Co-reporter:Houjuan Zhu, Yuan Fang, Qingqing Miao, Xiaoying Qi, Dan Ding, Peng Chen, and Kanyi Pu
ACS Nano September 26, 2017 Volume 11(Issue 9) pp:8998-8998
Publication Date(Web):August 25, 2017
DOI:10.1021/acsnano.7b03507
Development of optical nanotheranostics for the capability of photodynamic therapy (PDT) provides opportunities for advanced cancer therapy. However, most nanotheranostic systems fail to regulate their generation levels of reactive oxygen species (ROS) according to the disease microenvironment, which can potentially limit their therapeutic selectivity and increase the risk of damage to normal tissues. We herein report the development of hybrid semiconducting polymer nanoparticles (SPNs) with self-regulated near-infrared (NIR) photodynamic properties for optimized cancer therapy. The SPNs comprise a binary component nanostructure: a NIR-absorbing semiconducting polymer acts as the NIR fluorescent PDT agent, while nanoceria serves as the smart intraparticle regular to decrease and increase ROS generation at physiologically neutral and pathologically acidic environments, respectively. As compared with nondoped SPNs, the NIR fluorescence imaging ability of nanoceria-doped SPNs is similar due to the optically inactive nature of nanoceria; however, the self-regulated photodynamic properties of nanoceria-doped SPN not only result in dramatically reduced nonspecific damage to normal tissue under NIR laser irradiation but also lead to significantly enhanced photodynamic efficacy for cancer therapy in a murine mouse model. This study thus provides a simple yet effective hybrid approach to modulate the phototherapeutic performance of organic photosensitizers.Keywords: cancer therapy; nanomedicine; near-infrared light; photodynamic therapy; polymer nanoparticles;
Co-reporter:Duo Mao, Jie Liu, Shenglu Ji, Ting Wang, Yu Hu, Donghui Zheng, Renqiang Yang, Deling Kong, Dan Ding
Biomaterials 2017 Volume 143(Volume 143) pp:
Publication Date(Web):1 October 2017
DOI:10.1016/j.biomaterials.2017.07.038
To date, there have been few studies on using fluorescent cell trackers for non-invasively monitoring the in vivo fate of systemically administered cells. This is because only a relatively small number of cells can reach the disease site post systemic infusion, and thus achieving ideal in vivo cell tracking requires that the fluorescent cell trackers should hold combined merits of ultrahigh near-infrared (NIR) fluorescence, negligible interference on cell behavior and function, excellent retention within cells, as well as accurate long-term cell tracking ability. To address this challenge, we herein developed a highly NIR fluorescent nanoprobe (SPN) based on semiconducting π-conjugated polymers (SPs), by synthesis of a NIR SP-emitter, employment of fluorescence resonance energy transfer (FRET) strategy, and optimization of different FRET donor SPs. Due to the 53.7-fold intra-particle amplification of NIR fluorescence, the SPN could track as few as 2000 endothelial cells (ECs) upon intra-arterial injection into critical limb ischemia (CLI)-bearing mice, showing much higher sensitivity in ECs tracking compared with the most popular commercial cell trackers. What's more, the SPN could provide precise information on the behaviors of systemically injected ECs in CLI treatment including the in vivo fate and regenerative contribution of ECs for at least 21 days.
Co-reporter:Shu Peng;Yu-Chen Pan;Yaling Wang;Zhe Xu;Chao Chen;Yongjian Wang;Dong-Sheng Guo
Advanced Science 2017 Volume 4(Issue 11) pp:
Publication Date(Web):2017/11/01
DOI:10.1002/advs.201700310
AbstractThe introduction of controlled self-assembly into living organisms opens up desired biomedical applications in wide areas including bioimaging/assays, drug delivery, and tissue engineering. Besides the enzyme-activated examples reported before, controlled self-assembly under integrated stimuli, especially in the form of sequential input, is unprecedented and ultimately challenging. This study reports a programmable self-assembling strategy in living cells under sequentially integrated control of both endogenous and exogenous stimuli. Fluorescent polymerized vesicles are constructed by using cholinesterase conversion followed by photopolymerization and thermochromism. Furthermore, as a proof-of-principle application, the cell apoptosis involved in the overexpression of cholinesterase in virtue of the generated fluorescence is monitored, showing potential in screening apoptosis-inducing drugs. The approach exhibits multiple advantages for bioimaging in living cells, including specificity to cholinesterase, red emission, wash free, high signal-to-noise ratio.
Co-reporter:Danni Liu;Shenglu Ji;Heran Li;Liang Hong;Deling Kong;Xin Qi
Faraday Discussions 2017 (Volume 196) pp:377-393
Publication Date(Web):2017/02/20
DOI:10.1039/C6FD00176A
The exploration of advanced fluorescent probes that can detect divalent copper (Cu2+) in aqueous environments and even in live organisms is particularly valuable for understanding the occurrence and development of Cu2+-related diseases. In this work, we report the design and synthesis of an aggregation-induced emission luminogen (AIEgen)-based probe (TPE-Py-EEGTIGYG) by integrating an AIEgen, TPE-Py, with a peptide, EEGTIGYG, which can selectively detect Cu2+ in both aqueous solution and live cells. Peptide EEGTIGYG has dual functionality in the probe design, namely improving water solubility and providing specific cell membrane-binding ability. TPE-Py-EEGTIGYG can self-assemble into nanoaggregates at high concentration in aqueous solution (e.g., 25 μM), which possess large fluorescence output due to the restriction of intramolecular rotation of the phenyl rings on TPE-Py. The fluorescence of the TPE-Py-EEGTIGYG nanoaggregates can be significantly quenched by Cu2+ but not by other metal ions, achieving the selective detection of Cu2+ in aqueous media. Furthermore, TPE-Py-EEGTIGYG can exist as a molecular species and is very weakly fluorescent in dilute aqueous solution (e.g., 5 μM), but can however largely switch on its fluorescence upon specifically anchoring onto the cell membrane. The emissive probes on the cell membrane can be used for the detection of Cu2+ ions that move in and out of cells with a fluorescence “turn-off” mode.
Co-reporter:Chao Chen;Zhegang Song;Xiaoyan Zheng;Zikai He;Bin Liu;Xuhui Huang;Deling Kong;Ben Zhong Tang
Chemical Science (2010-Present) 2017 vol. 8(Issue 3) pp:2191-2198
Publication Date(Web):2017/02/28
DOI:10.1039/C6SC03859J
Photosensitizers are generally treated as key components for photodynamic therapy. In contrast, we herein report an aggregation-induced emission luminogen (AIEgen)-based photosensitizer (TPE-Py-FFGYSA) that can serve as a non-toxic adjuvant to amplify the antitumor efficacy of paclitaxel, a well-known anticancer drug, with a synergistic effect of “0 + 1 > 1”. Besides the adjuvant function, TPE-Py-FFGYSA can selectively light up EphA2 protein clusters overexpressed in cancer cells in a fluorescence turn-on mode, by taking advantage of the specific YSA peptide (YSAYPDSVPMMS)–EphA2 protein interaction. The simple incorporation of FFG as a self-assembly-aided unit between AIEgen (TPE-Py) and YSA significantly enhances the fluorescent signal output of TPE-Py when imaging EphA2 clusters in live cancer cells. Cytotoxicity and western blot studies reveal that the reactive oxygen species (ROS) generated by TPE-Py-FFGYSA upon exposure to light do not kill cancer cells, but instead provide an intracellular oxidative environment to help paclitaxel have much better efficacy. This study thus not only extends the application scope of photosensitizers, but also offers a unique theranostic system with the combination of diagnostic imaging and adjuvant antitumor therapy.
Co-reporter:Jie Liu;Chao Chen;Shenglu Ji;Qian Liu;Dan Zhao;Bin Liu
Chemical Science (2010-Present) 2017 vol. 8(Issue 4) pp:2782-2789
Publication Date(Web):2017/03/28
DOI:10.1039/C6SC04384D
Near infrared (NIR) fluorescence imaging (700–900 nm) is a promising technology in preclinical and clinical tumor diagnosis and therapy. The availability of excellent NIR fluorescent contrast agents is still the main barrier to implementing this technology. Herein, we report the design and synthesis of two series of NIR fluorescent molecules with long wavelength excitation and aggregation-induced emission (AIE) characteristics by fine-tuning their molecular structures and substituents. Further self-assembly between an amphiphilic block co-polymer and the obtained AIE molecules leads to AIE nanoparticles (AIE NPs), which have absorption maxima at 635 nm and emission maxima between 800 and 815 nm with quantum yields of up to 4.8% in aggregated states. In vitro and in vivo toxicity results demonstrate that the synthesized AIE NPs are biocompatible. Finally, the synthesized AIE NPs have been successfully used for image-guided tumor resection with a high tumor-to-normal tissue signal ratio of 7.2.
Co-reporter:Jun Li;Zhipeng Zhu;Shaoqin Rong;Heran Li;Yuenan Guo;Qiang Xue
Biomaterials Science (2013-Present) 2017 vol. 5(Issue 8) pp:1622-1628
Publication Date(Web):2017/07/26
DOI:10.1039/C7BM00270J
Chemotherapy is one of the main categories of clinical cancer treatment. One of the hindrances of a popularly used chemo-drug doxorubicin (DOX) is that some types of cancer cells are or become insensitive/resistant to DOX. In this work, we report a near-infrared (NIR) fluorescent turn-on probe DBT-2EEGYLFFVFER by conjugation of an environment-sensitive fluorophore DBT with human epidermal growth factor receptor 2 (HER2) specific binding peptides. Besides the NIR fluorescence turn-on signature, DBT-2EEGYLFFVFER also has activatable capability of reactive oxygen species (ROS) generation. DBT-2EEGYLFFVFER is weakly fluorescent in aqueous solution and hardly produces ROS under white light irradiation. However, both the NIR fluorescence and ROS production ability can be switched on when DBT-2EEGYLFFVFER binds to HER2 proteins overexpressed in cancer cells. Besides specific visualization of HER2-expressed cancer cells, DBT-2EEGYLFFVFER upon exposure to light is able to effectively increase the intracellular ROS level and offer an intracellular oxidative microenvironment, which does not cause the death of cancer cells, but greatly and synergistically boosts the cytotoxicity of DOX against HER2-expressed cancer cells with a supra-additive effect of “0 + 1 > 1”.
Co-reporter:Xiaoyong Yi, Jun Li, Zhipeng Zhu, Qian Liu, ... Dan Ding
Drug Discovery Today 2017 Volume 22, Issue 9(Volume 22, Issue 9) pp:
Publication Date(Web):1 September 2017
DOI:10.1016/j.drudis.2017.04.004
•AIEgens show unique advantages over conventional fluorescent materials.•AIE nanoparticles (NPs) allow for sensitive cancer diagnosis in vivo.•AIE NPs serve as an advanced theranostic system for cancer diagnosis and treatment.Exploration of a nanoplatform that benefits precise cancer diagnosis and treatment in vivo is particularly valuable. In recent years, aggregation-induced emission luminogens (AIEgens) have emerged as advanced fluorescent materials for the design and preparation of organic nanoparticles (NPs); they also have unique advantages in biomedical applications, especially in cancer diagnosis and theranostics. In this review, we summarize the current status of the development of AIEgen-based NPs for in vivo cancer research, including in vivo tumor diagnosis, drug delivery, and photodynamic therapy. We hope that our review will inspire more exciting research in cross-disciplinary fields, contributing to precise cancer diagnostics and therapeutics.
Co-reporter:Houjuan Zhu, Yuan Fang, Xu Zhen, Na Wei, Yu Gao, Kathy Qian Luo, Chenjie Xu, Hongwei Duan, Dan Ding, Peng Chen and Kanyi Pu
Chemical Science 2016 vol. 7(Issue 8) pp:5118-5125
Publication Date(Web):14 Apr 2016
DOI:10.1039/C6SC01251E
Although organic semiconducting polymer nanoparticles (SPNs) have emerged as an important category of optical imaging agents, their application in molecular imaging is still in its infancy and faces many challenges. We herein report a straightforward one-pot synthetic approach to construct multilayered near-infrared (NIR) fluorescent SPNs with enhanced fluorescence and optimized biodistribution for in vivo molecular imaging. In addition to the SP core, the multilayered SPNs have a middle silica protection layer and an outer poly(ethylene glycol) (PEG) corona, which play crucial roles in enhancing the NIR fluorescence by up to ∼100 fold and reducing nonspecific interactions, respectively. Their proof-of-concept imaging applications are demonstrated in cells, zebrafish and living mice. The multilayered nanoarchitecture not only permits in vivo lymph node tracking with an ultrahigh signal-to-noise ratio (∼85), but also allows for more sensitive in vivo imaging of tumors with a fluorescence intensity ratio of tumor to liver that is ∼8-fold higher compared to that of the counterpart silica SPN. Thus, this study provides a simple yet effective nanoengineering approach to facilitate the application of SPNs in molecular imaging.
Co-reporter:Aitian Han, Huaimin Wang, Ryan T. K. Kwok, Shenglu Ji, Jun Li, Deling Kong, Ben Zhong Tang, Bin Liu, Zhimou Yang, and Dan Ding
Analytical Chemistry 2016 Volume 88(Issue 7) pp:3872
Publication Date(Web):March 7, 2016
DOI:10.1021/acs.analchem.6b00023
Fluorescent light-up probes with aggregation-induced emission (AIE) characteristics have recently attracted great research interest due to their intelligent fluorescence activation mechanism and excellent photobleaching resistance. In this work, we report a new, simple, and generic strategy to design and prepare highly sensitive AIE fluorescent light-up bioprobe through facile incorporation of a self-assembling peptide sequence GFFY between the recognition element and the AIE luminogen (AIEgen). After the bioprobes respond to the targets, the peptide GFFY is capable of inducing the ordered self-assembly of AIEgens, yielding close and tight intermolecular steric interactions to restrict the intramolecular motions of AIEgens for excellent signal output. Using two proof-of-concepts, we have demonstrated that self-assembling peptide-incorporating AIE light-up probes show much higher sensitivity in sensing the corresponding targets in both solutions and cancer cells as compared to those without GFFY induced self-assembly. Taking the probe TPE-GFFYK(DVEDEE-Ac), for example, a detection limit as low as 0.54 pM can be achieved for TPE-GFFYK(DVEDEE-Ac) in caspase-3 detection, which is much lower than that of TPE-K(DVED-Ac) (3.50 pM). This study may inspire new insights into the design of advanced fluorescent molecular probes.
Co-reporter:Guorui Jin;Duo Mao;Pingqiang Cai;Rongrong Liu;Nikodem Tomczak;Jie Liu;Xiaodong Chen;Deling Kong;Bin Liu;Kai Li
Advanced Functional Materials 2015 Volume 25( Issue 27) pp:4263-4273
Publication Date(Web):
DOI:10.1002/adfm.201501081
Stem cell–based therapies hold great promise in providing desirable solutions for diseases that cannot be effectively cured by conventional therapies. To maximize the therapeutic potentials, advanced cell tracking probes are essential to understand the fate of transplanted stem cells without impairing their properties. Herein, conjugated polymer (CP) nanodots are introduced as noninvasive fluorescent trackers with high brightness and low cytotoxicity for tracking of mesenchymal stem cells (MSCs) to reveal their in vivo behaviors. As compared to the most widely used commercial quantum dot tracker, CP nanodots show significantly better long-term tracking ability without compromising the features of MSCs in terms of proliferation, migration, differentiation, and secretome. Fluorescence imaging of tissue sections from full-thickness skin wound–bearing mice transplanted with CP nanodot-labeled MSCs suggests that paracrine signaling of the MSCs residing in the regenerated dermis is the predominant contribution to promote skin regeneration, accompanied with a small fraction of endothelial differentiation. The promising results indicate that CP nanodots could be used as next generation of fluorescent trackers to reveal the currently ambiguous mechanisms in stem cell therapies through a facile and effective approach.
Co-reporter:Guoqin Chen, Yongquan Hua, Caiwen Ou, Xiaoli Zhang, Duo Mao, Zhimou Yang, Dan Ding and Minsheng Chen
Chemical Communications 2015 vol. 51(Issue 53) pp:10758-10761
Publication Date(Web):28 May 2015
DOI:10.1039/C5CC01349F
We report the design and synthesis of a light-up probe of DBT-2(EEGK-maleimide), which can serve as a unique probe for selectively detecting protein thiols in various environments, including aqueous solutions, bacteria and live cells.
Co-reporter:Cuihong Yang, Liping Chu, Yumin Zhang, Yang Shi, Jinjian Liu, Qiang Liu, Saijun Fan, Zhimou Yang, Dan Ding, Deling Kong, and Jianfeng Liu
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 4) pp:2735
Publication Date(Web):January 2, 2015
DOI:10.1021/am507800e
Self-assembling peptide nanofibers (including naturally l-amino acid–based and unnaturally d-amino acid–based ones) have been widely utilized in biomedical research. However, there has been no systematic study on their in vivo stability, distribution, and toxicity. Herein we systematically study the in vivo dynamic biostability, biodistribution, and toxicity of supramolecular nanofibers formed by Nap-GFFYGRGD (l-amino acid-based, l-fibers) and Nap-GDFDFDYGRGD (d-amino acid–based, d-fibers), respectively. The d-fibers have better in vitro and in vivo biostabilities than l-fibers. It is found that d-fibers keep a good integrity in plasma during 24 h, while half of l-fibers are digested upon incubation in plasma for 6 h. The biodistributions of l- and d-fibers are also studied using the iodine-125 radiolabeling technique. The results reveal that l-fibers mainly accumulate in stomach, whereas d-fibers preferentially distribute in liver. Successive administrations of both l- and d-fibers with the dose of 30 mg/kg/dose cause no significant inflammation, liver and kidney function damages, immune reaction, and dysfunction of hematopoietic system. This study will provide fundamental guidelines for utilization of self-assembling peptide-based supramolecular nanomaterials in biomedical applications, such as drug delivery, bioimaging, and regenerative medicine.Keywords: biodistribution; biostability; in vivo toxicity; l/d-peptides; self-assembling nanofibers
Co-reporter:Ran Tian, Huaimin Wang, Ruifang Niu, Dan Ding
Journal of Colloid and Interface Science 2015 Volume 453() pp:15-20
Publication Date(Web):1 September 2015
DOI:10.1016/j.jcis.2015.04.028
HypothesisSupramolecular nanostructures via small molecule self-assembly hold great promise for controlled delivery of hydrophobic anticancer drugs. Particularly, taxol has recently been discovered to possess excellent self-assembly property, which may provide new opportunities to develop a new class of functional supramolecular nanomaterials for drug delivery application.ExperimentsA cell penetrating peptide (CPP)–taxol conjugate (Taxol–CPP) was designed and synthesized. The self-assembling property of Taxol–CPP was investigated and the resultant nanomaterials were well characterized. Subsequently, the cytotoxicity of the Taxol–CPP after self-assembly against HepG2 cancer cells was evaluated.FindingsIt is found that the Taxol–CPP possesses a high drug loading of 26.4% in each molecule, which is able to self-assemble into supramolecular nanospheres. By taking advantages of the self-assembly ability of taxol, Taxol–CPP supramolecular nanospheres with a mean size of around 130 nm can be obtained, composed of only the functional peptide (CPP) and the drug (taxol). Furthermore, we have demonstrated that the Taxol–CPP nanospheres do not compromise the taxol’s potency, which can also be utilized as the carriers for co-delivery of another anticancer drug (doxorubicin).
Co-reporter:Jianfeng Liu, Jinjian Liu, Liping Chu, Yumin Zhang, Hongyan Xu, Deling Kong, Zhimou Yang, Cuihong Yang, and Dan Ding
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 8) pp:5558
Publication Date(Web):March 24, 2014
DOI:10.1021/am406007g
d-peptides, which consist of d-amino acids and can resist the hydrolysis catalyzed by endogenous peptidases, are one of the promising candidates for construction of peptide materials with enhanced biostability in vivo. In this paper, we report on a self-assembling supramolecular nanostructure of d-amino acid-based peptide Nap-GDFDFDYGRGD (d-fiber, DF meant d-phenylalanine, DY meant d-tyrosine), which were used as carriers for 10-hydroxycamptothecin (HCPT). Transmission electron microscopy observations demonstrated the filamentous morphology of the HCPT-loaded peptides (d-fiber-HCPT). The better selectivity and antitumor activity of d-fiber-HCPT than l-fiber-HCPT were found in the in vitro and in vivo antitumor studies. These results highlight that this model d-fiber system holds great promise as vehicles of hydrophobic drugs for cancer therapy.Keywords: 10-hydroxycamptothecin; d-peptide; hydrophobic drug delivery; nanofiber; self-assembly;
Co-reporter:Xiaoli Zhang;Hao Zhou;Ying Xie;Chunhua Ren;Jiafu Long;Zhimou Yang
Advanced Healthcare Materials 2014 Volume 3( Issue 11) pp:1804-1811
Publication Date(Web):
DOI:10.1002/adhm.201300660
A hetero-hexameric protein system is developed in this study, which not only functions as cross-linkers for hydrogel formation but also offers docking sites for controlled delivery of bioactive molecules. First, a hexameric protein with two, four, and six tax-interacting protein-1 (TIP-1), respectively (named as 2T, 4T, and 6T), is designed and obtained. As the hexapeptide ligand (WRESAI) can specifically bind to TIP-1 with high affinity, the hexameric proteins of 2T, 4T, and 6T can be used to crosslink the self-assembling nanofibers of Nap-GFFYGGGWRESAI, leading to formation of injectable biohybrid hydrogels with tunable mechanical properties. Furthermore, a hetero-hexameric protein containing four TIP-1 and two C-terminal moiety of the pneumococcal cell-wall amidase LytA (C-LytA) proteins is designed and engineered (named as 4T2C). The 4T2C proteins can not only serve as cross-linkers for hydrogel formation but also provide docking sites for loading and controlled release of model drug Rhoda-GGK′. This study opens up new opportunities for further development of multifunctional hetero- recombinant protein-based hydrogels for biological applications.
Co-reporter:Weiwei Wang, Guoping Li, Weiguang Zhang, Jie Gao, Jimin Zhang, Chen Li, Dan Ding and Deling Kong
RSC Advances 2014 vol. 4(Issue 57) pp:30168-30171
Publication Date(Web):01 Jul 2014
DOI:10.1039/C4RA03760J
We report here a biocompatible strategy of EFK8-based molecular hydrogel formation via disulfide bond reduction in cell culture media under neutral conditions, which presents a promising approach in three-dimensional (3D) cell culture.
Co-reporter:Huaimin Wang, Jie Liu, Aitian Han, Nannan Xiao, Zhaosheng Xue, Gang Wang, Jiafu Long, Deling Kong, Bin Liu, Zhimou Yang, and Dan Ding
ACS Nano 2014 Volume 8(Issue 2) pp:1475
Publication Date(Web):January 13, 2014
DOI:10.1021/nn4054914
Understanding specific protein–peptide interactions could offer a deep insight into the development of therapeutics for many human diseases. In this work, we designed and synthesized a far-red/near-infrared (FR/NIR) fluorescence light-up probe (DBT-2EEGWRESAI) by simply integrating two tax-interacting protein-1 (TIP-1)-specific peptide ligands (EEGWRESAI) with one 4,7-di(thiophen-2-yl)-2,1,3-benzothiadiazole (DBT) unit. We first demonstrated that DBT is an environment-sensitive fluorophore with FR/NIR fluorescence due to its strong charge transfer character in the excited state. Thanks to the environmental sensitivity of DBT, the probe DBT-2EEGWRESAI is very weakly fluorescent in aqueous solution but lights up its fluorescence when the probe specifically binds to TIP-1 protein or polyprotein (ULD-TIP-1 tetramer). It is found that the DBT-2EEGWRESAI/TIP-1 protein and the DBT-2EEGWRESAI/ULD-TIP-1 tetramer could self-assemble into spherical nanocomplexes and a nanofiber network, respectively, which lead to probe fluorescence turn-on through providing DBT with a hydrophobic microenvironment. By virtue of the self-assembly-induced FR/NIR fluorescence turn-on, DBT-2EEGWRESAI can detect and visualize specific protein/polyprotein–peptide interactions in both solution and live bacteria in a high contrast and selective manner.Keywords: bacteria; environment-sensitive fluorophore; far-red/near-infrared fluorescence; protein−peptide interactions; self-assembly
Co-reporter:Jie Liu, Chao Chen, Shenglu Ji, Qian Liu, Dan Ding, Dan Zhao and Bin Liu
Chemical Science (2010-Present) 2017 - vol. 8(Issue 4) pp:NaN2789-2789
Publication Date(Web):2017/01/20
DOI:10.1039/C6SC04384D
Near infrared (NIR) fluorescence imaging (700–900 nm) is a promising technology in preclinical and clinical tumor diagnosis and therapy. The availability of excellent NIR fluorescent contrast agents is still the main barrier to implementing this technology. Herein, we report the design and synthesis of two series of NIR fluorescent molecules with long wavelength excitation and aggregation-induced emission (AIE) characteristics by fine-tuning their molecular structures and substituents. Further self-assembly between an amphiphilic block co-polymer and the obtained AIE molecules leads to AIE nanoparticles (AIE NPs), which have absorption maxima at 635 nm and emission maxima between 800 and 815 nm with quantum yields of up to 4.8% in aggregated states. In vitro and in vivo toxicity results demonstrate that the synthesized AIE NPs are biocompatible. Finally, the synthesized AIE NPs have been successfully used for image-guided tumor resection with a high tumor-to-normal tissue signal ratio of 7.2.
Co-reporter:Houjuan Zhu, Yuan Fang, Xu Zhen, Na Wei, Yu Gao, Kathy Qian Luo, Chenjie Xu, Hongwei Duan, Dan Ding, Peng Chen and Kanyi Pu
Chemical Science (2010-Present) 2016 - vol. 7(Issue 8) pp:NaN5125-5125
Publication Date(Web):2016/04/14
DOI:10.1039/C6SC01251E
Although organic semiconducting polymer nanoparticles (SPNs) have emerged as an important category of optical imaging agents, their application in molecular imaging is still in its infancy and faces many challenges. We herein report a straightforward one-pot synthetic approach to construct multilayered near-infrared (NIR) fluorescent SPNs with enhanced fluorescence and optimized biodistribution for in vivo molecular imaging. In addition to the SP core, the multilayered SPNs have a middle silica protection layer and an outer poly(ethylene glycol) (PEG) corona, which play crucial roles in enhancing the NIR fluorescence by up to ∼100 fold and reducing nonspecific interactions, respectively. Their proof-of-concept imaging applications are demonstrated in cells, zebrafish and living mice. The multilayered nanoarchitecture not only permits in vivo lymph node tracking with an ultrahigh signal-to-noise ratio (∼85), but also allows for more sensitive in vivo imaging of tumors with a fluorescence intensity ratio of tumor to liver that is ∼8-fold higher compared to that of the counterpart silica SPN. Thus, this study provides a simple yet effective nanoengineering approach to facilitate the application of SPNs in molecular imaging.
Co-reporter:Guoqin Chen, Yongquan Hua, Caiwen Ou, Xiaoli Zhang, Duo Mao, Zhimou Yang, Dan Ding and Minsheng Chen
Chemical Communications 2015 - vol. 51(Issue 53) pp:NaN10761-10761
Publication Date(Web):2015/05/28
DOI:10.1039/C5CC01349F
We report the design and synthesis of a light-up probe of DBT-2(EEGK-maleimide), which can serve as a unique probe for selectively detecting protein thiols in various environments, including aqueous solutions, bacteria and live cells.
Co-reporter:Chao Chen, Zhegang Song, Xiaoyan Zheng, Zikai He, Bin Liu, Xuhui Huang, Deling Kong, Dan Ding and Ben Zhong Tang
Chemical Science (2010-Present) 2017 - vol. 8(Issue 3) pp:NaN2198-2198
Publication Date(Web):2016/12/02
DOI:10.1039/C6SC03859J
Photosensitizers are generally treated as key components for photodynamic therapy. In contrast, we herein report an aggregation-induced emission luminogen (AIEgen)-based photosensitizer (TPE-Py-FFGYSA) that can serve as a non-toxic adjuvant to amplify the antitumor efficacy of paclitaxel, a well-known anticancer drug, with a synergistic effect of “0 + 1 > 1”. Besides the adjuvant function, TPE-Py-FFGYSA can selectively light up EphA2 protein clusters overexpressed in cancer cells in a fluorescence turn-on mode, by taking advantage of the specific YSA peptide (YSAYPDSVPMMS)–EphA2 protein interaction. The simple incorporation of FFG as a self-assembly-aided unit between AIEgen (TPE-Py) and YSA significantly enhances the fluorescent signal output of TPE-Py when imaging EphA2 clusters in live cancer cells. Cytotoxicity and western blot studies reveal that the reactive oxygen species (ROS) generated by TPE-Py-FFGYSA upon exposure to light do not kill cancer cells, but instead provide an intracellular oxidative environment to help paclitaxel have much better efficacy. This study thus not only extends the application scope of photosensitizers, but also offers a unique theranostic system with the combination of diagnostic imaging and adjuvant antitumor therapy.
Co-reporter:Jun Li, Zhipeng Zhu, Shaoqin Rong, Heran Li, Yuenan Guo, Qiang Xue and Dan Ding
Biomaterials Science (2013-Present) 2017 - vol. 5(Issue 8) pp:NaN1628-1628
Publication Date(Web):2017/05/19
DOI:10.1039/C7BM00270J
Chemotherapy is one of the main categories of clinical cancer treatment. One of the hindrances of a popularly used chemo-drug doxorubicin (DOX) is that some types of cancer cells are or become insensitive/resistant to DOX. In this work, we report a near-infrared (NIR) fluorescent turn-on probe DBT-2EEGYLFFVFER by conjugation of an environment-sensitive fluorophore DBT with human epidermal growth factor receptor 2 (HER2) specific binding peptides. Besides the NIR fluorescence turn-on signature, DBT-2EEGYLFFVFER also has activatable capability of reactive oxygen species (ROS) generation. DBT-2EEGYLFFVFER is weakly fluorescent in aqueous solution and hardly produces ROS under white light irradiation. However, both the NIR fluorescence and ROS production ability can be switched on when DBT-2EEGYLFFVFER binds to HER2 proteins overexpressed in cancer cells. Besides specific visualization of HER2-expressed cancer cells, DBT-2EEGYLFFVFER upon exposure to light is able to effectively increase the intracellular ROS level and offer an intracellular oxidative microenvironment, which does not cause the death of cancer cells, but greatly and synergistically boosts the cytotoxicity of DOX against HER2-expressed cancer cells with a supra-additive effect of “0 + 1 > 1”.
![POLY[IMINO[1-(2-CARBOXYETHYL)-2-OXO-1,2-ETHANEDIYL]]](http://img.cochemist.com/ccimg/25800/25736-32-7.png)
![POLY[IMINO[1-(2-CARBOXYETHYL)-2-OXO-1,2-ETHANEDIYL]]](http://img.cochemist.com/ccimg/25800/25736-32-7_b.png)
![Poly[oxy(1-oxo-1,6-hexanediyl)]](http://img.cochemist.com/ccimg/25300/25248-42-4.png)
![Poly[oxy(1-oxo-1,6-hexanediyl)]](http://img.cochemist.com/ccimg/25300/25248-42-4_b.png)
