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MACROMOLECULAR RAPID COMMUNICATIONS · 2022 ·Vol. 44 ·期 4 ·2200705 · IF 5.006

Programmable Thermo-Responsive Actuation of Hydrogels via Light-Guided Surface Growth of Active Layers on Shape Memory Substrates

Guang-Lin Fan,Shu-Wei Wang,Ying-Ying Zhang,Zhao-Tie Liu,Zhong-Wen Liu,Lei Wang,Jin-Qiang Jiang,Guo Li

Hydrogel shape memory and actuating functionalities are heavily pursued and have found great potential in various application fields. However, their combination for more flexible and complicated morphing behaviors is still challenging. Herein, it is reported that by controlling the light-initiated polymerization of active hydrogel layers on shape memory hydrogel substrates, advanced morphing behaviors based on programmable hydrogel shapes and actuating trajectories are realized. The formation and photo-reduction-induced dissociation of Fe 3+ -carboxylate coordination endow the hydrogel substrates with the shape memory functionality. The photo-reduced Fe 2+ ions can diffuse from the substrates into the monomer solutions to initiate the polymerization of the thermally responsive active layers, whose actuating temperatures and amplitudes can be facially tuned by controlling their thicknesses and compositions. One potential application, a shape-programmable 3D hook that can lift an object with a specific shape, is also unveiled. The demonstrated strategy is extendable to other hydrogel systems to realize more versatile and complicated actuating behaviors.

CAS / MDL: 2210-25-5 9005-38-3
研究领域: 材料科学 · 生物医学工程
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LANGMUIR · 2020 · IF 3.557

Phototropic Aggregation and Light-Guided Long-Distance Collective Transport of Colloidal Particles

Xiaoran Wu,Xiang Xue,Jinghang Wang,Hewen Liu

Phoretic swarming and collective transport of colloidal particles in response to environmental stimuli have attracted tremendous interest in a variety of fields. In this work, we investigate the light-actuated motion, aggregation, and light-guided long-distance mass transport of silica microspheres in simple spiropyran solutions under the illumination of UV spot sources. The phototactic motion is confirmed by the dependence of swarming on the illumination intensity and spiropyran concentrations, ON–OFF switching tests, pattern-masked UV sources, etc. The aggregates formed via swarming of silica spheres can chase after a moving UV source, however, relying on a critical speed of the UV source. Only when the UV source speed is below the critical value, the aggregates follow the UV spot at a constant relative speed to the light spot. Analysis on the shape of silica microsphere currents indicates that continuous illumination of the UV spot source and resultant chemical gradients are important for the formation of steady microsphere currents. Light-guided aggregation and long-distance mass transport are interesting for targeted delivery and remote-controlled enrichment of environmental hazards.

研究领域: 材料科学 · 物理学 · 化学
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Acta Biomaterialia · 2021 · IF 8.947

Sensitive and precise visually guided drug delivery nanoplatform with dual activation of pH and light

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 · 药理学 · 肿瘤学
✓ 已验证 DOI PubMed 高影响因子
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EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING · 2021 ·Vol. 49 ·期 8 ·2605-2617 · IF 9.236

A pure nanoICG-based homogeneous lipiodol formulation: toward precise surgical navigation of primary liver cancer after long-term transcatheter arterial embolization

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.

CAS / MDL: 3599-32-4
研究领域: 肿瘤学 · 生物医学工程 · 影像医学
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INORGANICA CHIMICA ACTA · 2024 · IF 2.7

Novel biocompatible pH-fluorescence responsive MOF nanocarriers for lung cancer treatment

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.

CAS / MDL: 25316-40-9
研究领域: 材料科学 · 肿瘤学 · 药剂学
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Advanced Healthcare Materials · 2023 · IF 10

Tumor Microenvironment-Responsive Hydrogel for Direct Extracellular ATP Imaging-Guided Surgical Resection with Clear Boundaries

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.

CAS / MDL: 110-26-9 56-65-5
研究领域: 生物医学工程 · 癌症研究 · 材料科学 · 外科肿瘤学
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ADVANCED MATERIALS · 2022 ·Vol. 34 ·期 34 ·2201888 · IF 32.086

Magnetic Microswarm and Fluoroscopy-Guided Platform for Biofilm Eradication in Biliary Stents

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 · 微型机器人技术 · 传染病学 · 医学影像
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Ultrabright NIR-IIb Fluorescence Quantum Dots for Targeted Imaging-Guided Surgery

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.

CAS / MDL: 7664-41-7
研究领域: 生物医学工程 · 纳米技术 · 癌症研究 · 医学成像
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Biomaterials Science · 2021 ·Vol. 10 ·期 2 ·524-535 · IF 6.843

A confined crosslinking strategy towards an intelligent organosilica–micellar hybrid drug delivery system

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.

CAS / MDL: 919-30-2
研究领域: 药学 · 纳米技术 · 生物医学工程 · 癌症治疗
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Journal of Materials Chemistry B · 2025 · IF 5.7

A redox-responsive NIR fluorescent nanoprobe for tumor microenvironment-activated surgical navigation with submillimeter precision

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 · 肿瘤学 · 纳米技术 · 分子成像 · 外科肿瘤学
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Biofabrication · 2023 · IF 9

Laser-guided programmable construction of cell-laden hydrogel microstructures for in vitro drug evaluation

Jianpei Dong,Jianhua Zhou,Hao Tang,Baiqi Chen,Lu Huang

Cell-laden hydrogel microstructures have been used in broad applications in tissue engineering, translational medicine, and cell-based assays for pharmaceutical research. However, the construction of cell-laden hydrogel microstructures in vitro remains challenging. The technologies permitting generation of multicellular structures with different cellular compositions and spatial distributions are needed. Herein, we propose a laser-guided programmable hydrogel-microstructures-construction platform, allowing controllable and heterogeneous assembly of multiple cellular spheroids into spatially organized multicellular structures with good bioactivity. And the cell-laden hydrogel microstructures could be further leveraged for in vitro drug evaluation. We demonstrate that cells within hydrogels exhibit significantly higher half-maximal inhibitory concentration values against doxorubicin (DOX) compared with traditional 2D plate culture. Moreover, we reveal the differences in drug responses between heterogeneous and homogeneous cell-laden hydrogel microstructures, providing valuable insight into in vitro drug evaluation.

研究领域: 组织工程 · 转化医学 · 药物研究 · 生物技术 · 细胞生物学
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Acta Biomaterialia · 2024 · IF 9.4

Zirconium-Containing Nanoscale Coordination Polymers for Positron Emission Tomography and Fluorescence-Guided Cargo Delivery to Triple-Negative Breast Tumors

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.

CAS / MDL: 25952-53-8
研究领域: 生物医学工程 · 纳米技术 · 癌症研究 · 分子成像 · 药物递送系统
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