Acta Biomaterialia
·
2021
·
IF 8.947
Chenyu Liu,Hengjun Zhou,Simiao Yu,Hailiang Chen,Ning Wang,Weihe Yao,An-Hui Lu,Weihong Qiao
Controlled-release drug carriers in cancer therapy are the most ideal way to reduce toxicity and improve drug efficacy . Since light stimulation is precise and operable, most multi-stimulation response carriers utilize phototherapy to enhance release efficiency. However, phototoxicity severely limits the application of phototherapy. Herein, we designed and synthesized a Cou-ONB lipid with sensitive fluorescence feedback and multi-stimulus response. COBL liposomes prepared from Cou-ONB lipids will passively aggregate at the tumor and guide phototherapy by fluorescence. More importantly, it can reflect the drug release effect in vivo through its own sensitive fluorescence changes, further enabling precise phototherapy and reducing phototoxicity. In this paper, the multi-stimulus superimposed response and precise fluorescence-guided performance of COBL liposomes were investigated at the molecular, liposome, cellular, and animal levels. Finally, tumor treatment experiments showed that the d -COBL-UV group had the best tumor suppression effect (5.3-fold). This paper highlights a real-time fluorescence-guided multi-stimulus superposition strategy and provides a design idea to precisely implement exogenous stimuli by displaying the degree of drug release, aiming to achieve less toxic and more efficient cancer therapy through timely and precise multi-stimulation. Statement of significance Multi-stimulus responsive drug carriers have been extensively developed in the last decade. Visual guidance is an important tool to achieve precision medicine and precise control of drug release. However, the available visualization materials are more aimed at directing stimulation at the optimal moment. There is little discussion on when to stop exogenous stimulation and how to minimize the damage of stimulation to the patient. Here, we provide a Cou-ONB lipid that not only responds to multiple stimuli, but also provides sensitive feedback on its own dissociation with a fluorescent signal so that physicians can adjust exogenous stimuli in a timely manner. This paper provides insights to facilitate precision drug delivery systems, providing viable design ideas for precise, efficient, and less toxic cancer therapies.
研究领域:
生物医学工程
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药理学
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肿瘤学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
·
2021
·Vol. 49
·期 8
·2605-2617
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IF 9.236
Zhang Yang,Cheng Hongwei,Chen Hu,Xu Peiyao,Ren En,Jiang Yonghe,Li Dengfeng,Gao Xing,Zheng Yating,He Pan,Lin Huirong,Chen Biaoqi,Lin Gan,Chen Aizheng,Chu Chengchao,Mao Jingsong,Liu Gang
Purpose To surmount the critical issues of indocyanine green (ICG), and thus achieving a precise surgical navigation of primary liver cancer after long-term transcatheter arterial embolization. Methods In this study, a facile and green pure-nanomedicine formulation technology is developed to construct carrier-free indocyanine green nanoparticles (nanoICG), and which subsequently dispersed into lipiodol via a super-stable homogeneous lipiodol formulation technology (SHIFT nanoICG) for transcatheter arterial embolization combined near-infrared fluorescence-guided precise hepatectomy. Results SHIFT nanoICG integrates excellent anti-photobleaching capacity, great optical imaging property, and specific tumoral deposition to recognize tumor regions, featuring entire-process enduring fluorescent-guided precise hepatectomy, especially in resection of the indiscoverable satellite lesions (0.6 mm × 0.4 mm) in rabbit bearing VX2 orthotopic hepatocellular carcinoma models. Conclusion Such a simple and effective strategy provides a promising avenue to address the clinical issue of clinical hepatectomy and has excellent potential for a translational pipeline.
研究领域:
肿瘤学
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生物医学工程
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影像医学
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产品关联
DOI
PubMed
高影响因子
INORGANICA CHIMICA ACTA
·
2024
·
IF 2.7
Julaiti Ainiwaer,Abuduxikuer Abudureyimu,Xiaoliang Jing,Qingchao Sun,Edris Awut,Yanchao Deng,Liwei Zhang
In this study, we synthesized two novel metal–organic frameworks [Cd(C 4 H 4 N 2 )(C 12 H 19 P 3 O 9 )]n (1) and {Ca[ Cd ( H 2 O ) 3 ] 2 (C 24 H 15 N 6 O 6 ) 2 }n (2) distinguished by exceptional fluorescence properties. Focusing on 1, we innovatively combined it with hydroxypropyl cellulose (HPC) to create a pH-responsive, fluorescence-guided nanocarrier system (HPC-1@DOX) for targeted delivery of doxorubicin (DOX) in cancer treatment. We thoroughly evaluated the loading and release efficiency of DOX under varied pH conditions, demonstrating sustained and controlled drug release characteristics in vitro, along with substantial drug-loading capacity. Notably, HPC-1@DOX exhibited pH-responsive behavior, releasing DOX preferentially at pH 6.8, indicative of targeted delivery to tumor and inflammatory sites while minimizing release at higher pH values. Moreover, we explored its biological impact, confirming HPC-1@DOX’s ability to up-regulate miR-493-3p expression in lung carcinoma cells, thereby inhibiting proliferation, reducing invasiveness, and inducing apoptosis. This multifunctional nanocarrier system represents a significant advancement towards targeted and effective cancer therapy.
研究领域:
材料科学
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肿瘤学
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药剂学
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产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Jingyi Yang,Jiahao Qu,Xuanming Teng,Weiping Zhu,Yufang Xu,Yangyang Yang,Xuhong Qian
Most solid tumors are clinically treated using surgical resection, and the presence of residual tumor tissues at the surgical margins often determines tumor survival and recurrence. Herein, a hydrogel (Apt-HEX/Cp-BHQ1 Gel, termed AHB Gel) is developed for fluorescence-guided surgical resection. AHB Gel is constructed by tethering a polyacrylamide hydrogel and ATP-responsive aptamers together. It exhibits strong fluorescence under high ATP concentrations corresponding to the TME (100–500 µ m ) but shows little fluorescence at low ATP concentrations (10–100 n m ) such as those in normal tissues. AHB Gel can rapidly (within 3 min) emit fluorescence after exposure to ATP, and the fluorescence signal only occurs at sites exposed to high ATP, resulting in a clear boundary between the ATP-high and ATP-low regions. In vivo, AHB Gel exhibits specific tumor-targeting capacity with no fluorescence response in normal tissue, providing clear tumor boundaries. In addition, AHB Gel has good storage stability, which is conducive to its future clinical application. In summary, AHB Gel is a novel tumor microenvironment-targeted DNA-hybrid hydrogel for ATP-based fluorescence imaging. It can enable the precise imaging of tumor tissues, showing promising application in fluorescence-guided surgeries in the future.
研究领域:
生物医学工程
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癌症研究
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材料科学
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外科肿瘤学
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2022
·Vol. 34
·期 34
·2201888
·
IF 32.086
Mengmeng Sun,Kai Fung Chan,Zifeng Zhang,Lu Wang,Qinglong Wang,Shihao Yang,Shannon Melissa Chan,Philip Wai Yan Chiu,Joseph Jao Yiu Sung,Li Zhang
Biofilm eradication from medical implants is of fundamental importance, and the treatment of biofilm-associated pathogen infections on inaccessible biliary stents remains challenging. Magnetically driven microrobots with controlled motility, accessibility to the tiny lumen, and swarm enhancement effects can physically disrupt the deleterious biostructures while not developing drug resistance. Magnetic urchin-like capsule robots (MUCRs) loaded with magnetic liquid metal droplets (MLMDs, antibacterial agents) are designed using natural sunflower pollen, and the therapeutic effect of swarming MUCR@MLMDs is explored for eradicating complex mixtures of bacterial biofilm within biliary stents collected from patients. The external magnetic field triggers the emergence of the microswarm and induces MLMDs to transform their shape into spheroids and rods with sharp edges. The inherent natural microspikes of MUCRs and the obtained sharp edges of MLMDs actively rupture the dense biological matrix and multiple species of embedded bacterial cells by exerting mechanical force, finally achieving synergistic biofilm eradication. The microswarm is precisely and rapidly deployed into the biliary stent via endoscopy in 10 min. Notably, fluoroscopy imaging is used to track and navigate the locomotion of microswarm in biliary stents in real-time. The microswarm has great potential for treating bacterial biofilm infections associated with medical implants.
研究领域:
生物医学工程
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微型机器人技术
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传染病学
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医学影像
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
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IF 8.3
Hui Li,Zhong Du,Lijun Zhu,Chi Zhang,Jiabao Xiong,Bingshuai Zhou,Biao Dong,Xueliang Zhang,Nuernisha Alifu
Pioneering approaches for precise tumor removal involve fluorescence-guided surgery, while challenges persist, including the low fluorescence contrast observed at tumor boundaries and the potential for excessive damage to normal tissue at the edges. Lead/cadmium sulfide quantum dots (PbS@CdS QDs), boasting high quantum yields (QYs) and vivid fluorescence, have facilitated advancements in the second near-infrared window (NIR-II, 900–1700 nm). However, during fluorescent surgical navigation operations, hydrophilic coatings of these inorganic nanoparticles (NPs) guarantee biosafety; it also comes at the expense of losing a significant portion of QY and NIR-II fluorescence, causing heightened damage to normal tissues caused by cutting edges. Herein, we present hydrophilic core–shell PbS@CdS@PEG NPs with an exceptionally small diameter (∼8 nm) and a brilliant NIR-IIb (1500–1700 nm) emission at approximately 1600 nm. The mPEG-SH (MW: 2000) addresses the hydrophobicity and enhances the biosafety of PbS@CdS QDs. In vivo fluorescence-guided cervical tumor resection becomes achievable immediately upon injection of an aqueous solution of PbS@CdS@PEG NPs. Notably, this approach results in a significantly reduced thickness (100–500 μm) of damage to normal tissues at the margins of the resected tumors. With a high QY (∼30.2%) and robust resistance to photobleaching, NIR-IIb imaging is sustained throughout the imaging process.
研究领域:
生物医学工程
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纳米技术
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癌症研究
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医学成像
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 10
·期 2
·524-535
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IF 6.843
Xing Qin,Limei Qin,Jianping He,Qinghua Wang,Yongsheng Li,Dechao Niu
An ideal drug delivery system must have a high level of stability to ensure effective circulation and passive aggregation, good retention performance, and dynamic delivery and treatment monitoring. Thus, the development of a smart drug delivery carrier with both precise drug release and real-time detection remains a challenge. Herein, we propose a confined crosslink protocol to prepare an intelligent hybrid delivery system for auto-fluorescent monitoring, protonation-induced retention and precise drug release. The construction of this system involves the hydrolysis and condensation of (3-aminopropyl)triethoxysilane (APTES) silanes inside the Pluronic polymer micelles and thereafter a confined Schiff base crosslinking between glutaraldehyde (GA) and residual silane amino groups. The size of the intelligent docetaxel (DTX)-loaded nanosystem changes from ∼25 nm in blood circulation or normal tissues (pH ∼ 7.4) to ∼250 nm in slightly acidic environments (pH ∼ 6.5–7.0) owing to intra-molecular hydrogen bond-induced aggregation and imine cleavage-induced disintegration in the endosome (pH ∼ 5.0–6.2) along with auto-fluorescent monitoring contributing to the high-efficiency chemotherapy. This work provides a new method to construct smart, acid-responsive and fluorescent-guided drug-delivery carrier systems for efficient and safe tumor chemotherapy.
研究领域:
药学
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纳米技术
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生物医学工程
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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2025
·
IF 5.7
Jian Sun,Jintao Ye,Wenwei Tang,Bin Yu,Yong Gao,Shengli Wang,Haijuan Zhang
Surgical precision in tumor resection critically relies on real-time intraoperative imaging, yet conventional probes face limitations in specificity and spatiotemporal control. Here, we present a tumor microenvironment (TME)-activated near-infrared (NIR) fluorescent nanoprobe (DNS–DYE/PEG–NI) that integrates dual responsiveness to hypoxia and glutathione (GSH) for submillimeter-level surgical navigation. The system comprises a GSH-activatable NIR fluorophore (λex/em = 679/730 nm) quenched by 2,4-dinitrobenzenesulfonyl (DNS) moieties and hypoxia-sensitive amphiphilic PEG–NI micelles. Upon tumor accumulation via the enhanced permeability and retention (EPR) effect, a hypoxic TME triggers micelle disassembly through nitroimidazole (NI) reduction, releasing DNS–DYE. Subsequent GSH cleavage restores fluorescence via intramolecular charge transfer (ICT) recovery, achieving a 12.3-fold tumor-to-normal tissue signal ratio and >90% reduction in off-target activation compared to non-responsive controls. Systematic validation demonstrates: (1) dose-dependent fluorescence recovery (35-fold intensity increase at 10 mM GSH); (2) hypoxia-driven micelle destabilization (800% hydrodynamic diameter expansion); (3) sustained colloidal stability (12.9% size variation over 15 days); and (4) low cytotoxicity (cell viability >90% at 125 μg mL−1). In vivo studies reveal precise tumor delineation within 12 h post-injection, enabling real-time resection of submillimeter lesions. By coupling TME-specific activation with prolonged tumor retention, this dual-responsive nanoprobe advances fluorescence-guided surgery toward precision oncology, reducing positive margin rates from 70% to <5% in preclinical models.
研究领域:
生物医学工程
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肿瘤学
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纳米技术
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分子成像
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外科肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Yan-Ping Li,Zi-Wen Pan,Yan-Jun Jiang,Ya-Yun Peng,Ting Cai,Hao Hong,Xiao-feng Wang
Nanoscale coordination polymer (NCP) is a class of hybrid materials formed by self-assembly of metal ions and organic ligands through coordination. The applications of NCP in biomedicine are quite extensive due to the diversity choice of metal ions and organic ligands. Here we designed Zr-P1 NCP based on Zr 4+ selected as metal ion nodes and tetrakis(4-carboxyphenyl) ethylene as bridging ligands. Zr-P1 NCP was modified with functionalized pyrene derived polyethylene glycol (Py-PAA-PEG-Mal) on the surface and further conjugated with cRGD for active targeting of integrin α v β 3 overexpressed in triple-negative breast cancer. Doxorubicin was loaded on Zr-P1 NCP with encapsulation efficiency up to 22% for the treatment of triple negative breast cancer. 89 Zr-P1 NCP can be used for in vivo tumor imaging due to the fluorescence properties resulting from the enhanced aggregation-induced Emission (AIE) behavior of P1 ligands and its positron emission tomography (PET) capability. Cellular evaluation indicated that the functionalized Zr-P1@PEG-RGD presented a good function for tumor cell targeting imaging and doxorubicin could be targeted to triple negative breast cancer when it was loaded onto Zr-P1@PEG-RGD, which corroborated with the in vivo results. In summary, 89 Zr-P1@PEG-RGD can serve as a biocompatible nanoplatform for fluorescence and PET image-guided cargo delivery. Statement of Significance Nanoscale coordination polymer (NCP) is a class of hybrid materials formed by self-assembly of metal ions and organic ligands through coordination. The diversity of available metals and ligand structures upon NCP synthesis plays an advantage in establishing multimodal imaging platforms. Here we designed 89 Zr-P1@PEG-RGD NCP based on Zr 4+ selected as metal ion nodes and tetrakis(4-carboxyphenyl) ethylene as bridging ligands. 89 Zr-P1@PEG-RGD nanomaterials have positron emission tomography (PET) capability due to the incorporation of zirconium-89, which can be used for in vivo tumor imaging with high sensitivity. The chemotherapeutic drug DOX was loaded on Zr-P1 NCP for the treatment of triple-negative breast cancer, and dual modality imaging can provide visual guidance for drug delivery.
研究领域:
生物医学工程
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纳米技术
·
癌症研究
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分子成像
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2023
·Vol. 16
·期 5
·7280-7292
·
IF 9.9
Sun Yue,Wang Yihui,Han Ruyin,Ren Ziwei,Chen Xin,Dong Wenzhuo,Choi Stephen,Liu Quanhong,Wang Xiaobing
Sonodynamic therapy (SDT) has attracted great interest in the field of cancer therapy because of its non-invasiveness, deep penetration, and spatiotemporal controllability. However, the sonodynamic effect is severely hindered by hypoxia and a high glutathione (GSH) level in tumor microenvironment. In this work, a new type of nanohybrid sonosensitizer is designed, which incorporates several prominent advantages of organic, inorganic, and natural sonosensitizers for imaging-guided SDT and ferroptosis induction. As an endogenous transporter, hemoglobin (Hb) has dual functions of oxygen and iron supplement. Apparently, Hb can transport iron to the tumor site for Fe-dependent ferroptosis, yet this oxygen carrier is able to enhance the sensitivity of tumor cells to oxygen-driven SDT. We innovatively hybridized Hb, sinoporphyrin sodium (DVDMS), and titanium dioxide (TiO 2 ) to prepare an integrated nano-oxygen carrier (designated as HDT) for multifarious cancer theranostics, which not only attained satisfactory sonosensitization of DVDMS/TiO 2 but also achieved oxygen-boosted SDT and potent ferroptosis via Hb. Under ultrasound irradiation, the oxygenation of HDT markedly amplified the generation of reactive oxygen species (ROS) in hypoxic tumors, promoted the valence transition of Hb to accelerate Fenton reaction, and led to ferroptosis. This strategy virtually eradicated tumors in situ and exhibited immunoregulatory potential for augmenting anti-tumor effects in vivo and in vitro through ROS formation, O 2 self-supplement, GSH depletion, and lipid peroxidation. Collectively, HDT demonstrated excellent dual-modal imaging performance, providing a valuable platform for photoacoustic/fluorescence-guided SDT and ferroptosis induction in tumor cells.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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分子生物学
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成像技术
✓ 已验证
产品关联
DOI
高影响因子
MICROCHIMICA ACTA
·
2022
·Vol. 189
·期 10
·1-13
·
IF 6.408
Gao Minjie,Han Zehua,Wang Zhihua,Zou Xueyan,Peng Lichao,Zhao Yanbao,Sun Lei
A novel near-infrared (NIR) light-triggered smart nanoplatform has been developed for cancer targeting and imaging-guided combined photothermal-chemo treatment. Notably, Ag 2 S has a dual function of photothermal therapy and fluorescence imaging, which greatly simplifies the structure of the system. It can emit fluorescence at 820 nm under an excitation wavelength of 560 nm. The phase-change molecule of 1-tetradecanol (TD) is introduced as a temperature-sensitive gatekeeper to provide the nanocarrier with controlled release capability of doxorubicin (DOX). The nanocarrier (HAg 2 S@mSiO 2 -TD/DOX) shows a high drug loading capacity of 26.3% and exhibits an apparent NIR-responsive DOX release property. Under NIR irradiation, the photothermal effect of HAg 2 S nanocores facilitated the release of DOX through the melting of TD. The cytotoxicity test shows that the nanocarriers have good biocompatibility. As the same time, the synergistic combination leads to a better cancer inhibition effect than individual therapy alone in vitro. Cell uptake tests indicate that the carriers have excellent fluorescence imaging ability and high cellular uptake for HepG2 cells. This work provides a new strategy for the fabrication of smart nanocarriers with simple structures for fluorescence-mediated combination cancer therapy. Graphical abstract Fabrication of a smart drug delivery system based on hollow Ag 2 S@mSiO 2 nanoparticles for fluorescence-guided synergistic photothermal chemotherapy
研究领域:
纳米技术
·
癌症治疗
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药物递送系统
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光热疗法
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荧光成像
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子