwei Bai,Yongyong Xue,Yiyan Guo,Dandan Zhang,Kuo Ma,Zhendong Chen,Kunwen Xia,Beining Liao,Guowei Huang,Shengjun Pan,Yuxin Zheng,Haoyuan Wang,Hao Yang,Ling-Kun Zhang,Yan-Qing Guan

Breast cancer remains a serious threat to women's physical and emotional health. The combination therapies can overcome the deficiency of single therapy, enhance the therapeutic effects and reduce the side effects at the same time. In this study, we synthesize a novel nanomedicine that enhanced the therapeutic effects of breast cancer treatment by combining photodynamic therapy and chemotherapy. The doxorubicin (DOX) and photosensitizer methyl pyropheophorbide-a (MPPa) are loaded into the nano-drug delivery system as DPSPFA/MPPa/DOX. In response to near-infrared (NIR) laser, the drugs were quickly released to the cancer cells. The MPPa produces reactive oxygen species (ROS) under the action of photodynamics. Unsaturated fatty acids with ROS promotes lipid peroxidation and the combination of chemotherapy and photodynamic therapy. The data shows that the DPSPFA/MPPa/DOX has a spherical shape, good dispersibility and stability, and the particle size is roughly 200 nm. The drug loading capability of DOX is about 13 %. Both of MCF7 cell model in vitro and breast cancer model in vivo , DPSPFA/MPPa/DOX showed an excellent anti-tumor effect of 86.9 % and without any obvious side effects. These findings might offer potential for a new approach for breast cancer treatment.

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Bioresources and Bioprocessing · 2024 ·Vol. 11 ·期 1 ·1-12 · IF 4.3

Transcriptomics-guided optimization of vitamins to enhance erythromycin yield in saccharopolyspora erythraea

Ke Xiang,Jiang Xing,Wang Shuohan,Tian Xiwei,Chu Ju

Comparative transcriptomics uncovered distinct expression patterns of genes associated with cofactor and vitamin metabolism in the high-yielding mutant strain Saccharopolyspora erythraea HL3168 E3, as compared to the wild-type NRRL 2338. An in-depth analysis was conducted on the effects of nine vitamins, and it was determined that thiamine pyrophosphate (TPP), vitamin B2, vitamin B6, vitamin B9, vitamin B12, and hemin are key enhancers in erythromycin production in E3, increasing the erythromycin titer by 7.96–12.66%. Then, the Plackett-Burman design and the path of steepest ascent were applied to further optimize the vitamin combination for maximum production efficiency, enhancing the erythromycin titer in shake flasks by 39.2%. Otherwise, targeted metabolomics and metabolic flux analysis illuminated how vitamin supplementation modulates the central carbon metabolism with notable effects on the TCA cycle and methionine synthesis to augment the provision of energy and precursors essential for erythromycin synthesis. This work highlights the capacity for precise vitamin supplementation to refine metabolic pathways, thereby boosting erythromycin production, and provides valuable directions for application on an industrial scale. Graphical

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Acta Biomaterialia · 2025 · IF 9.6

A drug reservoir strategy for long-acting cancer therapy using morphologically transformed amphiphilic polymeric nanoparticles

Jiao Sun,Yiqing Wang,Jiaxing Zhang,Jianhao Wang,Cheng Wang

The effective accumulation of drugs within tumor tissues is impeded by extracellular barriers, necessitating repeated dosing in cancer therapy. However, repeated dosing can trigger the accelerated blood clearance (ABC) effect, resulting in limited therapeutic efficacy. Herein, in this study, a drug reservoir strategy was proposed to solve this dilemma, using an amphiphilic polymer (LPHF) with tunable hydrophilicity and morphology transformation capabilities. At pH 7.4, LPHF with balanced hydrophilicity can self-assemble into nanoparticles and be loaded with Dox (LPHF@Dox). At pH 6.5, LPHF@Dox with reduced hydrophilicity undergoes an immediate transition from a dispersed state to a deposited state, which can serve as a tumor-specific drug reservoir. Under the weakly acidic tumor microenvironment, the amide with adjacent carboxylic acid groups in LPHF exhibits pH-dependent hydrolysis, leading to a reversion of LPHF to a hydrophilic state and reconstitution into nanoparticles (LPHF@Dox RC ). The resulting LPHF@Dox RC undergoes charge reversal to a positive state, which coordinated with conjugated folic acid, to synergistically improves both the cellular internalization and tumor penetration of LPHF@Dox RC . This intelligent amphiphilic polymer, functioning as a tumor-specific drug reservoir, may provide a new approach for effective cancer treatment. Statement of significance This study introduces a pH-responsive polymeric nanoparticle (LPHF) that transforms into a tumor-specific drug reservoir under acidic conditions, addressing the challenge of repeated dosing in cancer therapy. Unlike conventional systems, LPHF deposits directly in tumors via pH-triggered hydrophobicity changes. As the tumor microenvironment hydrolyzes LPHF, it releases reconstituted nanoparticles with positive charges, enhancing cellular uptake and deep tumor penetration. This dual-phase strategy—localized drug retention followed by controlled release—significantly reduces side effects and improves therapeutic efficacy. By combining material innovation with biological insights, this work offers a promising approach for long-acting cancer treatment, potentially minimizing dosing frequency. Its interdisciplinary design bridges chemistry and biomedicine, appealing to researchers and students interested in smart drug delivery and sustainable healthcare solutions.

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JOURNAL OF POWER SOURCES · 2025 · IF 7.9

Ultra-long cycling stability of aqueous zinc-ion batteries via self-assembled folic acid forming protective interface layer at zinc anodes

Mingliang Li,Lu Tian,Xinning Huang,Jinxiao Dou,Jianglong Yu,Xingxing Chen

Aqueous zinc-ion batteries (AZIBs) are recognized as one of the most promising battery technologies, but dendrite growth and persistent parasitic reactions at the Zn anode hinder their practical use. This study employs cost-effective and source-abundant folic acid (FA) as a multifunctional electrolyte additive, which is self-assembled at the Zn anode, forming an effective layer improving the reversibility and stability of the zinc anode/electrolyte interface. In-situ Raman reveals the electrostatic shielding effect of the layer against SO 4 2− anions. In-situ scanning vibrating electrode technique (SVET) further verifies the superior inhibitory effect of the interface layer on Zn anode corrosion. Practically, Zn//Zn symmetric battery filled with ZnSO 4 /0.1 FA electrolyte achieves a prominent cycling stability of 9500 h at 0.2 mA cm −2 and 0.2 mAh cm −2 , and the constructed Zn//Cu half battery exhibits a high reversibility (99.69 %) after 1045 cycles. Strikingly, Zn//MnO 2 full battery also demonstrates outstanding charge/discharge durability for at least 900 cycles with a high reversibility of >99.94 % at 5 C. This study provides a novel paradigm for the development of environmentally benign and cost-efficient electrolyte, pivotal in realizing exceptionally reversible AZIBs.

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MICROCHEMICAL JOURNAL · 2025 · IF 5.1

Wearable biosensor with high specific surface area PGA-CNTs electrode for sweat glucose detection

Yuting Zheng,Yunfan Zhang,Zifan Xue,Hui Li,Shengnan Shen

Sweat glucose sensors have a high potential to detect blood glucose concentration conveniently and quickly, making them a focus of research on glucose detection methods. We prepare a polyglycolic acid-carbon nanotubes (PGA-CNTs) film with a high specific surface area, loaded with glucose oxidase (GOx) to develop a PGA-CNTs sweat glucose sensor. PGA films with a porous three-dimensional (3D) network structure were prepared by solvent evaporation, CNTs were deposited to obtain PGA-CNTs electrodes, and GOx was adsorbed through the high specific surface area structure of the 3D network. The results confirmed that the mesh structure formed by carbon nanotubes attached to PGA could substantially improve the charge transfer ability, and a considerable amount of GOx could be stably immobilized in the three-dimensional structure of the electrode. The PGA-CNTs sweat glucose sensor has excellent conductivity stability under bending and accurately detects glucose in the presence of other interference. The linear range of glucose response is 20–300 μM, and the sensitivity is 78.45 μA mM −1 cm −2 . Compared to existing products, the PGA-CNTs biosensors are more competitive in detection performance and cost.

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Small · 2025 · IF 12.1

Targeted Intracellular Copper Reservoir Enhances Liver Cancer Immunotherapy

Tianao Xie,Yukai Shan,Win Topatana,Taorui Yang,Ruijing Shen,Shijie Li,Jiadong Chen,Yiyuan Zhu,Ziyi Lu,Yeling Liu,Tianen Chen,Yujie Gao,Yuchao Sun,Xiujun Cai,Sarun Juengpanich,Mingyu Chen

Hepatocellular carcinoma (HCC) is commonly classified as a “cold tumor” due to its low immunogenicity and poor response to conventional immunotherapies. Reprogramming the tumor immune microenvironment (TIME) via cuproptosis presents a promising strategy to enhance immunotherapies. Herein, sono-activatable N,N,N’,N’-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN)-encapsulated cancer-targeted nanoparticles (STCNs) designed to modulate the TIME and potentiate immunotherapy through endogenous cuproptosis are reported, termed “endogenous cuproptosis immunopromotion”. STCNs are rapidly internalized by HCC via folate-mediated endocytosis, and ultrasound irradiation triggers the release of TPEN. TPEN then chelates Cu 2 ⁺ from superoxide dismutase, initiating a Fenton-like reaction induced by glutathione that produces reactive oxygen species (ROS) and Cu⁺. This cascade induces cuproptosis and immunogenic cell death (ICD), promoting robust cytotoxic T lymphocyte infiltration in HCC. The combination of STCNs with anti-programmed cell death protein 1 (PD1) therapy demonstrates significant anti-tumor efficacy in vivo. Moreover, this strategy exhibits similar effectiveness in other solid tumor models, underscoring its broad therapeutic potential. These findings provide a promising framework for enhancing immunotherapy in cold tumors, paving the way for future cancer treatments.

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Bioengineering & Translational Medicine · 2024 · IF 6.1

Two-pronged reversal of chemotherapy resistance by gold nanorods induced mild photothermal effect

Qi Shang,Ziyan Chen,Jing Li,Mingmei Guo,Jiapei Yang,Zhu Jin,Yuanyuan Shen,Shengrong Guo,Feihu Wang

Chemotherapy treatment outcomes are severely restricted by multidrug resistance (MDR), in which tumors develop a multiple cross-resistance toward drug involving the pump and nonpump resistance mechanisms, resulting in drug efflux and defending against drug toxicity. Herein, we constructed a pH and near infrared (NIR) light responsive nanomedicine DOX@FG based on gold nanorods (GNRs) that demonstrated the potential to improve chemotherapy outcomes by overcoming MDR. DOX@FG was constructed by conjugating folic acid (FA) and doxorubicin (DOX) derivatives onto GNRs, where the DOX derivatives possessed an acid-labile hydrazone bond. Stimulated by the acidic media in endocytic organelles, DOX@FG exhibited a responsive dissociation for the controlled release of chemotherapeutic DOX. Surprisingly, we found the mild photothermal effect elicited by GNRs under NIR irradiation simultaneously inhibited the pump and nonpump resistance mechanisms, enhancing the intracellular DOX accumulation and sensitizing the cancer cells to DOX, collectively amplify the chemotherapy efficacy and delay the MCF-7/ADR breast tumor growth. This intelligent DOX@FG nanomedicine with the potential for two-pronged reversal of MDR may provide a prospective way to encourage chemotherapy efficacy.

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JOURNAL OF NANOBIOTECHNOLOGY · 2025 ·Vol. 23 ·期 1 ·1-24 · IF 12.6

Engineered Panax notoginseng polysaccharide micelles inhibit macrophage polarization and delay the progression of rheumatoid arthritis via JAK2-STAT3 signaling pathway

Yu Yang,Kong Liang,Guo Rui-bo,Zhang Ya-ni,Li Shu-tong,Zhang Feng-yuan,Wang Xin,Liu Yang,Li Xiu-Ying,Li Xue-tao

Background The imbalance of macrophage polarization plays a pivotal role in the progression of rheumatoid arthritis (RA). Reprogramming macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype is considered a promising therapeutic strategy. Methods To address this challenge, Panax notoginseng polysaccharides (PNP) with varying molecular weights were chemically conjugated with deoxycholic acid (DC) to obtain amphiphilic conjugates (PNP-DC), which self-assembled into micelles (PNP-Ms). After screening for optimal molecular weight, folic acid (FA) was introduced onto the micelle surface, and Polyphyllin I (PPI) was encapsulated to form FA-modified, PPI-loaded micelles (FA-PPI-Ms) with macrophage-targeting capability. Results FA-PPI-Ms showed enhanced cellular uptake via FA receptor–mediated endocytosis and effectively eliminated reactive oxygen species (ROS), reduced inflammatory cytokine production, and exhibited good biosafety. In vivo, FA-PPI-Ms significantly alleviated joint swelling and inflammation in RA rat models. Mechanistic studies based on RNA sequencing and experimental validation revealed that FA-PPI-Ms suppressed the JAK2/STAT3 signaling pathway, thereby promoting M2 macrophage polarization and restoring the M1/M2 balance. Conclusion This study presents a novel FA-PPI-Ms delivery system for targeted macrophages. By modulating polarization through inhibition of JAK2/STAT3 signaling, the system offers a promising therapeutic strategy for RA and potentially other inflammatory diseases.

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ACS Applied Nano Materials · 2025 · IF 5.5

Zn2SiO4 Hollow Nanoparticles with Persistent Luminescence: Implications for Drug Loading

Mengxia Xu,Shengqian Wang,Chaochao Tao,Songsong Ding,Hualan Xu,Shengliang Zhong

Here, we report a synthesis method of Zn2SiO4@SiO2 hollow nanoparticles with adjustable thickness. A core–shell structured coordination polymer (CP) @ silica precursor was constructed by encapsulating silica on the surface of the CP through surface adsorption induced self-assembly. Then, the ideal shapes and large hollow cavities were produced through high-temperature calcination, and the formation process of hollow spheres was studied. Thanks to the hollow structure of the material, it has excellent drug loading capacity. It is worth noting that the thickness of the silica shell can be modulated by adjusting reagent amounts, calcination temperature, and time. Furthermore, this method exhibits broad applicability and can be extended to the synthesis of other hollow metal oxide materials. Persistent luminescence (PresL) was achieved through a simple ion-doping strategy. Notably, the silica shell thickness was found to regulate luminescence performance, and its underlying mechanism was further explored. This study not only establishes a synthetic route for designing hollow-structured PersL materials, but also offers perspectives on regulating the structure–performance relationships in multiphase composite materials. We hope the methodology developed and luminescent properties observed in this study will inspire the development of other innovative architectures integrating both physiological compatibility and theranostic capabilities.

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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Targeting and reversing tumor acidic microenvironment with bacterial cellulose-based micelles to enhance immune infiltration

Shuangjun Li,Ruyue Shi,Yankun Liu,Mingcong Niu,Zhicun Liu,Zhongjuan Wang,Jiwang Gao,Hongda Cai,Zhuyu Zhou,Shengnan Li,Xiuhua Zhao

Immune cells infiltrating tumors play a pivotal role in tumor progression regulation; however, their functionality is frequently suppressed by the acidic conditions of the tumor microenvironment (TME). Targeting and reversing tumor acidity holds significant potential for enhancing the efficacy of immunotherapy. Here, we present a proof-of-concept study on tumor acidity-reversal therapy mediated by bacterial cellulose-targeted micelles to promote M2 macrophage repolarization to M1 macrophages and restore the anti-tumor function of T cells. Our strategy utilizes a bacterial cellulose (BC) composite modified with folic acid (FA) and chrysin (BY), loaded with lactic acid-neutralizing chemotherapeutic vincristine (VCR) and lactate dehydrogenase inhibitor GNE-140, to self-assemble into tumor-targeted nanoparticles. Post-treatment, FA-BC-BY@VCR@GNE-140 demonstrated notable efficacy in reversing tumor acidity, inducing tumor cell death, mitigating immunosuppression, and stimulating host adaptive immunity. This approach represents an innovative strategy for synergizing chemotherapy and immunotherapy to combat tumor progression.

CAS / MDL: 59-30-3
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