SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2026
·
IF 4.8
Chen Cheng,Wenhe Pan,Tingyang Xing,Jiaying Shen,Yaoyao Dong,Yitie Xu,Yingyi Zhao,Chenyi Wang,Wei Sun
This study addresses the critical need for rapid and sensitive detection of cisplatin, a widely used chemotherapeutic agent often limited by severe toxicities and drug resistance. Traditional detection methods are time-consuming and unsuitable for point-of-care applications. We developed an surface-enhanced Raman scattering (SERS) platform leveraging novel gold nanooctahedra‑silver nanocube core-shell (AuNO@AgNC) nanoparticles. Finite-difference time-domain (FDTD) simulations predicted a local field enhancement factor of 153.30 for the isolated nanostructure and further supported the use of 633 nm excitation by revealing a red-shifted coupled dimer plasmon mode near 644 nm in the film-relevant configuration. A facile oil-liquid interfacial self-assembly method enabled the fabrication of highly uniform SERS films. Evaluation with Rhodamine 6G (R6G) demonstrated a linear detection range from 0.5 nM to 500 nM, an impressive SERS enhancement factor of 1.57 × 10 8 , and excellent signal reproducibility (relative standard deviation, RSD, of 14.85%). Applying this platform for cisplatin detection yielded a calibration range from 5 nM to 1000 nM, with an S/N-based limit of detection (LOD) of 1.9 nM and a limit of quantification (LOQ) of 6.5 nM. This research highlights the significant potential of our AuNO@AgNC SERS substrate for quantitative monitoring of low-concentration anticancer drugs.
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高影响因子
TOXICON
·
2026
·
IF 2.8
Jing Li,Xiaoxiao Wang,Liya Tu,Yufeng Chen
Ovarian cancer (OC) exhibits the highest mortality rate among gynecological cancers, and the development of chemotherapy resistance serves as the primary cause of patient recurrence and death. Natural products hold promise in reversing cisplatin (DDP) resistance. Trigonelline is a natural alkaloid possessing anti-tumor activity; however, it remains uncertain whether it can reverse DDP resistance in OC. In this study, DDP-resistant OC cell lines SKOV-3/DDP and A2780/DDP were successfully established. Cells were treated with non-toxic concentration of trigonelline in combination with DDP, and the molecular mechanism was investigated through the overexpression of Nrf2. Cell viability was detected to assess the sensitivity of the cells to DDP. Mitochondrial damage was evaluated by observing mitochondrial morphology, measuring mitochondrial membrane potential, ATP production, and ROS. Ferroptosis was assessed by detecting the levels of lipid peroxidation, MDA, SOD, Fe 2+ , and GSH/GSSG ratio in the cells. Additionally, the expression levels of ferroptosis-related proteins, namely Nrf2, HO-1, GPX4, and SLC7A11, were also detected. The results indicated that the utilization of low-concentration trigonelline exerted no toxic influence on OC drug-resistant cells, and instead potentiated the cytotoxicity of DDP against these cells. Furthermore, in comparison with the treatment using DDP alone, the combined treatment of trigonelline and DDP induced more severe mitochondrial damage and ferroptosis in drug-resistant cells. This led to the accumulation of ROS, notable increases in lipid peroxidation, MDA, and Fe 2+ levels within the cells, while decreasing SOD activity and the ratio of GSH/GSSG, and down-regulating the expression of Nrf2, HO-1, GPX4, and SLC7A11 proteins. Nevertheless, the overexpression of Nrf2 reversed the combined effect of trigonelline and DDP. These results indicate that trigonelline reverses DDP resistance in OC cells by promoting ferroptosis via the regulation of the Nrf2/GPX4 signaling pathway.
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FREE RADICAL BIOLOGY AND MEDICINE
·
2026
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IF 8
Huaqiu Li,Wenxiu Xing,Yuyuan Dai,Shaoyi Cao,Xinyi Yang,Yue Zhang,Xiangfeng Zeng,Hongjiao Liu,Xiaoping Wu
Ovarian cancer (OC) is a fatal female malignancy, and Cisplatin resistance severely impacts the clinical management of epithelial ovarian cancer (EOC), the most prevalent histological subtype accounting for over 90% of cases. Exploration of novel effective targets and drugs for treatment of cisplatin-resistant EOC is urgently needed to address the tremendous challenge. In this study, we screened a Traditional Chinese Medicine (TCM) library including 978 monomers and found that Raddeanin A (RA) extracted from Anemone raddeana Regel displayed the powerful cytotoxic effect on cisplatin-resistant EOC cells. Further investigations revealed that RA had potential of inducing ferroptosis via binding to an evolutionarily conserved scaffold protein, VEPH1. Bioinformatics analysis combined with RA-sepharose pull-down assay and immunoprecipitation confirmed that RA interacted with two sites of VEPH1, site 1 (S1) at 212-217 aa and site 2 (S2) at 579-651 aa, and S1 was also involved in VEPH1 binding to and promoting lats1 activation. Moreover, RA bound to and enhanced VEPH1 degradation through the proteasome pathway, and meanwhile inhibited the interaction between VEPH1 and lats1, which in turn suppressed lats1 activation, promoted YAP nuclear translocation to up-regulate the expression of ferroptosis-driven proteins, TFRC and ACSL4, resulting in an imbalance of intracellular iron homeostasis, as well as promotion of lipid peroxidation, and thus inducement of ferroptosis in cisplatin-resistant EOC cells. Importantly, the in vivo results confirmed that RA induced ferroptosis and dramatically suppressed the growth of A2780/DDP transplanted tumours. Taken together, we revealed for the first time that VEPH1 is the direct target for RA, and ferroptosis contributes to RA-triggered anti-tumour effect on cisplatin-resistant EOC, which provides new insights into the therapeutic application of RA against EOC chemoresistance.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2026
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IF 5.9
Xiaoyi Cheng,Xiang-Fu Du,Jing Long,Yangyi Nie,Yuhan Du,Luyao Cheng,Cairong Li,Mei-Xia Zhao,Yuxiao Lai,Wei Zhang
Based on nanomedicine, tumor microenvironment modulation and combination therapy has become an important approach for efficient tumor treatment. Herein, we designed a multifunctional nanoparticle through layer-by-layer strategy. Dopamine self-polymerization forms cisplatin (CDDP) prodrugs encapsulated polydopamine (PDA) core, with a manganese dioxide (MnO 2 ) shell formed on the surface through in situ coating. Targeting molecule hyaluronic acid (HA) is assembled on the surface through electrostatic and coordination interactions, constituting the nanomedicine HMPP NPs. After targeted internalization by tumor cells, MnO 2 catalyzes the decomposition of intracellular hydrogen peroxide (H 2 O 2 ) to generate oxygen (O 2 ). Meanwhile, MnO 2 and CDDP prodrug deplete the intracellular glutathione (GSH) to prevent the detoxification effect to CDDP. Therefore, at the first stage HMPP NPs could circumvent the CDDP resistant tumor microenvironment by alleviating tumor hypoxia and GSH depletion. Subsequently, HMPP NPs exert photoacoustic (PA) imaging guided combinational chemo-phototherapy, leveraging the exceptional photothermal properties of PDA. Ultimately, HMPP NPs-mediated combination therapy demonstrates efficient killing of cancer cells in vitro and achieves significant tumor suppression effects in vivo . All in all, this work underscores the importance of nanomedicine mediated tumor microenvironment modulation and combination therapy in combating drug resistance for effective tumor treatment.
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Cancer Nanotechnology
·
2022
·Vol. 13
·期 1
·1-16
·
IF 7.917
Chen Xiaoxiao,Wang Lulu,Liu Sijia,Luo Xuezhen,Wang Kai,He Qizhi
Developing multifunctional composites has received widespread attention for cancer treatment. Herein, a metal–phenolic network (MPN)-based composite loading with chemotherapy agents (TAFP) exhibits high anti-tumor therapeutic efficacy via photothermal therapy (PTT), chemo-dynamic therapy (CDT), and chemotherapy. The nanocomposite was formed by mixing the chemotherapeutic drugs (cisplatin, DDP) into the tannic acid (TA) and Fe 3+ network (TAFe) to integrate the synergistic effect of PTT, CDT, and chemotherapy. Due to the acidic tumor microenvironment, the active substances could be released with the degradation of the metal–phenolic network, and the released DDP would induce the chemotherapy. More importantly, the released TA under the acidic environment could increase iron bioavailability by converting Fe 3+ to Fe 2+ , which converts hydrogen peroxide (H 2 O 2 ) to highly toxic hydroxyl radical via the Fenton reaction. Meanwhile, the heat generated from TAFP after near-infrared (NIR) laser irradiation could enhance the therapeutic effect of CDT and chemotherapy. Furthermore, the composite exhibited unique anticancer efficacy in vivo with low toxicity. Collectively, this work may facilitate the development of metal–phenolic network-based photothermal agents for clinic anti-tumor applications.
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高影响因子
MOLECULES
·
2022
·Vol. 27
·期 12
·3823
·
IF 4.927
Meng Zhou,Yanpeng Dai,Yong Ma,Yi Yan,Min Hua,Qi Gao,Xue Geng,Qian Zhou
Acute kidney injury (AKI) induced by cisplatin (CP), a first-line anticancer drug for chemotherapy, is common. To date, there is an urgent need to find effective treatments to reduce the nephrotoxicity caused by CP. Meanwhile, the restoration of mitochondrial dysfunction shows potential to be used as an adjunct to conventional therapeutic strategies. This study found that liquiritigenin can ameliorate mitochondrial dysfunction and acute kidney injury induced by CP in mice. The intraperitoneal injection of 15 mg/kg body weight liquiritigenin for 2 days markedly protected against CP-induced mitochondrial dysfunction, restored renal tubule and mitochondrial morphology, decreased blood Scr and BUN levels, and decreased cell apoptosis. Furthermore, the elevated expression of SIRT3 induced by liquiritigenin, which can be upregulated by NRF2, was confirmed in vivo and in vitro. The underlying protective mechanisms of liquiritigenin in CP-induced nephrotoxicity were then investigated. Molecular docking results showed that liquiritigenin has potent binding activities to KEAP1, GSK-3β and HRD1. Further results showed that liquiritigenin induced the nuclear translocation of NRF2 and increased the levels of mitochondrial bioenergetics-related protein such as PGC-1α, and TFAM, which are related to NRF2 activity and mitochondrial biogenesis. In addition, liquiritigenin was found to possibly reverse the decrease in BCL2/BAX ratio induced by CP in live cultured renal tubule epithelial cells. Collectively, these results indicated that liquiritigenin could be used as a potential nephroprotective agent to protect against cisplatin-induced acute kidney injury in a NRF2-dependent manner by improving mitochondria function.Keywords:liquiritigenin;NRF2;cisplatin;SIRT3;mitochondrial biogenesis
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JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-17
·
IF 9.429
Gu Jiayi,Wang Xueling,Chen Yuming,Xu Ke,Yu Dehong,Wu Hao
Background Excessive accumulation of reactive oxygen species (ROS) has been documented as the crucial cellular mechanism of cisplatin-induced ototoxicity. However, numerous antioxidants have failed in clinical studies partly due to inefficient drug delivery to the cochlea. A drug delivery system is an attractive strategy to overcome this drawback.Methods and resultsIn the present study, we proposed the combination of antioxidant astaxanthin (ATX) and ROS-responsive/consuming nanoparticles (PPS-NP) to combat cisplatin-induced ototoxicity. ATX-PPS-NP were constructed by the self-assembly of an amphiphilic hyperbranched polyphosphoester containing thioketal units, which scavenged ROS and disintegrate to release the encapsulated ATX. The ROS-sensitivity was confirmed by 1H nuclear magnetic resonance spectroscopy, transmission electron microscopy and an H2O2 ON/OFF stimulated model. Enhanced release profiles stimulated by H2O2 were verified in artificial perilymph, the HEI-OC1 cell line and guinea pigs. In addition, ATX-PPS-NP efficiently inhibited cisplatin-induced HEI-OC1 cell cytotoxicity and apoptosis compared with ATX or PPS-NP alone, suggesting an enhanced effect of the combination of the natural active compound ATX and ROS-consuming PPS-NP. Moreover, ATX-PPS-NP attenuated outer hair cell losses in cultured organ of Corti. In guinea pigs, NiRe-PPS-NP verified a quick penetration across the round window membrane and ATX-PPS-NP showed protective effect on spiral ganglion neurons, which further attenuated cisplatin-induced moderate hearing loss. Further studies revealed that the protective mechanisms involved decreasing excessive ROS generation, reducing inflammatory chemokine (interleukin-6) release, increasing antioxidant glutathione expression and inhibiting the mitochondrial apoptotic pathway.Conclusion sThus, this ROS-responsive nanoparticle encapsulating ATX has favorable potential in the prevention of cisplatin-induced hearing loss.Graphical Abstract
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ACS Nano
·
2021
·
IF 15.881
Wei Zhang,Xiang-Fu Du,Ben Liu,Cairong Li,Jing Long,Mei-Xia Zhao,Zhenyu Yao,Xing-Jie Liang,Yuxiao Lai
Combinatorial cancer therapies based on nanomedicine have emerged as a promising strategy to achieve potentiated treatment efficiency. Herein, cisplatin (CDDP) prodrug (Pt-CD) and a mitochondria-targeted near-infrared (NIR) photosensitizer IR780 were combined to construct a multifunctional nanomedicine IR780@Pt NPs through a supramolecular self-assembly strategy. Targeted mitochondrial dysfunction of cancer cells was sufficiently induced under NIR laser irradiation through both photothermal and photodynamic effects, inhibiting the overactive mitochondrial energy pathways of cancer cells. The mitochondrial dysfunction significantly attenuated the crosstalk between mitochondria and nucleus via the cellular ATP energy chain, leading to obvious down-regulation of the key proteins of the nucleotide excision repair (NER) pathway. Thereby, the chemotherapeutic effect of CDDP could be significantly potentiated because of reduced DNA lesion repair capacity by ERCC1-XPF nuclease system. Moreover, IR780@Pt NPs exhibited excellent NIR fluorescence and photoacoustic (PA) imaging capacity for in vivo imaging-guided NIR laser treatment. Ultimately, the IR780@Pt NPs mediated combinatorial chemophototherapy achieved potentiated anticancer efficacy against cancer cells in vitro and tumor inhibition performance in vivo. Overall, this study highlighted the significance of nanomedicine mediated targeted induction of mitochondrial dysfunction to potentiate chemotherapy for efficient combinatorial cancer therapy.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-20
·
IF 10.435
Chen Yan,Fang Lei,Zhou Weixin,Chang Jinghan,Zhang Xiaojuan,He Chuanchuan,Chen Chen,Yan Ruicong,Yan Yakai,Lu Yao,Xu Chuanrui,Xiang Guangya
Background Hypoxic tumor microenvironment (TME) promotes tumor metastasis and drug resistance, leading to low efficiency of cancer chemotherapy. The development of targeted agents or multi-target therapies regulating hypoxic microenvironment is an important approach to overcome drug resistance and metastasis. Methods In this study, chitosan oligosaccharide (COS)-coated and sialic acid (SA) receptor-targeted nano-micelles were prepared using film dispersion method to co-deliver cisplatin (CDDP) and nitric oxide (NO) (denoted as CTP/CDDP). In addition, we explored the mechanisms by which NO reversed CDDP resistance as well as enhanced anti-metastatic efficacy in hypoxic cancer cells. Results Because of the different affinities of COS and SA to phenylboronic acid (PBA) under different pH regimes, CTP/CDDP micelles with intelligent targeting property increased cellular uptake of CDDP and enhanced cytotoxicity to tumors, but reduced systemic toxicity to normal organs or tissues. In addition, CTP/CDDP showed stimulus-responsive release in TME. In terms of anti-tumor mechanism, CTP/CDDP reduced CDDP efflux and inhibited epithelial-mesenchymal transition (EMT) process of tumor by down-regulating hypoxia-inducible factor-1α (HIF-1α), glutathione (GSH), multidrug resistance-associated protein 2 (MRP2) and matrix metalloproteinase 9 (MMP9) expression, thus reversing drug resistance and metastasis of hypoxic tumor cells. Conclusions The designed micelles significantly enhanced anti-tumor effects both in vitro and in vivo. These results suggested that CTP/CDDP represented a promising strategy to treat resistance and metastatic tumors. Graphic abstract
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JOURNAL OF CONTROLLED RELEASE
·
2021
·
IF 9.776
Yuanyuan Li,Jianming Xiong,Wenjing Guo,Yangye Jin,Wenjun Miao,Cong Wang,Hongman Zhang,Yi Hu,He Huang
Novel platforms for cisplatin delivery with a controllable manner and combinable with other treatment modality to achieve synergistic antitumor effect and inhibition metastasis for treatment of triple negative breast cancer (TNBC) are highly desirable. Herein, we report a black phosphorus (BP) nanosheets-based nano-assembly which consists of cisplatin, BP, polydopamine (PDA) and hyaluronic acid (HA), c isplatin/ B P/ P DA- H A (CBPH), for controlled delivery of cisplatin and inhibition tumor growth as well as lung metastasis of TNBC. For constructing CBPH, the surface of BP was dual modified by PDA and HA, resulting in enhanced stability, tumor target ability and photothermal efficiency of BP. Cisplatin was released in response both to internal and external stimuli existed in tumor microenvironment , including low pH, hydrogen peroxide and NIR light, as accompanied by decomposition of BP. In vitro experiments demonstrated CBPH-treated 4 T1 cells showed elevated intracellular content of Pt and Pt-DNA adduct, which was further improved when exposure to NIR light, leading to potent antitumor effect in a synergistic pattern. Anti-metastasis studies in 2D monolayers and 3D organoids revealed that CBPH plus NIR light treatment exhibited significantly decreased migration, invasion and regrowth ability of 4 T1 cells. Furthermore, TNBC-bearing mice with systemic administrate of CBPH showed enhanced tumor accumulation of cisplatin and light-triggered inhibition of tumor growth at primary site and lung metastasis, with alleviated toxicity. But CBPH is yet to be optimized for realizing smart cisplatin delivery in response to acidic and redox stimuli in vivo. Collectively, our study demonstrates that this novel BP-based nano-assembly with controllable tumor delivery of cisplatin and metastasis inhibition of breast cancer expand the use of BP in biomedicine field and hold great promise for further development.
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ONCOGENE
·
2023
·Vol. 42
·期 29
·2278-2293
·
IF 8
Chen Yihuan,Dai Xiaoshuo,Chen Wei,Qiao Yan,Bai Ruihua,Duan Xiaoxuan,Zhang Kai,Chen Xinhuan,Li Xin,Mo Saijun,Cao Wenbo,Li Xiang,Liu Kangdong,Dong Ziming,Lu Jing
Cisplatin (CDDP) is the first-line drug in the clinical treatment of esophageal squamous cell carcinoma (ESCC), which has severe nephrotoxicity. Diosmetin (DIOS) can protect kidney from oxidative damage, however, its function in ESCC is unknown. This study aims to explore the effect and mechanism of DIOS on ESCC and its combined effect with CDDP. Herein, we found that DIOS significantly inhibited the progression of ESCC in vitro and in vivo. Furthermore, the anti-tumor effect of DIOS was not statistically different from that of CDDP. Mechanically, transcriptomics revealed that DIOS inhibited the E2F2/RRM2 signaling pathway. The transcriptional regulation of RRM2 by E2F2 was verified by luciferase assay. Moreover, docking model, CETSA, pull-down assay and CDK2 inhibitor assay confirmed that DIOS directly targeted CDK2, leading to significant suppression of ESCC. Additionally, the patient-derived xenografts (PDX) model showed that the combination of DIOS and CDDP significantly inhibited the growth of ESCC. Importantly, the combined treatment with DIOS and CDDP significantly reduced the mRNA expression levels of kidney injury biomarkers KIM-1 and NGAL in renal tissue, as well as the levels of blood urea nitrogen, serum creatinine and blood uric acid compared to the single treatment with CDDP. In conclusion, DIOS could be an effective drug and a potential chemotherapeutic adjuvant for ESCC treatment. Furthermore, DIOS could reduce the nephrotoxicity of CDDP to some extent.
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CELL PROLIFERATION
·
2024
·
IF 5.9
Yuanchong Chen,Jiangshan Xu,Sirong Shi,Wenjuan Ma,Weitong Cui,Ran Yan,Yunfeng Lin
Since its discovery in 1978, cisplatin-based chemotherapy regimens have served a pivotal role in human cancer treatment, saving millions of lives. However, its high risk still poses a significant challenge for cisplatin-induced acute kidney injury (AKI), which occurs in 30% of cisplatin-treated patients. Unfortunately, no effective solution for preventing or managing this severe complication, which greatly impacts its clinical administration. Kidney is the main organ injured by cisplatin, and the injury is related to cisplatin-induced cell apoptosis and DNA injury. Therefore, to achieve the safe use of cisplatin in tumour treatment, the key lies in identifying a kidney treatment that can effectively minimize cisplatin nephrotoxicity. Here, we successfully synthesized and applied a DNA-nanostructure complex, named TFG, which contains tetrahedral framework nucleic acids (tFNAs) and FG-4592, a novel Hif-1α inducer. As cargo, TFG is composed entirely of DNA strands. It possesses low nephrotoxicity and renal aggregation properties while FG-4592 is able to relieve renal injury by downregulating the apoptosis signal pathways. And it can relieve cisplatin-induced renal injury when taken cisplatin treatment. This work aims to enhance chemotherapy protection in tumour patients by using TFG, a DNA-based nanomedicines to kidney. This work has the potential to revolutionize the treatment of renal diseases, particularly drug-induced kidney injury, leading to improved clinical outcomes.
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