DRUG DELIVERY
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2019
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IF 3.829
Guofei Li,Limei Zhao
Tumor microenvironment is closely related to the occurrence and development of liver cancer. Tumor-associated macrophages (TAMs) are an important part of tumor microenvironment promoting tumor deterioration and metastasis by inhibiting immune cells. Previous studies showed that PI3Kγ inhibitor could reverse the phenotype of TAMs, relieve immunosuppression and sensitize chemotherapy drugs, suggesting that the combination of PI3Kγ inhibitor and chemotherapeutics is likely to bring new breakthroughs in the treatment of liver cancer. Based on it, this paper builds HES-TG100-115-CDM-PEG micelles with tumor microenvironment responsiveness that simultaneously loaded sorafenib and TG100-115 to synergistically treat liver cancer. Pharmacokinetic study showed that the prepared micelles had longer half-life than that of the free drug solutions, which was favorable for high propensity of extravasation through tumor vascular fenestrations. Under low pH and high α-amylasereductive conditions, micelles could depolymerize quickly due to the sensitivity of bonds and enhance significantly cytotoxic activity against Hep-3B liver cancer cell. Additionally, micelles demonstrated higher levels of antitumor efficiency and better tolerance against nude mouse with Hep-3B cell than the free drug solutions. These findings reveal that HES-TG100-115-CDM-PEG micelles are a promising drug delivery system in clinical comprehensive therapy of liver cancer.
研究领域:
药学
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肿瘤学
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生物医学工程
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
An Gao,Fengyu Wang,Xiaonan Cui,Jin Wu,Chunyang Sun,Zhaoxiang Ye
Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising strategy for combination with chemotherapy in cancer treatment. However, the rational design of delivery systems capable of simultaneously inducing ferroptosis, enhancing chemotherapy efficacy, and reducing systemic toxicity remains a substantial challenge. Herein, we developed a reactive oxygen species (ROS)-responsive, ionically crosslinked chitosan/hyaluronan polyelectrolyte nanogel for targeted chemo-ferroptosis combination therapy. In this system, hyaluronic acid (HA) was first esterified with 1,2-bis (2-hydroxyethylthio) ethylene (BE) and subsequently conjugated with methotrexate (MTX) through a ROS-cleavable linkage, yielding an anionic HA- BE -MTX polymeric prodrug. Protonated chitosan (CS) served as the cationic polymeric component, while sodium tripolyphosphate (TPP) further stabilized the nanogel network through ionic crosslinking. Sorafenib (SOR), a ferroptosis inducer, was physically encapsulated during the ionotropic gelation process. The resulting R-NG MS nanogels were designed to maintain colloidal stability under physiological conditions and to undergo ROS-triggered network loosening and drug release in the tumor microenvironment, where oxidative stress is elevated. This dual-delivery system enabled ROS-responsive MTX release and SOR-mediated ferroptosis induction, thereby promoting ROS accumulation, glutathione depletion, GPX4 suppression, lipid peroxidation, and apoptosis in breast cancer cells. In vivo studies demonstrated that R-NG MS efficiently accumulated in 4T1 tumors through prolonged circulation and HA-CD44-mediated tumor targeting, achieving a tumor growth inhibition rate of 75.85% with reduced systemic toxicity compared with free drug treatment. These findings demonstrate that ionically crosslinked CS/HA-based polyelectrolyte nanogels provide an effective and selective platform for ROS-responsive chemo-ferroptosis combination therapy.
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高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2026
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IF 5.2
Xiaoxi Gao,Dehai Hou,Tianyu Ma,Sizhuo Liu,Ruiping Wang,Yang Ping,Jin Su
A synergistic nano-strategy co-delivering sorafenib and berberine to overcome resistance and reduce toxicity. • Optimized nanostructured lipid carriers with high drug loading, sustained release, and good stability were successfully prepared. • Pharmacokinetics showed significantly enhanced oral bioavailability (4.59-fold and 2.28-fold for SORB and BBR). • Superior antitumor efficacy and biosafety were systematically verified both in vitro and in vivo. Sorafenib (SORB) is a first-line drug for advanced hepatocellular carcinoma, but its clinical use is limited by poor water solubility, low oral bioavailability, and drug resistance. Berberine (BBR) has been shown to reverse multidrug resistance and enhance drug sensitivity. Here, we designed a nanostructured lipid carrier co-loaded with SORB and BBR (SBER NLC). The optimized formulation had a particle size of 123.17 ± 3.28 nm, PDI of 0.211 ± 0.012, and zeta potential of −18.30 ± 0.95 mV. Encapsulation efficiencies were 78.77 ± 0.93% (SORB) and 79.58 ± 1.04% (BBR), with drug loadings of 1.75 ± 0.06% and 1.28 ± 0.13%, respectively. SBER NLC showed stable storage properties and sustained release in simulated gastrointestinal fluids. Pharmacokinetic studies demonstrated significantly enhanced oral bioavailability of both drugs compared with free drug suspension. In vitro, SBER NLC exhibited stronger cytotoxicity and migration inhibition against HepG2 cells, while the blank carrier was nontoxic. In a HepG2 xenograft mouse model, SBER NLC achieved the strongest tumor suppression without causing body weight loss or major organ damage, and induced extensive nuclear pyknosis and necrosis in tumor tissue. This study provides an efficient nano-delivery strategy for combined SORB and BBR in hepatocellular carcinoma treatment. Download: Download high-res image (226KB) Download: Download full-size image
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BIOORGANIC & MEDICINAL CHEMISTRY
·
2026
·
IF 3.5
Shuxiao Feng,Zongluo Zhang,Xuan Zhong,Jiahao Chen,Kejia Ren,Yishuai Wu,Tianxin Ji,Tong Wu,Shouren Zhang,Shiyong Xin
Ring-opened scaffolds from the benzisoselenazolone (BISZ) core offers a promising strategy for developing novel selenium-containing anticancer agents. • Novel 11 symmetric bis-open-ring ebselen analogues were synthesized, and 3d exhibited antiproliferative activity against seven human cancer cell lines, with IC₅₀ values ranging from 1.55 to 14.33 μM. Compound 3d also inhibited angiogenesis in transgenic zebrafish, reducing subintestinal vessel area by 25.6% and intersegmental vessel number by 15.8%. • Virtual screening and 100 ns molecular dynamics simulations revealed stable binding of 3d to human methionine aminopeptidase 2 (MetAP2), with a MM-GBSA binding free energy of −22.14 kcal/mol. • The dual inhibitory effects on cancer cell proliferation and angiogenesis suggest a promising mechanism for new ebselen open-ring analogue 3d as an anticancer agent. Optimizing ring-opened scaffolds from the benzisoselenazolone (BISZ) core offers a promising strategy for developing novel anticancer agents. Herein, eleven new ebselen analogues ( 3a–k ) featuring a symmetric bis-open-ring scaffold were synthesized and evaluated for in vitro antiproliferative activity against seven human cancer cell lines. Results shown compound 3d was the most potent across all seven tested panels, including lung carcinoma A549 (IC 50 = 3.75 μM), esophageal KYSE-30 (1.55 μM), hepatocellular HCCLM3 (5.57 μM), prostate PC3 (2.77 μM), colorectal HCT116 (14.12 μM), hepatocellular HepG2 (14.33 μM), and breast MDA-MB-231 (8.28 μM). At 6.25 μM, 3d significantly inhibited angiogenesis in transgenic zebrafish, reducing subintestinal vessel area by 25.6% ( p < 0.001) and intersegmental vessel number by 15.8% ( p < 0.01), suggesting a potential anti-angiogenic activity against cancer. Docking and MD simulations suggested a possible interaction of 3d to MetAP2. A novel ring-opened ebselen scaffold with potent anti-angiogenic activity against cancer: synthesis, biological evaluation, and molecular docking. Download: Download high-res image (118KB) Download: Download full-size image
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ACS Nano
·
2026
·
IF 17.3
Fu Fangqin,Ge Yuting,Hu Xuemei,Huang Yeqi,Yang Wenhua,Fan Hao,Ding Jiayi,Zhou Luying,Wang Zhicheng,Bonnicel Fanny,Lieberwirth Ingo,Mailänder Volker,Crespy Daniel,Landfester Katharina,Jiang Shuai
Cholesterol
is a key determinant of membrane stability and fluidity
in both natural and synthetic lipid systems. Although widely used,
its content varies greatly among commercial liposomes, and its regulatory
effects on biological interactions remain insufficiently understood.
Here, we reveal that cholesterol content critically governs the protein
corona composition and binding affinity of liposomes, thereby dictating
their cellular interactions and in vivo fate. Complement
proteins exhibit a biphasic adsorption pattern that modulates monocyte
and Kupffer cell uptake and systemic clearance. High cholesterol levels
enrich apolipoproteins, particularly ApoE, promoting hepatocyte targeting,
liver accumulation, and enhanced uptake by dendritic cells in blood
and spleen. In contrast, low-cholesterol liposomes form albumin-dominated
coronas that favor uptake by liver sinusoidal and pulmonary endothelial
cells, leading to preferential lung accumulation. Notably, cholesterol-rich
liposomes significantly suppress hepatocellular carcinoma progression
through improved liver targeting and prolonged circulation. These
findings identify cholesterol as a pivotal regulator of serum protein
interactions and biodistribution, providing valuable insights for
the rational design of efficient, organ-specific liposomal drug delivery
systems.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2025
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IF 5.6
Cheng-Lei Li,Wen-Zhong Zhang,Rui-Rui Zhao,Jing-Qing Le,Bing-Chen Zhang,Huan-Zhang Xie,Yu-Sheng Lu,Jing-Wei Shao
Immune checkpoint blockade (ICB) holds broad application prospects in tumor treatment. However, the poor immunogenicity and the adaptive resistance cells severely limit the clinical efficacy. Immunogenic cell death (ICD) can sensitize the cells which were initially lower responsive to ICB. Based on this, we reported a metal coordination co-assembly nanocomposite (SIF NPs), which can enhance cancer immunotherapy by strengthening ICD induction through inducing ferroptosis-photo-chemo. The SIF NPs possess excellent biocompatibility and stability, and exhibit good PTT and PDT effects both in vitro and in vivo . The SIF NPs disrupt redox homeostasis and induce ferroptosis by consuming glutathione (GSH), downregulating the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), and enhancing the generation of lipid hydroperoxides (LPO). Importantly, SIF NPs trigger an ICD cascade via inducing the cell death, thus enhancing the immunogenicity of tumors. In a tumor-bearing mice model, the synergistic therapy of SIF NPs and anti-PD-L1 antibody demonstrated a powerful inhibition effectiveness on bilateral tumors and instigated a long-time immune memory effect. This study indicates that the combined treatment of ferroptosis-photo-chemo and immunotherapy possess promising application prospects.
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高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Dong Wang,Mengrong Li,Tingting Dai,Xiangyu Zhang,Di Chen
A rapid, sensitive, and green sample preparation method based on polypropylene fiber-supported liquid-phase microextraction followed by liquid chromatography–tandem mass spectrometry was developed for the determination of tyrosine kinase inhibitors in plasma. Commercial oil absorbent pads composed of polypropylene fibers were used to support n-octanol as the extraction phase. The high chemical purity of the polypropylene fiber minimized background interference, enabling reliable trace-level analysis. The in-syringe format allowed simple push–pull operation, and extraction conditions were optimized for maximum efficiency. The method demonstrated excellent linearity (R 2 > 0.995), low limits of quantification (0.067–3.0 ng/mL), and high precision, with intra- and inter-day recoveries ranging from 79.5 % to 113.6 % and relative standard deviations below 14.2 %. A blinded spiked sample analysis confirmed the method’s reliability for clinical application. The greenness of the method, as evaluated by five green assessment tools, demonstrated excellent environmental compatibility. Overall, the proposed in-syringe polypropylene fiber-supported liquid-phase microextraction method offers a simple, cost-effective, and environmentally sustainable solution for the analysis of tyrosine kinase inhibitors in complex biological matrices.
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高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Ying Xu,Xiaojun Cai,Jianrong Wu,Yuanyi Zheng,Yaotai Wang
Lipid nanoparticles (LNPs) possess liver-targeting properties that increase drug accumulation in liver cancer cells, thereby mitigating drug resistance and systemic toxicity. However, critical limitations such as off-target effects, rapid clearance, and poor specificity hinder their clinical translation. Inspired by the tumor-targeting ability of bacteria, we constructed a multifunctional engineered bacteria system combining LNPs with probiotics by electrostatic adsorption. Specifically, the surface of Bifidobacterium longum (BL) was modified with sorafenib-loaded LNPs (designated PSI LNPs), enabling precise delivery of lipid nanomedicines to tumor sites. Meanwhile, ultrasound irradiation facilitated drug release within the tumor and improved efficacy. On the one hand, we used fluorescence imaging to observe and monitor live-engineered bacteria. Compared to the single PSI LNPs group, the tumor accumulation of lipid nanomedicines loaded with engineered bacteria exhibited a 66% increase. The results demonstrated that the engineered bacteria not only augmented the accumulation of nanomedicines within the tumor but also prolonged the retention time for a sustained effect on the tumor. On the other hand, we further explored synergistic immune system activation by Bifidobacterium and sonodynamic therapy, which stimulated dendritic cell maturation, T cell infiltration, and CD8 + T cell activation. In conclusion, this delivery strategy of engineered bacteria targeting the tumor microenvironment is expected to overcome the limitations of conventional LNPs and provide a promising approach for treating hepatocellular carcinoma.
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高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2026
·
IF 9.6
Yong Huang,Tao Quan,Bowen Li,Chaohui Zhen,Haiqian Zhang,Zhiyao Li,Chongzhi Wu,Rui Liang,Lihe Sun,Xin Xie
Triple-negative breast cancer (TNBC), lacking effective therapeutic targets, is highly aggressive, prone to metastasis, and associated with poor prognosis, highlighting the necessity for innovative therapeutic strategies. Ferroptosis, an emerging form of iron-dependent programmed cell death, presents a promising treatment approach. However, its effectiveness is often hindered by adaptive resistance within the tumor microenvironment and inefficient drug delivery. To address these limitations, the glutathione (GSH)-responsive disulfide linker (-SS-) was utilized to engineer rhein (Rhe, chemotherapeutic agent) and ferrocene (Fc, ferroptosis booster) into the self-assembling small-molecule prodrug RSSF. Sorafenib (SOR), a ferroptosis inducer, was stably loaded into RSSF via a simple nanoprecipitation method, yielding the newly nanoprodrug designated as SOR@RSSF nanoparticles (NPs) for the combination therapy of TNBC. SOR@RSSF NPs exhibit markedly enhanced cellular uptake and enable the highly specific and synchronous release of Rhe, Fc, and SOR in response to intracellular GSH levels. Notably, Fc efficiently generates hydroxyl radicals (•OH) through the Fenton reaction, thereby inducing pronounced oxidative stress, while SOR concurrently impaired the cellular ferroptosis defense machinery. Combined with the chemotherapeutic activity of Rhe, the resulting lipid peroxide (LPO) accumulation and GSH depletion synergistically trigger both ferroptosis and apoptosis selectively in tumor cells. In a 4T1 tumor-bearing mouse model, SOR@RSSF NPs significantly inhibited tumor progression while maintaining a favorable biosafety profile. Overall, this study presents a promising ferroptosis-sensitizing strategy using a nanoprodrug delivery system for combination therapy against TNBC.
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2026
·
IF 3.8
Wang Dong,Li Mengrong,Zhang Xiangyu,Chai Shiwei,Chen Di
A novel ultrasound-assisted magnetic sorbent–wrapped stick dip extraction (UA-MSWS-DE) method was developed for the batch-scale determination of seven tyrosine kinase inhibitors (TKIs) in human plasma. The extraction device was fabricated by immobilizing octadecylphosphonic acid–functionalized magnetic nanoparticles onto flame-sealed glass capillaries embedded with magnets. Ultrasonic-assisted dip extraction was used to extract TKIs from diluted plasma, followed by quantification via liquid chromatography–tandem mass spectrometry (LC-MS/MS). Key extraction parameters were systematically optimized, yielding the following optimal conditions: sample pH 5.0 and volume 1.0 mL, sorbent particle size 20 nm and dosage 10 mg, extraction time 20 min, and desorption with 150 µL of ethanol for 8 min. The method demonstrated excellent linearity ( R 2 ≥ 0.99), low limits of quantification (0.1–5.0 ng/mL), and good intra-/inter-day precision (RSDs < 14.95%). The accuracy in blinded plasma samples, tested at 0.25–25% of the studied concentration range, ranged from 87.13 to 112.33%. Compared to conventional magnetic dispersive solid-phase extraction, the UA-MSWS-DE strategy simplifies handling and is designed to facilitate potential parallel processing using only an ultrasonic bath. Five greenness metrics confirmed the method’s high sustainability. Furthermore, the modular design enables adaptation to other analytes by modifying the sorbent coating, making UA-MSWS-DE a sensitive, green, and automation-ready method for therapeutic drug monitoring. Graphical
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JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
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2026
·
IF 14.3
Jia-Rui Du,Mu-Le Tu,Yong-Xu Xia,Yuan-Qiang Lin,Rui Yang,Chang Weng,Yi Liu,Hao Zhang,Hui Wang,Wen-Jie Feng,Deng-Ke Teng
Nanovaccines based on immunogenic cell death (ICD) present a promising strategy in tumor immunotherapy, serving as a bridge connecting tumor cell death to the induction of anti-tumor immunity. However, their efficacy is severely limited by the immunologically silent nature of apoptosis-dependent ICD and the immunosuppressive tumor microenvironment (TME). In this work, we designed a metal‒polyphenol network nanovaccine (SRF@FeShik-cGAMP/HA). Upon reaching the tumor tissue through specific targeting, the nanovaccines disassemble within the tumor cells, releasing the Fenton reaction catalyst ferrous iron (Fe 2+ ), the system Xc- inhibitor sorafenib (SRF), and necroptosis inducer shikonin. Fe 2+ , SRF, and shikonin collectively promote the accumulation of lipid peroxide and amplify ferroptosis by providing an exogenous iron source, inhibiting glutathione biosynthesis, and boosting reactive oxygen species production, respectively. Meanwhile, shikonin induces necroptosis. The combination of ferroptosis and necroptosis overcomes the limitation of tumor immune silencing and triggers a strong ICD. Simultaneously, the immune adjuvant 2'3'-cyclic-GMP-AMP (cGAMP) activates the STING pathway, reversing the immunosuppressive TME and enhancing the anti-tumor immune response mediated by ICD. The synergistic action of ferroptosis, necroptosis, and the STING pathway produces a cascade of antitumor immune responses and establishes long-term immune memory. This nanovaccine demonstrates promising therapeutic effects in primary, orthotopic, and recurrent hepatocellular carcinoma (HCC) models. Collectively, our findings present a cancer immunotherapy strategy that exploits dual ferroptosis and necroptosis induction to trigger ICD, bypassing the limitations of apoptosis-dependent pathways. This strategy coordinates with the STING pathway to achieve potent antitumor immunity, providing a promising paradigm for HCC treatment, and offering a promising and translatable path for clinical development.
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CHEMICAL ENGINEERING JOURNAL
·
2024
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IF 13.3
Chun-Mei Lai,Jia Xu,Bing-Chen Zhang,Shao-Hua He,Jing-Wei Shao
Ferroptosis, an emerging cell death mode discovered in recent decades, is characterized by lipid peroxidation during cell death, usually manifested as iron accumulation. However, the forthright delivery of iron species will cause adverse detrimental effects such as anaphylactic reactions in routine tissues. So far, studies on cellular ferroptosis by employing bio-derived nanomaterials have rarely been acquired. Herein, we reported carbon dots (CDs)-based biocompatible enzymes with negligible toxicity from a representative hepatoprotective triterpenoid natural product ursolic acid (UA) with acknowledged antitumor activity. We observed that CDs presented distinct GSH oxidase-like characteristics and then contributed ferroptosis of carcinoma cells by interfering with the GPX4-catalyzed lipid repair system. After the CDs were assembled with UA, the obtained denoted as UCDs integrated multi-model therapy into one, resulting in enhanced therapeutic efficacy, reduced adverse effects, and optimized clinical outcomes. In vivo , the UCDs hysterically inhibited tumor growth in hepatoma H22-bearing mice with inconsequential toxicity. Exceptionally, UCDs enlisted a large number of tumor-infiltrating immune cells, including T cells, NK cells, and macrophages in H22 tumor-bearing mice, consequently transforming “cold” into “hot” tumors to activate systemic anti-tumor immune responses. Meanwhile, UCDs could also awfully suppress the H22-LUC tumor growth in orthotopic xenograft mouse models. Collectively, our research commends that the drug delivery systems based on natural-products-derived CDs can function as biocompatible enzymes for antitumor treatment and may facilitate the advancement of nanotechnology-based immunotherapeutics. It is extremely anticipated that such ferroptosis-like designing in nano-catalytic medicine would be favorable for future development in cancer-therapeutic regimens.
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