International Journal of Nanomedicine
·
2022
·
IF 7.033
Shuo Qi,Gongyuan Liu,Jiangbo Chen,Peng Cao,Xiaohua Lei,Chengming Ding,Guodong Chen,Yachao Zhang,Lidai Wang
Background Effective theranostic of hepatocellular carcinoma (HCC) in an early-stage is imminently demanded to improve its poor prognosis. Combination of the near-infrared (NIR) photoacoustic imaging (PAI) and fluorescence imaging (FLI) can provide high temporospatial resolution, outstanding optical contrast, and deep penetration and thus is promising for accurate and sensitive HCC diagnosis. Methods A versatile CXCR4-targeted Indocyanine green (ICG)/Platinum (Pt)-doped polydopamine melanin-mimic nanoparticle (designated ICG/Pt@PDA-CXCR4, referred to as IPP-c) is synthesized as an HCC-specific contrast agent for high-resolution precise diagnostic PAI/FLI and optical imaging-guided targeted photothermal therapy (PTT)/photodynamic therapy (PDT) of orthotopic small hepatocellular carcinoma (SHCC). Results The multifunctional targeted nanoparticle yields superior HCC specificity, high imaging contrast in both PAI and FLI, good stability, reliable biocompatibility, effective singlet oxygen generation and superior photothermal conversion efficiency (PCE, 58.7%) upon 808-nm laser irradiation. The targeting ability of IPP-c was validated in in vitro experiments on selectively killing the CXCR4-overexpressing HCC cells. Moreover, we test the efficient dual-modal optical precision diagnosis properties of IPP-c via in vivo experiments on targeted particle accumulation in an early-stage SHCC mouse model (tumor diameter about 1.2 mm). Then, under the guidance of real-time optical imaging, effective and mini-invasive PTT/PDT of orthotopic SHCCs were demonstrated without damaging adjacent liver tissues or other major organs. Conclusion This study presented a multifunctional CXCR4-targeted nanoparticle to conduct effective and mini-invasive phototherapeutics of orthotopic SHCCs via the real-time quantitative guidance by optical imaging, which provided a new perception for building a versatile targeted nanoplatform for phototheranostics of early-stage HCC.
研究领域:
医学影像学
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肿瘤学
·
纳米医学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·
IF 12.6
Bai Lu,Tan Ya-Nan,Zhang Li-Fen,Luo Min,Luo Jie,Yang Yu-Ma,Liu Yun-Zhi,Ho-Fun Lee Victor,Feng-Ming Kong Spring,Guan Xin-Yuan
Background Cell membrane-camouflaged nanoparticles (NPs) have attracted increasing attention for cancer-targeted drug delivery, but their clinical translation faces critical challenges due to the biosafety concerns and scalability issues. Dermal fibroblasts are an abundant, clinically accessible membrane source, and genetic programmability offers a route to active homing. Results We engineered fibroblast membrane nanovesicles from dermal fibroblasts overexpressing CXCR4 to actively home toward CXCL12-enriched tumor microenvironments. These CXCR4-engineered membrane nanovesicles demonstrated tumor-selective accumulation in multiple preclinical models with high CXCL12 secretion. The near-infrared (NIR) photosensitizer IR780 and the ferroptosis inducer RSL3 were co-loaded to form FbM@IR/RSL3 NPs for photothermal-controlled ferroptosis therapy. Upon NIR irradiation, FbM@IR/RSL3 NPs generated localized photothermal heating and simultaneously triggered RSL3 release. The combination of glutathione peroxidase 4 (GPX4) inhibition and iron-catalyzed lipid peroxidation amplified ferroptotic tumor cell death. In vivo studies reveal enhanced tumor suppression across heterogeneous carcinoma models compared to monotherapy approaches, with systemic biocompatibility confirmed by comprehensive hematological and histopathological analyses. Conclusions Fibroblast membrane engineering, combined with chemokine-gradient navigation and photothermally controlled therapeutic activation, represents the translational potential of nanomedicine in clinical by developing precision nanomedicines that coordinate biological recognition with stimulus-responsive bioactivity. Graphical
研究领域:
肿瘤学
·
纳米医学
·
药物递送
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分子靶向治疗
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转化医学
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生物材料
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细胞膜工程
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2022
·Vol. 10
·期 10
·2650-2664
·
IF 7.59
Aftab Ullah,Gang Chen,Zhang Yibang,Abid Hussain,Muhammad Shafiq,Faisal Raza,Daojun Liu,Kaikai Wang,Jin Cao,Xueyong Qi
Liver fibrosis results from excessive extracellular matrix accumulation due to injury and leads to cirrhosis, cancer, and death. Herein, we propose a chemokine receptor 4 (CXCR4)-targeted combination (CTC) liposomal therapy to treat carbon tetrachloride (CCl4)-induced liver fibrosis in a mouse model. This study aims to combine small molecules such as pirfenidone and AMD3100 in a single nanoplatform to investigate their synergistic antifibrotic effects in a setting of CCl4-induced liver fibrosis. CTC liposomes (CTC lipo) were prepared using the thin-film hydration method. CTC lipo exhibited a spherical shape, and the particle size was recorded at the nanoscale which confirms its appropriateness for in vitro and in vivo applications. CTC lipo had good storage and serum stability. The entrapped drugs in CTC lipo showed reduced toxicity at higher concentrations. CTC lipo displayed CXCR4 mediated cell uptake and were internalized by caveolae-mediated endocytosis. CTC lipo showed CXCR4 targeting and stromal cell-derived factor 1α (SDF1-α)/CXCR4 axis blocking activity. CTC lipo reduced the elevated serum aspartate aminotransferase (AST), alanine transaminase (ALT), and hydroxyproline (HYP) levels. The histological studies showed improved liver architecture and reduced collagen deposition after treatment. Transforming growth factor β (TGFβ), alpha-smooth muscle actin (α-SMA), and collagen I were elevated by CCl4 in comparison with the Sham. Upon CTC liposomal treatment, the quantitative score for the elevated fibrotic proteins such as TGFβ, α-SMA, and collagen I was normalized. CTC lipo displayed significant downregulation of the upregulated TGFβ, α-SMA, collagen I, and P-p38 expressions at the molecular level. The CXCR4 targeted liposomes showed prolonged biodistribution at 24 h. Our findings indicated that CTC lipo might be an alternative antifibrotic therapy that may offer new access to research and development. In a nutshell, the present study suggests that systemic administration of CTC lipo has efficient antifibrotic potential and deserves to be investigated for further clinical applications.
研究领域:
药理学
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纳米技术
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肝病学
·
分子生物学
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DOI
PubMed
高影响因子
Frontiers in Immunology
·
2020
·
IF 5.085
Lu Wei-Jia,Zhou Li,Gao Fan-Xiang,Zhou Yu-Lin,Li Zhi,Zhang Xiao-Juan,Wang Yang,Gui Jian-Fang
Chemokine receptor cxcr4 and its ligand cxcl12 have evolved two paralogs in the teleost lineage. In this study, we have identified four duplicated cxcr4 and cxcl12 genes from hexaploid gibel carp, Carassius gibelio, respectively. Cgcxcr4bs and Cgcxcl12as were dynamically and differentially expressed in immune-related tissues, and significantly up-regulated in head kidney and spleen after crucian carp herpesvirus (CaHV) infection. Blocking Cxcr4/Cxcl12 axis by injecting AMD3100 brought more severe bleeding symptom and lower survival rate in CaHV-infected fish. AMD3100 treatment also suppressed the up-regulation of key antiviral genes in head kidney and spleen, and resulted in more acute replication of CaHV in vivo. Consistently, the similar suppression of up-regulated expression of key antiviral genes were also observed in CAB cells treated by AMD3100 after poly(I:C) stimulation. Finally, MAPK3 and JAK/STAT were identified as the possible pathways that CgCxcr4s and CgCxcl12s participate in to promote the antiviral response in vitro.
研究领域:
分子生物学
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免疫学
·
病毒学
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鱼类遗传学
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DOI
PubMed
高影响因子
Advanced Science
·
2026
·
IF 14.1
Lixia Feng,Simei Zhao,Zheng Wei,Wenwen Wang,Feiquan Ying,Lin Huang,Mengna Zhu,Mengqing Chen,Qiang Yang,Si Sun,Dawei Jiang,Lingling Gao,Jing Cai
Therapy targeting cancer stem cells (CSCs) has been proposed as a promising strategy to reduce chemoresistance and relapse risks in ovarian cancer (OC) patients. However, the lack of targetable markers impedes research progress. Here, we demonstrate that CXC motif chemokine receptor 4 (CXCR4) may be a targetable functional marker of ovarian CSCs and propose a new translational model incorporating targeted imaging and CXCR4 blockade in CXCR4 + tumors. Expression profile analysis of chemoresistant CSC-like ovarian cancer cells highlighted that CXCR4 functions as a potential stemness marker. CXCR4 + ovarian cancer cells exhibited high self-renewal capacity in vitro and in vivo, and an association with chemoresistance. CXCR4 inhibitor AMD3100 significantly impaired the self-renewal ability of CSC-like ovarian cancer cells and enhanced their sensitivity to cisplatin. CXCR4-targeted [ 68 Ga]Ga-Pentixafor was highly specific in delineating CXCR4-high cell line-derived xenografts and patient-derived xenografts (PDXs) via positron emission tomography (PET) imaging, with precise tumor-targeting and persistent retention. A combination of AMD3100 and CDDP exerted an excellent antitumor effect in CXCR4-high PDXs, but not in CXCR4-low PDXs. These results suggest that CXCR4 may represent a functional CSC marker associated with chemoresistance. Moreover, [ 68 Ga]Ga-Pentixafor PET imaging can guide decision-making for AMD3100 therapy, paving the way for further clinical translation.
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DOI
PubMed
高影响因子
Nanomaterials
·
2022
·Vol. 12
·期 10
·1711
·
IF 5.719
Fan Wang,Yuqi Jiang,Luhai Wang,Yi Chen,Yu Zhang,Ming Ma
Drug resistance and relapse lead to high mortality in acute myeloid leukemia, and studies have shown that CXCR4 overexpression is highly correlated with poor prognosis and drug resistance in leukemia cells. Isolation and detection of AML cells with CXCR4 overexpression will be crucial to the treatment of AML. In this paper, magnetic nanoparticles were firstly prepared successfully by high-temperature thermal decomposition method, and then characterized by TEM, VSM and DLS. Subsequently CXCR4-targeted magnetic fluorescent nanoprobes conjugated with antibody 12G5 were constructed by stepwise coupling. In cell experiments, the obtained probes demonstrated excellent targeting efficacy to CXCR4 overexpressed AML cells HL-60. In addition, HL-60 cells labelled with the magnetic probes can be magnetic isolated successfully in one microfluidics chip, with efficiency of 82.92 ± 7.03%. Overall, this method utilizes the superiority of superparamagnetic nanomaterials and microfluidic technology to achieve the enrichment and capture of drug-resistant cells in a microfluidic chip, providing a new idea for the isolation and detective of drug-resistant acute myeloid leukemia cells.Keywords:acute myeloid leukemia;magnetic nanoparticles;nanoprobe;magnetic isolation;microfluidic chip
研究领域:
肿瘤学
·
纳米技术
·
血液学
·
分子生物学
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DOI
PubMed
高影响因子
Theranostics
·
2019
·
IF 8.063
Yaodong Chen,Pengfei Liu,Peng Sun,Jian Jiang,Yuanbo Zhu,Tianxiu Dong,Yingzhe Cui,Yuan Tian,Tingting An,Jiuwei Zhang,Zizhuo Li,Xiuhua Yang
Glioblastoma multiforme (GBM) has been considered the most aggressive glioma type. Temozolomide (TMZ) is the main first-line chemotherapeutic agent for GBM. Decreased mutS homolog 6 (MSH6) expression is clinically recognized as one of the principal reasons for GBM resistance to TMZ. However, the specific functions of MSH6 in GBM, in addition to its role in mismatch repair, remain unknown. Methods: Bioinformatics were employed to analyze MSH6 mRNA and protein levels in GBM clinical samples and to predict the potential cancer-promoting functions and mechanisms of MSH6. MSH6 levels were silenced or overexpressed in GBM cells to assess its functional effects in vitro and in vivo . Western blot, qRT-PCR, and immunofluorescence assays were used to explore the relevant molecular mechanisms. Cu 2 (OH)PO 4 @PAA nanoparticles were fabricated through a hydrothermal method. Their MRI and photothermal effects as well as their effect on restraining the MSH6-CXCR4-TGFB1 feedback loop were investigated in vitro and in vivo . Results: We demonstrated that MSH6 is an overexpressed oncogene in human GBM tissues. MSH6, CXCR4 and TGFB1 formed a triangular MSH6-CXCR4-TGFB1 feedback loop that accelerated gliomagenesis, proliferation (G1 phase), migration and invasion (epithelial-to-mesenchymal transition; EMT), stemness, angiogenesis and antiapoptotic effects by regulating the p-STAT3/Slug and p-Smad2/3/ZEB2 signaling pathways in GBM. In addition, the MSH6-CXCR4-TGFB1 feedback loop was a vital marker of GBM, making it a promising therapeutic target. Notably, photothermal therapy (PTT) mediated by Cu 2 (OH)PO 4 @PAA + near infrared (NIR) irradiation showed outstanding therapeutic effects, which might be associated with a repressed MSH6-CXCR4-TGFB1 feedback loop and its downstream factors in GBM. Simultaneously, the prominent MR imaging (T1WI) ability of Cu 2 (OH)PO 4 @PAA could provide visual guidance for PTT. Conclusions: Our findings indicate that the oncogenic MSH6-CXCR4-TGFB1 feedback loop is a novel therapeutic target for GBM and that PTT is associated with the inhibition of the MSH6-CXCR4-TGFB1 loop.
研究领域:
肿瘤学
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生物医学工程
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分子生物学
·
癌症治疗
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纳米技术
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DOI
PubMed
高影响因子
Biomedicines
·
2025
·Vol. 13
·期 2
·486
·
IF 3.9
Chunli Zhu,Yiheng Cheng,Lei Yang,Yifu Lyu,Jingjing Li,Pengbo Zhao,Ying Zhu,Xiaofei Xin,Lifang Yin
Background and Objectives: As a key mechanism of metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis, inflammation triggered by chronic liver injury and immune cells with macrophages enables MASLD to progress to an advanced stage with irreversible processes such as fibrosis, cell necrosis, and cancer in the liver. The complexity of MASLD, including crosstalk between multiple organs and the liver, makes developing a new drug for MASLD challenging, especially in single-drug therapy. It was reported that upregulation of Notch1 is closely associated with the function of pro-inflammatory macrophages. To leverage this signaling pathway in treating MASLD, we developed a combination therapy.Materials and Methods: We chose Notch1 siRNA (siNotch1) to block the Notch pathway so that phenotypic regulation and functional recovery can be achieved in macrophages, combining with small molecule drug AMD3100. AMD3100 can cut off the migration of inflammatory cells to the liver to impede the development of inflammation and inhibit the CXCL12/CXCR4 biological axis in liver fibrosis to protect against the activation of HSCs. Then, we investigated the efficacy of the combination therapy on resolving inflammation and MASLD.Results: We demonstrated that in liver cells, siNotch1 combined with AMD3100 not only directly modulated macrophages by downregulating multiple pathways downstream of Notch, exerting anti-inflammatory, anti-migration, and switch of macrophage phenotype, but also modulated macrophage phenotypes through inhibiting NET release. The restored macrophages further regulate HSC and neutrophils. In in vivo pharmacodynamic studies, combination therapy exhibits a superior therapeutical effect over monotherapy in MASLD models.Conclusions: These results constitute an siRNA therapeutical approach combined with a small molecule drug against inflammation and liver injury in MASLD, offering a promising therapeutic intervention for MASLD.
研究领域:
医学
·
药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Airu Huang,Ling Ji,Yilong Huang,Qian Yu,Yufeng Li
MicroRNAs (miRNAs) are important modulators in the evolvement and progression of neuropathic pain (NP). According to reports, miR-185-5p contributes to various diseases and inflammatory responses. However, it is not clear whether miR-185-5p mediates neuroinflammation and NP following chronic constrictive injury (CCI). The CCI model was constructed in rats to induce NP. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were employed to evaluate pain threshold in CCI rats. The expression of miR-185-5p, GFAP, Iba1, Caspase-3-positive cells, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-labeled apoptotic neurons, inflammatory mediators, including interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) in lumbar portion (L4-L6) of CCI rats were determined. Furthermore, the targets of miR-185-5p were predicted by the Starbase, and the binding association between miR-185-5p and MyD88, miR-185-5p and CXCR4 was verified by the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. As shown by the data, miR-185-5p was distinctly reduced in L4-L6 spinal cord tissues of rats after CCI. Up-regulating miR-185-5p alleviated mechanical and thermal hyperalgesia, inactivated microglia and astrocytes accumulation, and abated the contents of IL-1β, IL-6 and TNF-α in L4-L6 spinal cord tissues of CCI rats. Bioinformatics analysis suggested that MyD88 and CXCR4 were potential target genes of miR-185-5p. Increasing miR-185-5p expression notably impeded the expression of MyD88, CXCR4 and NLRP3 inflammasome in BV2 microglia, while attenuating miR-185-5p expression exerted the opposite effects. Notably, down-regulating MyD88 and CXCR4 significantly enhanced the miR-185-5p-mediated anti-inflammatory effects, and reversed miR-185-5p inhibitor-mediated proinflammatory effects. Additionally, up-regulating miR-185-5p repressed BV2-induced neuronal apoptosis and increased neuronal viability. In conclusion, this study suggested that miR-185-5p chokes CCI-induced NP and neuroinflammation by targeting MyD88 and CXCR4, indicating that miR-186-5p is an underlying therapeutic target for NP.
研究领域:
神经科学
·
分子生物学
·
药理学
·
疼痛研究
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DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2026
·
IF 14.6
Huanxin Lin,Yao Liu,Zifang Liu,Yong Luo,Conghan Wang,Yaqing Ding,Zeqian Huang,Chunshun Zhao
Metastasis remains the principal driver of breast cancer mortality, a complex process shaped by two key hallmarks: an immunosuppressive tumor microenvironment that facilitates pre-metastatic niche formation and the persistent activation of the pro-metastatic CXCL12–CXCR4 chemokine axis. To simultaneously blockade these drivers, we developed a multifunctional, H 2 O 2 -responsive nanoplatform composed of self-assembled HA-AMD-Cu and the prodrug CBD. This innovative system leverages competitive coordination chemistry to achieve the precise in situ generation of therapeutics specifically within the tumor site. Under the elevated H 2 O 2 levels characteristic of the tumor microenvironment, CBD releases diethyldithiocarbamate (DTC), which effectively competes for Cu 2+ from the HA-AMD-Cu complex. This reaction generates cytotoxic Cu(DTC) 2 while liberating the active multivalent CXCR4 antagonist, HA-AMD. Consequently, Cu(DTC) 2 exerts potent tumor-selective cytotoxicity and induces robust immunogenic cell death (ICD) to reactivate suppressed anti-tumor immunity, while HA-AMD simultaneously inhibits CXCL12-driven metastatic spread. This precise “off-to-on” switch demonstrated significant therapeutic efficacy against both primary tumors and lung metastases in aggressive breast cancer models. Collectively, integrating multivalent CXCR4 blockade with tumor-selective ICD induction provides a promising, targeted strategy for combating metastatic breast cancer.
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DOI
高影响因子
ONCOLOGY REPORTS
·
2020
·Vol. 44
·期 5
·2231-2240
·
IF 3.417
Jinhong Feng,Ting Zheng,Zhaohua Hou,Cui Lv,Anqi Xue,Tingting Han,Beibei Han,Xin Sun,Yunbo Wei
Estrogen receptor (ER)‑negative breast tumors are associated with low survival rates, which is related to their ability to grow and metastasize into distal organs. The aryl hydrocarbon receptor (AhR), a ligand‑activated transcription factor that is involved in several biological processes, is a promising anti‑metastatic target. Luteolin, a non‑toxic naturally occurring plant flavonoid with diverse biological activities, has been demonstrated to be effective against certain types of cancer, and has also been described as a ligand of AhR. In the present study, various cancer cell lines were first investigated following treatment with luteolin, and luteolin exhibited the lowest IC50 in MDA‑MB‑231 cells. Then, the efficiency of luteolin in suppressing the metastasis of ER‑negative breast cancer in vitro was assessed. MDA‑MB‑231 cells were treated with luteolin in vitro. Subsequently, MTT assay and flow cytometry were used to detect cell viability, the cell cycle and apoptosis, and a Transwell assay was used to evaluate cell invasion. In addition, reverse transcription‑semi‑quantitative PCR and western blot were performed to detect the mRNA and protein expression levels of matrix metalloproteinase (MMP)‑2 and MMP‑9. In addition, the number of surface tumor nodules was measured in vivo, in mice bearing B16‑F10 tumors, following treatment with luteolin. Luteolin inhibited the viability and induced the apoptosis of MDA‑MB‑231 cells, which was accompanied by cell cycle arrest. This was associated with a decrease in the expression of the pro‑metastatic markers C‑X‑C chemokine receptor type 4 (CXCR4), MMP‑2 and MMP‑9, which was reversed by AhR inhibition. Furthermore, it was identified that luteolin could inhibit the metastasis in a B16F10 mouse xenograft model, and the levels of MMP‑9, MMP‑2 and CXCR4 were significantly decreased in the lung tissues isolated from tumor‑bearing nude mice following luteolin treatment. In conclusion, luteolin is a potential molecule for inhibiting breast cancer invasion and metastasis, which could have promising clinical applications.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Xinru Chen,Xiaoyan Wang,Jin Li
Raman spectroscopy in the second near-infrared (NIR-II, 1000–1700 nm) window has received ever-increasing attention in intraoperative tumor imaging due to its high specificity and penetration depth. However, the overwhelming majority of existing NIR-II Raman probes are fabricated by SERS with substrate enhancement, which raises serious biosafety concerns. Herein, we present van der Waals (vdW) enhanced Raman scattering (vdW-ERS) effect based on intermolecular charge transfer of dithiolene to develop ultrabright metal-free NIR-II Raman probes. The intermolecular charge transfer within dithiolene through vdW stacking is well illustrated by independent gradient model and ultrafast spectroscopy, which significantly boosts the intrinsic Raman properties with ultrahigh scattering cross-section (1.59 × 10 −19 cm 2 ) as well as the photothermal conversion efficacy (60.4%) through an additional femtosecond-scale non-radiative decay channel. Moreover, the fluorescence-free property of dithiolene greatly inhibits the spectral backgrounds and improves the photostability. In the tumor models of triple-negative breast cancer, vdW-ERS probes enable intraoperative CXCR4-targeted Raman-guided surgical resection and postoperative hyperthermia ablation of the residual microscopic tumors, resulting in approximately 100% survival rate. Importantly, vdW-ERS probes are hepatically excreted (ca. 92% excretion within two months), in stark contrast to accumulation in the liver for typical gold substrate-enhanced counterparts. Free from fluorescence background and photobleaching, intermolecular vdW-ERS effect presents a new mechanism for fabricating charge transfer Raman probes with the potential for clinical translation.
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高影响因子
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