LANGMUIR
·
2026
·
IF 4.4
Youli Zhang,Lulu Wang,Yanmin Zheng,Lei Zhu,Dongsheng Li,Xinwei Zheng
Balancing the thermodynamic stability and biological clearance of supramolecular assemblies represents a fundamental challenge in the design of functional nanomedicines. To address this, we propose a concentration-responsive “assemble-for-uptake, disassemble-for-clearance” strategy implemented via rational molecular engineering of a minimalist, single-component Gd–DOTA amphiphile. We demonstrate that the alkyl chain length acts as a precise molecular dial to tune the critical micelle concentration (CMC), thereby dictating micellar stability, biological identity, and clearance pathways. Through this tuning, we identified Gd–C12 as the optimized agent, which self-assembles into spherical nanomicelles (38.6 ± 8.3 nm) with desirable T1 contrast (r2/r1 < 2) and kinetic stability surpassing unmodified Gd–DOTA. In vivo studies reveal that Gd–C12 provides potent hepatic enhancement (120% increase) via favorable MPS recognition, independent of organic anion-transporting polypeptide (OATP). Crucially, following hepatic uptake, the agent undergoes spontaneous disassembly upon physiological dilution/excretion, facilitating rapid systemic clearance (>97%) to resolve long-term retention concerns. This work presents Gd–C12 as a high-performance, transporter-independent contrast agent that bridges the gap between nanoparticles and small molecules, holding promise for providing reliable hepatic parenchymal enhancement regardless of OATP expression levels.
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PubMed
高影响因子
CHEMICAL & PHARMACEUTICAL BULLETIN
·
2026
·Vol. 74
·期 3
·232-239
·
IF 1.5
Yuhuan Zhao,Yuhe Yang,Xiaorui Ru,Xiaobo Wang,Chunxi Li,Jiangyan Tang,Yun Zhang,Sanhu Gou,Hui Liu,Jingman Ni
To enhance the efficacy of magnetic resonance imaging (MRI), numerous novel contrast agents have been developed, with peptide modification emerging as a promising strategy. The versatility of peptides renders them particularly useful molecules for the fabrication of new molecule. However, the influence of peptide side chain modification on the imaging performance of contrast agents has not been fully explored in existing studies. Herein, we employed XK (ε-DOTA-Gd) X as a Gd-DOTA-peptide template and the X molecule underwent amino acid block substitution. Six Gd-DOTA-peptide complexes were synthesized and their properties, such as relaxivity, biostability, and biocompatibility, were measured and in vitro MRI assays were carried out. The results demonstrated that the Gd-DOTA-peptides exhibited low hemolysis rates and cytotoxicity. In plasma, the half-lives of the Gd-DOTA-peptide contrast agents exceeded 5 h. Relaxation experiments revealed that the Gd-DOTA-peptide achieved a slightly higher relaxation rate compared with the commercial agent Dotarem. Therefore, the amino acid modularize modification on the gadolinium-based MRI contrast agents were effective and worthy of further investigation.
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高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Chaoquan Lai,Rui Cao,Renda Li,Chunfeng He,Xiao Wang,Hui Shi,Chunrong Qu,Kun Qian,Shaoli Song,Wen-Hua Chen,Zhen Cheng
As an important cancer-associated fibroblast-specific biomarker, fibroblast activation protein (FAP) has become an attractive target for tumor diagnosis and treatment. However, most FAP-based radiotracers showed inadequate uptake and short retention in tumors. In this study, we designed and synthesized a novel FAP ligand (DOTA-GPFAPI-04) through assembling three functional moieties: a quinoline-based FAP inhibitor for specifically targeting FAP, a FAP substrate Gly–Pro as a linker for increasing the FAP protein interaction, and a 2,2′,2″,2‴-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) chelator for radiolabeling with different radionuclides. The FAP targeting ability of DOTA-GPFAPI-04 was investigated by molecular docking studies. DOTA-GPFAPI-04 was then radiolabeled with 68Ga to give [68Ga]Ga-DOTA-GPFAPI-04 for positron emission tomography (PET) imaging of glioblastoma. [68Ga]Ga-DOTA-GPFAPI-04 exhibited a purity of >98% and high stability analyzed by radio-HPLC in saline and mouse serum. Cell uptake studies demonstrated the targeting specificity of the probe. Further in vivo pharmacokinetic studies in normal mice demonstrated the quick clearance of the probe. Moreover, compared with the widely studied [68Ga]Ga-FAPI-04, [68Ga]Ga-DOTA-GPFAPI-04 showed much higher U87MG tumor uptake values (4.467 ± 0.379 for [68Ga]Ga-DOTA-GPFAPI-04 and 1.267 ± 0.208% ID/g for [68Ga]Ga-FAPI-04 at 0.5 h post-injection, respectively). The area under the curve based on time–activity curve (TAC) analysis for tumor radioactivity in small animal models was 422.5 for [68Ga]Ga-DOTA-GPFAPI-04 and 98.14 for [68Ga]Ga-FAPI-04, respectively, demonstrating that the former had longer tumor retention time. The tumor-to-muscle (T/M) ratio for [68Ga]Ga-DOTA-GPFAPI-04 reached 9.15 in a U87MG xenograft animal model. PET imaging and blocking assays showed that [68Ga]Ga-DOTA-GPFAPI-04 had specific tumor uptake. In summary, this study demonstrates the successful synthesis and evaluation of a novel FAPI targeting probe, [68Ga]Ga-DOTA-GPFAPI-04, with a Gly–Pro sequence. It shows favorable in vivo glioblastoma imaging properties and relatively long tumor retention, highlighting DOTA-GPFAPI-04 as a promising molecular scaffold for developing FAP targeting tumor theranostic agents.
研究领域:
医学影像学
·
肿瘤学
·
分子生物学
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PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2026
·
IF 4.9
Jie Li,Yuhui Luo,Chengyu Luo,Zixin Yang,Fei Luo,Huajian Gu,Fei Chen,Zongxi He,Suping Li
Abstract Carbonic anhydrase IX (CA IX) is a key biomarker for tumor hypoxia and a promising target for molecular imaging. In this study, we developed [68Ga]Ga-DOTA-L3, a novel small-molecule CA IX-targeted PET tracer. The radiolabeling was optimized to consistently achieve a radiochemical purity of >98% (10 μg precursor, 90 °C, pH 4.5, 10 min), with excellent stability in saline and FBS up to 240 min. In vivo studies demonstrated rapid blood clearance and predominant renal excretion. Surface plasmon resonance analysis demonstrated high-affinity binding of the DOTA-L3 precursor toward CA IX (Kd = 7.60 ± 0.37 nM) with highest affinity observed for CA IX among the tested isoforms. MicroPET/CT imaging (30−240 min p.i.) showed robust tumor accumulation in OSRC-2 (SUVmean = 1.47 ± 0.21) and HT-29 (SUVmean = 1.03 ± 0.12) xenografts, while minimal uptake was observed in CA IX-low FTC-238 tumors (SUVmean = 0.21 ± 0.05) at 60 min p.i. PET-derived tumor uptake showed a strong linear correlation with CA IX expression levels (R2 = 0.976, P < 0.001) across the three tumor models. High tumor-to-muscle and tumor-to-blood ratios further confirm favorable imaging contrast (T/M = 27.53 ± 1.89 and T/B = 24.61 ± 2.35 at 240 min p.i. for OSRC-2 model). These results support [68Ga]Ga-DOTA-L3 as a promising candidate for non-invasive assessment of CA IX-associated hypoxia and as a scaffold for future theranostic development.
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高影响因子
Biomaterials Science
·
2024
·
IF 5.8
Jia-Hua Zou,Li-Li Chen,Yong-Guo Hu,Dong Zhou,Yong Li,Bin Zhang,Xin-Yue Xu,Bo Liu,Jin-Xuan Fan,Yuan-Di Zhao
Accurate tumor detection is crucial for the early discovery and subsequent treatment of small neoplastic foci. Molecular imaging, which combines non-invasiveness, high specificity, and strong sensitivity, excels in diagnosing early tumors and stands out among tumor diagnosis methods. Here, we introduced a dual-modal imaging probe capable of actively targeting tumor cells, suitable for both near-infrared (NIR) fluorescence and magnetic resonance imaging (MRI). Dendritic mesoporous silica was used as a carrier for the probe, encapsulating Ag2S quantum dots (QDs) for NIR fluorescence imaging. Additionally, the probe conjugated the MRI contrast agent Gd-DOTA and cetuximab, which targeted EGFR on the tumor cell membrane surface, to achieve dual-modal imaging in the tumor area. This strategy provided a methodology for the accurate diagnosis of early-stage tumor lesions and guides precise lesion resection during surgery, offering significant potential for clinical application.
研究领域:
生物医学工程
·
分子成像
·
癌症诊断
·
纳米技术
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PubMed
高影响因子
Advanced Science
·
2026
·
IF 14.1
Ruixue Wang,Jian Zhang,Yun li,Liping Qiao,Zhuorui Dong,Dandan Cui,Peirong Bai,Liping Li,Bing Cao,Ruiping Zhang
New Delhi metallo-β-lactamase (NDM)-producing bacteria have posed a significant threat to human health. To navigate this tricky problem, numerous NDM inhibitors have been explored, showing great antibacterial synergy. But there are still be some problems to be tackled, such as suboptimal efficacy, rapid resistance evolution, and high cytotoxicity. Herein, we engineer two macromolecular resistance-reversal agents (MRRAs) via pharmacophore integration: linear (MRRAL) and nanostructured (MRRAN) topologies, both coordinating metal ion chelator-DOTA motif into tunable polycationic scaffolds. And we validate their efficacy through 4 clinically isolated NDM-producing pathogens. MRRAs present excellent effect boosting meropenem (MEM) to fight against those superbugs with the fractional inhibitory concentration indices much less than 0.5. Notably, the nanostructured MRRAN exhibited superior potency compared to its linear counterpart MRRAL under the same concentration of the active group of “DOTA.” Mechanistic studies revealed that MRRAN could achieve bacterial membrane targeting through charge-mediated accumulation, exerting triple-action synergistic mechanisms: 1) physical membrane disruption through powerful local cationic surface interactions and hydrophobic force, 2) precise Zn 2 + depletion from membrane-associated NDM, and 3) localized DOTA enrichment for enhanced metalloenzyme inhibition. Our findings established a paradigm for rational design of macromolecule metalloenzyme inhibitors through spatial organization of pharmacophores, offering a promising therapeutic strategy against NDM-mediated carbapenem resistance.
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高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 8
·2209-2218
·
IF 5.831
Siqi Wang,Wenzhi Ren,Jianhua Wang,Zhenqi Jiang,Madiha Saeed,Lili Zhang,Aiguo Li,Aiguo Wu
At present, transmembrane glycoprotein CD133 highly expressed pancreatic cancer stem cells (PCSCs), with the features of chemotherapeutic/radiotherapeutic resistance and exclusive tumorigenic potential, are considered as the primary cause of metastasis and recurrence in pancreatic cancer, and therefore are an effective target in the disease treatment. Furthermore, with the launch of precision medicine, multifunctional nanoprobes have been applied as an efficient strategy for the magnetic resonance imaging (MRI)-guided photothermal therapy (PTT) of pancreatic cancer. In this research, with the aim of achieving precise MRI-guided PTT in CD133 highly expressed PCSCs, novel bTiO2-Gd-CD133mAb nanoprobes were designed and successfully prepared by loading Gd-DOTA and CD133 monoclonal antibodies on black TiO2 nanoparticles. It was very interesting to find that the r1 relaxivity value of the nanoprobes was 34.394 mM−1 s−1, about 7.5 times that of commercial Magnevist (4.5624 mM−1 s−1), which indicates that the nanoprobes have good potential as MRI T1 contrast agents with excellent performance. Herein, CD133 highly expressed PANC-1 cells were selected and verified as PCSCs model. In vitro experiments demonstrated that the nanoprobes exhibited active-targeting ability in PANC-1 cells, and consequently could specially enhance T1-weighted MR imaging and 808 nm near-infrared (NIR)-triggered PTT efficiency in the PCSCs model. Our study not only provides a new strategy for the effective treatment of pancreatic cancer and its’ stem cells, but also further broadens the application of black TiO2 in the field of cancer theranostics.
研究领域:
癌症研究
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纳米技术
·
医学成像
·
诊疗一体化
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Mengjie Sun,Chang Yin,Zichao Yan,Zi-Jin Wei,Zhouyu Zhang,Wei Wang,Zhi Yuan
Persistent luminescence (PersL) nanoparticles (PLNPs) with excitation-afterglow emission separation character, have brought luciferous prospect for ultrasensitive optical detection to circumvent the weakness of clinical fluorescence modality, benefiting from the strengths of autofluorescence-free, low phototoxicity and superior photostability. Nevertheless, small dimensions of PLNPs (<200 nm, suitable for in vivo diagnosis) synthesized via current procedures are inevitably accompanied with PersL brightness sacrifice. Whereas the past few years have witnessed advances to promote the performance of nanophosphor, proposing a versatile and sustainable approach to boost the excitation absorption capacity, thus amplifying the PersL is of industrywide urgency. Here, we first report a “lanthanide-chelate sensitization” strategy involving Eu-DOTA as strong photon harvester and Zn 2 SnO 4 : Cr 3+ , Eu 3+ (ZSCE) PLNPs as matched acceptor to steadily augment the intensity of obtained ZDE PLNPs via efficacious Förster-type energy transfer. Photobleaching resistant ZDE PLNPs with different DOTA-Eu substitutions enable maximal 3.9-fold luminous brightness and 1.4-fold decay lifetime over bare PLNPs. Cladded with hyaluronic acid (HA), [email protected] PLNPs performed high signal-to-noise ratio imaging and accurate tumors boundary depicting which facilitates PersL-guided breast tumors excision. Strikingly, the “Ln-chelate sensitization” concept could serve as an extensible approach to optimize existing PLNPs, which lightens up new perspectives for ultra-contrastive malignancy navigation.
研究领域:
材料科学
·
生物医学工程
·
纳米技术
·
光学成像
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-17
·
IF 10.2
Pan Qi,Li Ke,Kang Xueqin,Li Kaixuan,Cheng Zihe,Wang Yafei,Xu Yuye,Li Lei,Li Na,Wu Guilong,Yang Sha,Qi Shuo,Chen Guodong,Tan Xiaofeng,Zhan Yonghua,Tang Li,Zhan Wenhua,Yang Qinglai
Orthotopic advanced hepatic tumor resection without precise location and preoperative downstaging may cause clinical postoperative recurrence and metastasis. Early accurate monitoring and tumor size reduction based on the multifunctional diagnostic-therapeutic integration platform could improve real-time imaging-guided resection efficacy. Here, a Near-Infrared II/Photoacoustic Imaging/Magnetic Resonance Imaging (NIR-II/PAI/MRI) organic nanoplatform IRFEP-FA-DOTA-Gd (IFDG) is developed for integrated diagnosis and treatment of orthotopic hepatic tumor. The IFDG is designed rationally based on the core “S-D-A-D-S” NIR-II probe IRFEP modified with folic acid (FA) for active tumor targeting and Gd-DOTA agent for MR imaging. The IFDG exhibits several advantages, including efficient tumor tissue accumulation, good tumor margin imaging effect, and excellent photothermal conversion effect. Therefore, the IFDG could realize accurate long-term monitoring and photothermal therapy non-invasively of the hepatic tumor to reduce its size. Next, the complete resection of the hepatic tumor in situ lesions could be realized by the intraoperative real-time NIR-II imaging guidance. Notably, the preoperative downstaging strategy is confirmed to lower the postoperative recurrence rate of the liver cancer patients under middle and advanced stage effectively with fewer side effects. Overall, the designed nanoplatform demonstrates great potential as a diagnostic-therapeutic integration platform for precise imaging-guided surgical navigation of orthotopic hepatic tumors with a low recurrence rate after surgery, providing a paradigm for diagnosing and treating the advanced tumors in the future clinical translation application. Graphical Abstract
研究领域:
生物医学工程
·
癌症研究
·
医学影像
·
纳米技术
·
诊疗学
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DOI
PubMed
高影响因子
Cancer Nanotechnology
·
2024
·Vol. 15
·期 1
·1-19
·
IF 4.5
Xu Liu,Wu Ruoyu,Ni Jiajing,Jin Lufei,Xu Kaiwei,Zhu Yuchao,Hong Lu,Chen Chunqu,Wang Linwei,Zhu Lubin,Zhou Weijian,Shen Wenqi,Wang Jianhua
Background The tumor-specific immune responses, essential for removing residual lesions and preventing tumor metastases, can be stimulated by tumor-associated antigens (TAAs) released following photothermal therapy (PTT). However, due to the immunosuppressed microenvironment of pancreatic ductal adenocarcinoma (PDAC), the TAAs released by PTT are difficult to induce an effective immune response. In this work, we prepared the mesoporous silica (mSiO 2 ) coated black titanium dioxide (bTiO 2 ) photothermal nanoparticles (NPs) for enhanced photothermal-immunotherapy toward PDAC, in which resiquimod (R848) was loaded and DOTA-Gd was conjugated. The NPs are specified as bTiO 2 @mSiO 2 @Gd/R848 and abbreviated to NPs/R848. R848 as a kind of Toll-like receptor 7/8 agonist can remodel the tumor microenvironment (TME) in PDAC and induce a strong immune response. Furthermore, DOTA-Gd serves as a magnetic resonance imaging (MRI) contrast agent to improve the T 1 -weighted MRI performance of the NPs. Results In vitro results of this study show that NPs/R848 could thermally ablate tumor cells and efficiently trigger dendritic cell (DC) maturation. The results of in vivo investigations demonstrate that the combined use of photothermal-immunotherapy exhibits a significant inhibitory effect on tumor growth. Besides, it promoted maturation of DCs and enhanced infiltration of CD8 + , CD4 + T cells to improve the TME in PDAC. Conclusions Our study anticipates that by encouraging the maturation of DCs, this strategy will improve the TME and enable the successful photothermal-immunotherapy of PDAC.
研究领域:
癌症研究
·
纳米技术
·
免疫学
·
生物医学工程
·
材料科学
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DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Dinghu Weng,Rong Guo,Changling Dong,Yuan Luo,Dasheng Qiu,Liying Xu,Guobin Xu
The aim of this study was to synthesize a quinoline-based MRI contrast agent, Gd-DOTA-FAPI04, and assess its capacity for targeting fibroblast activation protein (FAP)-positive tumors in vivo. Gd-DOTA-FAPI04 was synthesized by attaching a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complex of gadolinium(III) to FAP inhibitor FAPI04. The longitudinal relaxation time (T1) of the contrast agent was measured using a Siemens Prisma 3.0T MR system, and the CCK-8 assay was performed to evaluate its potential cytotoxicity. Male nude mice bearing tumors grown from FAP-expressing fibrosarcoma cells were divided into experimental (n = 4) and control (n = 4) groups, and T1-weighted image enhancement was measured at different times (0, 10, 30, 60, 90, and 120 min) postinjection of Gd-DOTA-FAPI04. The control group received an additional preinjection of excess FAPI04. FAP expression in tumor tissue was investigated by using immunohistochemistry with an anti-FAP antibody. The longitudinal relaxivities of gadodiamide and Gd-DOTA-FAPI04 were measured to be 3.734 mM–1 s–1 and 5.323 mM–1 s–1, respectively. The CCK-8 assay demonstrated that Gd-DOTA-FAPI04 has minimal toxicity to cultured human fibrosarcoma cells. In vivo MRI showed that peak accumulation of Gd-DOTA-FAPI04 in FAP-expressing tumors occurred 1 h postinjection and could be blocked by preinjection of excess FAPI04. Immunohistochemical analysis of harvested tumor tissue supported the above findings. Gd-DOTA-FAPI04 is a promising contrast agent for in vivo imaging of FAP.
研究领域:
医学成像
·
肿瘤学
·
药物化学
·
分子生物学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）