DRUG DELIVERY
·
2018
·
IF 3.095
Jincheng Yang,Qingzhi Lv,Wei Wei,Zhengtao Yang,Jiajun Dong,Ruoshi Zhang,Qiming Kan,Zhonggui He,Youjun Xu
The efficacy of traditional chemotherapy often suffers from rapid clearance and off-target toxicity. Drug delivery systems and controlled release are applied to improve the therapeutic efficiencies of small-molecule drugs. In this work, two novel oxidative/reductive (Ox/Re) -sensitive and one non-sensitive Paclitaxel (PTX) prodrugs were synthesized with a maleimide group, which rapidly conjugates with albumin in vivo. Albumin serves as a good vehicle to deliver more prodrug to tumors due to the enhanced permeation and retention (EPR) effect. PTX was then released from the prodrugs in glutathione(GSH)/ reactive oxygen species(ROS)-rich tumor microenvironments. This bioresponsive prodrug strategy demonstrates potent chemotherapeutic efficiency in vivo and may be utilized in clinical cancer therapy.
研究领域:
药物化学
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肿瘤学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
CURRENT CANCER DRUG TARGETS
·
2024
·Vol. 25
·期 3
·294-305
·
IF 2.3
Yiping Zheng,Jianfeng Cai,Qiuhong Ji,Luanmei Liu,Kaijun Liao,Lie Dong,Jie Gao,Yinghui Huang
BackgroundLung cancer remains a major global health threat due to its complex microenvironment, particularly the role of neutrophils, which are crucial for tumor development and immune evasion mechanisms. This study aimed to delve into the impact of lung cancer cell-conditioned media on neutrophil functions and their potential implications for lung cancer progression.MethodsEmploying in vitro experimental models, this study has analyzed the effects of lung cancer cell-conditioned media on neutrophil IL-8 and IFN-γ secretion, apoptosis, PD-L1 expression, and T-cell proliferation by using techniques, such as ELISA, flow cytometry, immunofluorescence, and CFSE proliferation assay. The roles of IL-8/PD-L1 in regulating neutrophil functions were further explored using inhibitors for IL-8 and PD-L1.ResultsLung cancer cell lines were found to secrete higher levels of IL-8 compared to normal lung epithelial cells. The conditioned media from lung cancer cells significantly reduced apoptosis in neutrophils, increased PD-L1 expression, and suppressed T-cell proliferation and IFN-γ secretion. These effects were partially reversed in the presence of IL-8 inhibitors in Tumor Tissue Culture Supernatants (TTCS), while being further enhanced by IL-8. Both apoptosis and PD-L1 expression in neutrophils demonstrated dose-dependency to TTCS. Additionally, CFSE proliferation assay results further confirmed the inhibitory effect of lung cancer cell-conditioned media on T-cell proliferation.ConclusionThis study has revealed lung cancer cell-conditioned media to modulate neutrophil functions through regulating factors, such as IL-8, thereby affecting immune regulation and tumor progression in the lung cancer microenvironment.
研究领域:
肿瘤学
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免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2024
·
IF 3.7
Hao Xu,Ning Ning Guo,Chen Ying Zhu,Lin Yan Ye,Xing Yi Yan,Yong Qin Liu,Ze Yan Zhang,Guangji Zhang,Liaqat Hussain
Diterpenoid tanshinones (DTs) are a bioactive fraction extracted from Salvia miltiorrhiza. High-performance liquid chromatography analysis revealed the presence of four compounds, namely, tanshinone IIA, tanshinone I, cryptotanshinone, and dihydrotanshinone. In this study, we aimed to propose a possible mechanism for the anti-lung cancer effect of DT. To do so, we utilized a lung cancer nude mice model and a lung cancer cell line (PC9) to investigate the effect of DT on lung cancer. We employed immunohistochemistry, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, and immunofluorescence to analyze the pharmacological role of DT in the inhibition of lung cancer growth. The results showed that DT inhibited tumor growth, induced apoptosis in the nude mice model, and reduced inflammatory cell infiltration. Additionally, DT inhibited PC9 lung cancer cells, growth, proliferation, and migration. The mechanism of action of DT involves not only directly inhibiting cell proliferation and migration but also improving the tumor microenvironment. DT significantly increased the expression of important intestinal gap junction proteins, such as zonula occludens 1 (ZO-1) and occludin I. This upregulation contributes to the reinforcement of the intestinal mucosal barrier, thereby reducing the paracellular transport of lipopolysaccharides (LPS) through the intestine. Consequently, the decreased LPS levels lead to the inhibition of NF-κB expression and downregulation of macrophage polarization, as indicated by the decreased expression of CD68. In conclusion, this study has confirmed that DT has anti-lung cancer properties by improving the inflammatory tumor microenvironment via regulating macrophage polarization and inhibiting LPS-associated immune response. These results provide new insights into the mechanism of DT action against lung cancer.
研究领域:
肿瘤学
·
药理学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Fan Wu,Yu Qian,Chenglong Ge,Yang Zhou,Jing Yan,Xudong Li,Xun Liu,Yuheng Lei,Ziyin Zhao,Yuansong Wei,Junliang Zhu,Lichen Yin,Shanzhou Duan
The anti-tumor efficacy of radiotherapy (RT) is limited by the hypoxic and immunosuppressive tumor microenvironment (TME), which leads to RT resistance and failure in eradicating distant metastatic lesions. Herein, we developed a fluorinated nanosensitizer that could deliver both oxygen (O 2 ) and ADAR1 siRNA into tumor cells to reinforce RT by alleviating hypoxia and immunosuppression. Fluorinated poly(β-amino ester) (fPBAE) was designed to complex ADAR1 siRNA (siADAR1) via electrostatic attraction and load O 2 due to the O 2 -dissolving capacity of fluoroalkyls. The formed nanocomplexes (NCs) facilitated robust cytosolic delivery into cancer cells after intratumoral injection, enabling efficient ADAR1 silencing to promote IFN-β release and enhance DC maturation and T cell infiltration. At the meantime, O 2 was released to alleviate tumoral hypoxia. As thus, NCs significantly enhanced the anti-tumor efficacy of RT and when further coupled with programmed death ligand-1 antibody, they effectively restrained the growth of both treated primary tumors and untreated distant tumors by eliciting robust systemic immune response. This study therefore reports an enlightened strategy for remodeling the immunosuppressive TME and sensitizing radio-immunotherapy. Statement of significance The hypoxic and immunosuppressive tumor microenvironment (TME) greatly limits the anti-tumor efficacy of radiotherapy (RT). To address this critical issue, a nano-sensitizer based on fluorinated poly(β-amino ester) (fPBAE) is herein developed to mediate efficient co-delivery of oxygen (O₂) and ADAR1 siRNA into tumor cells. ADAR1 silencing promotes DC maturation and T cell infiltration to reverse immunosuppression while the released O₂ sensitizes RT. Thus, the nano-sensitizer remarkably enhances the anti-tumor efficacy of RT and elicits robust systemic immune response to eradicate primary and distant tumors when further coupled with PD-L1 antibody.
研究领域:
肿瘤学
·
分子生物学
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纳米医学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2025
·
IF 5.5
Tianhui Liu,Qingshuang Wang,Wenxin Geng,Xue Jiang,Changshun Lu,Zhe Zhang,Xiangru Feng
The cancer-associated fibroblasts (CAFs) in tumor stroma present substantial barriers to drug penetration, resulting in tumor resistance and progression. One promising strategy is to reprogram CAFs into a quiescent state, which necessitates novel approaches. Our study introduces a sequential treatment strategy using chitosan thermosensitive hydrogels loaded with α-Mangostin (α-M), a small molecule drug with antifibrotic properties, aimed at reprogramming CAFs within the breast cancer tumor microenvironment (TME). We developed glutathione (GSH)-responsive nanoparticles (NPc) that carry the chemotherapeutic drug doxorubicin (DOX). Treatment with α-M results in the downregulation of CAF-specific biomarkers and a remodeled TME, which improves the penetration of NPc/DOX deep into the tumor tissue. This strategy holds great promise in enhancing cancer therapeutic outcomes in tumors rich in CAFs, particularly in the case of breast cancer.
研究领域:
肿瘤学
·
药剂学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Changmei Chen,Qinghua Yu,Lulu Wang,Rongchun Yi,Siying Huang,Xiangshu Cheng,Tao Deng
Chemotherapy combined with immunotherapy represents a promising combination therapy for tumor treatment. The low targeting of chemotherapeutic drugs and the potential immune-related adverse events (irAEs) of immune adjuvants hinder the realization of combination therapy. To solve these problems, we propose to further conjugate immunoadjuvant OVA using boric acid (BA) modified drug-carrying carbon dots, and develop a multifunctional nano drug delivery system for hierarchical targeting of focal sites (RCD@DOX/BA-O). From a mechanistic perspective, based on the pKa of BA, RCD@DOX/BA can couple OVA (1, 3-n-diol) under alkaline conditions and release OVA under tumor microenvironment, which could prevent the occurrence of irAEs. Furthermore, the exposed BA was able to combine with sialic acid (SA) (1, 2-n-diol) under the acidic tumor microenvironment, thereby enhancing its tumor-targeting capabilities. Specially, the immune effect (tumor-associated macrophages (TAMs) to M1) of OVA and the tumor targeted enhancement was verified by cell experiments. The treatment effect of RCD@DOX/BA-O was further proved on animal level. Overall, our finding suggests that the synthesized RCD@DOX/BA-O enabling synergistic chemotherapy and immunotherapy through hierarchical targeting to enhance anti-tumor efficacy and reduce irAEs. It is of great significance for targeted immunotherapy and improving the therapeutic effect of tumor.
研究领域:
纳米医学
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肿瘤学
·
免疫学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·
IF 12.6
Bo Deng,Youpeng Kong,Yingying Ma,Yijie Zhan,Yitong Sun,Rudan Wang,Pengyu Huang,Lanxia Liu
Despite significant advancements in oncology, cancer remains a leading global health burden, necessitating innovative therapeutic strategies. Here, we present a novel carrier-free tumor-targeted nanomedicine system (DPA NPs) for tumor-targeted chemoimmunotherapy, formed by self-assembly of a conjugate synthesized with doxorubicin (DOX), tumor-homing peptide iRGD, matrix metalloproteinase 2 enzyme responsive peptide (MMP2), and adjuvant monophosphoryl lipid A (MPLA). The results demonstrated that DPA NPs exhibited a stable unique 3D nanostructure with tumor microenvironment (TME)-responsive properties. DPA NPs could efficiently deliver DOX to tumor cells, inducing immunogenic cell death (ICD) and simultaneously triggering tumor specific immune response. Meanwhile, MPLA amplified the anti-tumor immunity, significantly inhibiting tumor growth and metastasis. When combined with immune checkpoint inhibitors (ICIs), DPA NPs further enhanced the therapeutic outcomes in a B16 melanoma model, demonstrating remarkable suppression of tumor growth, metastasis inhibition and recurrence prevention. Mechanistic investigations across multiple biological hierarchies conclusively further confirmed the synergistic therapeutic effect. This study demonstrated that DPA NPs provide a precise, multifunctional nanoplatform for tumor-targeted combination therapy, highlighting their potential for clinical translation in cancer treatment.
研究领域:
肿瘤学
·
生物医学工程
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Qianqian Wang,Xin Yuan,Cuijuan Liu,Ying Huang,Lin Li,Yimin Zhu
CAR-T cell therapy has been proven to be effective on hematological tumors, although graft-versus-host disease and cytokine release syndrome(CRS) limit its application to a certain extent. However, CAR-T therapy for solid tumors met challenges, among which the lack of tumor-specific antigens (TSA) and immunosuppressive tumor microenvironment (TME) are the most important factors. CAR-NK could be a good alternative to CAR-T in some ways since they can induce mild CRS and are independent of HLA-matching, but the efficacy of CAR-NKs remains limited in solid tumors. CAR cells armed with multiple tumor targeting molecules may obtain higher therapeutic efficacy against solid tumors. Due to large molecular weight, multivalent scFvs cannot be displayed efficiently on T cells and the high affinity of scFv to the target makes it easy to cause on-target, off-tumor(OTOT) toxicity. Peptides with low molecular weight and slightly lower affinity than scFvs allow immune cells to display multiple peptides to increase killing ability and reduce OTOT toxicity. In our study, peptide-based CAR-NK cells were designed to solve the dilemma of CAR-T in solid tumors. Firstly, the peptide-based CAR-NK92MI cells with A1 peptide were constructed and their inhibitory effects on the growth of A549 tumor cells were identified. Secondly, the tri-specific CAR-NK92MI cells with peptides that simultaneously targeted PD-L1, EGFR and VEGFR2 were developed for the combinatory therapy. Tri-specific CAR-NK92MI exhibited comparable killing activities to scFv-based CAR-NK92MI. Moreover, peptide-based CAR NK92MI mitigated OTOT toxicity. Our study implied that peptide-based CAR-NKs could behave as promising tools in solid tumor
研究领域:
免疫学
·
肿瘤学
·
细胞治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 6
·2313-2321
·
IF 6.843
Yuchu He,Cong Cong,Shuxian Zhao,Zhuo Li,Desong Wang,Jianmin Gu,Lanxiang Liu,Dawei Gao
The gaseous microenvironment (GME) of tumors is rapidly becoming a new concern for nanotechnology-mediated oncotherapy. Here, we constructed a tumor/near-infrared (NIR) light-responsive nanoplatform to generate O2 and NO for remodeling the GME of tumors and phototherapy. The biocompatible and pyrolytic polydopamine was used to load indocyanine green, NONOate, and MnO2 NPs as a nanoenzyme (PINM). Then, HA was modified on the PINM to form the final nanoplatform (PINMH). PINMH can target tumors favorably due to the modification of HA. Under the NIR light irradiation, PINM converts the light and O2 to hyperpyrexia (58.5 °C) and cytotoxic 1O2. MnO2 NPs catalyze the H2O2 overexpressed in tumors to O2, which increases the amount of 1O2. Moreover, NONOate decomposes to NO (100 μM) under hyperpyrexia, thus leading to the gas therapy. The results verified that the responsive nanoplatform with precise gaseous regulation and phototherapy exhibited a superior anti-tumor effect (V/V0 = 1.2) and biosafety. In addition, PINMH can be tracked in real-time via magnetic resonance imaging. In this study, an intelligent nano-platform integrated with diagnosis and treatment was developed, which used the phototherapy technology to reshape GME and achieve good anti-tumor effects, aiming to provide an innovative and reasonable strategy for the development of tumor treatment.
研究领域:
肿瘤学
·
纳米医学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2013
·
IF 7.604
Wei-Hai Chen,Xiao-Ding Xu,Hui-Zhen Jia,Qi Lei,Guo-Feng Luo,Si-Xue Cheng,Ren-Xi Zhuo,Xian-Zheng Zhang
A novel strategy to construct a therapeutic system based on functionalized AuNPs which can specifically respond to tumor microenvironment was reported. In the therapeutic system, doxorubicin was conjugated to AuNPs via thiol–Au bond by using a peptide substrate, CPLGLAGG, which can be specifically cleaved by the protease. In vivo study shows that after injection of the functionalized AuNPs to the tumor-bearing mice, the over-expressed protease of MMP-2 in tumor tissue and intracellular GSH can lead to the rapid release of the anti-tumor drug (doxorubicin) from the functionalized AuNPs to inhibit tumor growth and realize fluorescently imaging simultaneously. The functionalized AuNPs with tumor-triggered drug release property can further improve the efficacy and reduce side effects significantly.
研究领域:
纳米医学
·
肿瘤学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2022
·
IF 9.965
Rui Zhang,Changlin Liu,Ruoxi Zhao,Yaqian Du,Dan Yang,He Ding,Guixin Yang,Shili Gai,Fei He,Piaoping Yang
There is an urgent need to develop photosensitive nanoenzymes with better phototherapeutic efficiency through simple processes. By exploiting semiconductor catalysis and defect chemistry principles, herein, a MnMoO x composite semiconductor nanoenzyme was developed to achieve a fully integrated theranostic nanoenzyme for highly efficient photo/chemo-enzyme-dynamic eradication of deep tumors. Relative to iron oxides, manganese oxides offer ideal catalytic performance under near-neutral conditions, which helps to broaden the suitable pH range of the MnMoO x nanoenzyme for antitumor therapy. Furthermore, with the assistance of glutathione depletion, Mn 4+ /Mo 6+ was successfully converted to Mn 2+ /Mo 5+ , inhibiting the scavenging of reactive oxygen species (ROS) and promoting cycling. Therefore, MnMoO x has favorable catalase (CAT)-like activity and oxidase (OXD)-like activity in the tumor microenvironment (TME) for promoting the “H 2 O 2 O 2 O 2 − ” and “H 2 O 2 OH” cascade reactions. The abundant oxygen vacancy defects also promote the surface plasmon resonance (SPR) effect in the second near-infrared (NIR-II) window of MnMoO x , which significantly enhanced its photothermal therapy (PTT) effect and catalytic activity. In detail, ROS production was significantly enhanced due to the adsorption of water and oxygen molecules by the rich oxygen vacancies of MnMoO x . MnMoO x also exhibited excellent multi-modal imaging activity (including computed tomography (CT), magnetic resonance imaging (MRI), and photoacoustic (PA)), which can be exploited to better guide the administration of medication.
研究领域:
生物医学工程
·
纳米医学
·
肿瘤治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Sichen Li,Difei Zhang,Yi Li,Jingjing Zhou,Jinghua Chen,Yan Zhang
Cisplatin (CDDP) as a first-line chemotherapy drug has long suffered drawbacks of severe side effects and poor pharmacokinetics. Thus, various nano-carriers of complex architectures and multi-step modifications have been developed to overcome these challenges, but a simple delivery system with integrated multi-functions is still in demand. Herein, we synthesized a new type of glyco-based triple hydrophilic block copolymers for the delivery of CDDP and thereof cancer therapy. The incorporated glucuronic acid part is complexed with CDDP with high entrapment efficiency, while providing pH-responsive release in the acidic tumor microenvironment. The galactose segment is implanted for liver-targeting effect, which can also significantly lower the side effects of CDDP. As a result, the CDDP-loaded nanoparticle PGG2/Pt showed selectively faster endocytosis rates into HepG2 cells in vitro, with the calculated IC 50 value even comparable to that of free CDDP. The in vivo experiments on a HepG2-bearing mouse model, PGG2/Pt showed excellent anti-tumor activity and enhanced drug accumulation on tumor, together with much lowered nephrotoxicity, hepatotoxicity, and splenic toxicity. This work provides a new strategy for CDDP delivery with higher loading efficiency as well as biosafety.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）