- Email: [email protected]
Cascade-released nanoassembly for cancer drug delivery
ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575
with disulfiram, which effectively induce apoptosis in tumor cells. Thus, the elevated tumor copper concentration may be exploited for tumor-targeted cancer chemotherapy. Herein, we report a series of water-soluble poly(ethylene glycol)-block– poly(dithiocarbamate) (PEG–PDTC) copolymers (Figure 1, a). The polymer itself had very low cytotoxicity. Addition of copper(II) ions to the PEG–PDTC solutions induced the formation of nanoparticles (Figure 1, b). Compared with the noncytotoxic PEG–PDTC, the PEG–PDTC/Cu2 + nanoparticles exhibited significantly enhanced cytotoxicity against tumor cells (Figure 1, c). The structure–cytotoxicity correlation and the in vivo anticancer activity of the polymers without or with copper ions were studied.
471
bioavailability. Polymorphic transformation would most probably happen during the good-solvent involved recrystallization in tablet preparation. http://dx.doi.org/10.1016/j.nano.2015.12.074
Improving the antitumor efficacy of doxorubicin-loaded PEG–PCL copolymer micelles by down-regulating hedgehog pathway Quan Zhou, Xiangrui Liu⁎, Jianbin Tang, Youqing Shen, Center for Bionanoengineering and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China ⁎Corresponding author. E-mail address: [email protected] (X. Liu)
Figure 1. (a) Copper-induced formation of PEG–PDTC/Cu2 + nanoparticles. (b) The hydrodynamic size of PEG2k-PDTC1.4 k nanoparticles. (c) Effect of copper(II) on the cytotoxicity of PEG–PDTC against BCap37 human breast tumor cells for 48 h.
Pancreatic ductal adenocarcinoma cancer (PDAC) is one of the most lethal human cancers because it is resistant to many chemotherapeutic drugs. In PDAC, tumor stroma makes up the bulk of the tumor tissue. Tumor–stroma interaction not only induces tumor invasion and metastasis, but also reduces the sensitivity and restricts the penetration of nano-sized antitumor agents (nano-drugs), leading to the limited antitumor activity. Our research focuses on modulating tumor–stroma interaction for improving antitumor efficacy of nano-drugs. The hedgehog pathway (HH), abnormal activated in most PDAC, is one of the key signaling between the tumor and tumor stroma cells, and plays an important role in the tumor drug resistance (Olive et al 2009). Here we used GDC-0449, a small molecule that targets the hedgehog pathway to reverse the drug resistance caused by the tumor stroma cells. The in vitro tumor– stroma co-culture model and in vivo pancreatic tumor model provide a more reliable evaluation platform and facilitate mechanism studies. Improved antitumor efficacy was observed in both pancreatic tumor models in vitro and in vivo.
http://dx.doi.org/10.1016/j.nano.2015.12.073
This work was supported by the National Key Basic Research Program of China (2014CB931900) and National Natural Science Foundation of China (51390481).
http://dx.doi.org/10.1016/j.nano.2015.12.075 An investigation on the dissolution, bioavailability and polymorphic transformation of nimodipine during size reduction from microscale to nanoscale and tablet preparation Yue Wang, Yi Li, Junbo Gong⁎, Zhenping Wei⁎, Department of Chemical Engineering and Technology, Tianjin University, Tianjin, China ⁎Corresponding authors. E-mail address: [email protected] (Z. Wei) The carrier-free solubilization technologies have been extensively used to improve the oral bioavailability of poorly soluble drugs in the pharmaceutical industry. In addition to its water insolubility, nimodipine (Nim) is a polymorphic compound, while polymorphs are known to give rise to significant differences in dissolution and bioavailability of drug compound. This paper aimed at investigating the effect of particle size reduction from microscale to nanoscale on the in vitro dissolution and in vivo bioavailability of Nim as well as the polymorphic transformation during the preparation of Nim tablets. Anti-solvent precipitation was carried out to prepare the nimodipine microsuspension (Nim-Ms) and subsequent high-pressure homogenization was applied to obtain nimodipine nanosuspension (Nim-Ns). The suspensions were then freeze-dried and compressed into nimodipine microcrystal-based tablets (Nim-MBT) and nanocrystal-based tablets (Nim-NBT), respectively. The crystal forms of Nim in Nim-Ms, Nim-Ns, Nim-MBT and Nim-NBT were analyzed by the XRPD and DSC to investigate the polymorphic transformation. The in vitro dissolution of Nim-MBT and Nim-NBT in five different media and their oral absorption abilities in rabbits were investigated. The average particle sizes of Nim-Ms and Nim-Ns were 8.26 ± 0.05 μm or 713 ± 160.45 nm, respectively. In the preparation of Nim tablets, microprecipitation was the only process where polymorphic transformation happened. The drug releases from Nim-NBT were faster than those from Nim-MBT in all the media used. The bioavailability in term of AUC0 -24h of Nim-NBT in rabbits was 1.41 times that of Nim-MBT after oral administration. These results demonstrate that size reduction for nimodipine could accelerate drug dissolution and improve oral
Cascade-released nanoassembly for cancer drug delivery Sun Xuanronga,b, Shao Shiquna, Shen youqinga,⁎, aCenter for Bionanoengineering and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, PR China., bCollaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, PR China ⁎Corresponding author. E-mail address: [email protected] (S. youqing)
Current nanomedicines crafted to deliver anticancer agents to tumor tissues have not showed therapeutic efficacy as expected since they cannot efficiently accomplish the whole cancer drug delivery process, i.e., circulation in blood, accumulation and penetration into tumor, internalization into tumor cells and intracellular drug release, or the CAPIR cascade in short. Herein, we present a 40 nm liposomal dendrimer nanoassembly, G4.5/DOX/LC-PEG, which consisted of 27 dendrimers aggregating together coated with a pegylated fusogenic lipid layer. The pegylated nanoassembly's lipid layer could interact with the cell membrane, releasing the 5 nm dendrimers into the cytosol for intracellular drug release or into the tumor interstitial space, which could further penetrate deep into tumor tissue, enabling the carried DOX to reach cells remote from blood capillaries. The DOX-loaded nanoassembly circumvented the drug resistance and showed significantly enhanced in vivo antitumor efficacy with minimized side effects. This nanoassembly may be a promising concept integrating the needed properties for nanomedicine with high chemotherapeutic efficacy (Scheme 1).
This work was supported by the National Key Basic Research Program of China (2014CB931900) and National Natural Science Foundation of China (51390481).
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ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575
Antitumor activity of PEG–PCL/dithiocarbamate-copper nanoparticles Chunwan You, Shiqun Shao, Jianbin Tang, Xiangrui Liu, Youqing Shen⁎, Center for Bionanoengineering and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, China ⁎Corresponding author. E-mail address: [email protected] (Y. Shen)
Scheme 1. The nanoassembly G4.5LC-PEG/DOX structure: the dendrimers were self-assembled with DOPE and DSPE-PEG lipids as well as cholesterol to form the nanoassembly with a dendrimer core and lipidic shell. This nanoassembly G4.5LC-PEG/DOX showed deep penetration ability and exhibited strong antitumor activity than corresponding agents PEG–PCL/DOX in MCF7-ADR tumor model.
http://dx.doi.org/10.1016/j.nano.2015.12.076
A dual fluorescent prodrug for in vivo tumor imaging and therapy Minghzou Yea, Xiaohang Wangb, Jianbin Tanga,⁎, Zhiqian Guob,⁎, He Tianb, Weihong Zhub,⁎, Youqing Shena, aKey Laboratory of Biomass Chemical Engineering of Ministry of Education and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, China., bInstitute of Fine Chemicals, East China University of Science and Technology, Shanghai, P.R. China ⁎Corresponding authors. E-mail addresses: [email protected] (M. Ye), [email protected] (J. Tang) Meeting the avid demands for improved chemotherapies, GSH triggered theranostic prodrugs have been prosperously developed in the past decade. Owing to the significant GSH concentration differences between cytosol and extracellular fluids, the rational of the designed structures is to keep stable in circulating system but achieve rapid drug release in cells, especially tumor cells. It has been demonstrated by switchable fluorescent prodrugs. However, most of these prodrugs were plagued by their mono-fluorescent channel and short wavelengths, which were insufficient for describing the overall pharmacokinetics, and also severely interfered by tissue autofluorescence. To solve the problem, we linked an NIR dye and anticancer drug CPT using disulfide bond to develop a novel theranostic prodrug with dualfluorescent channels. The prodrug with intact structure emitted fluorescent of 825 nm, but once cleaved by GSH, the fluorescent emission at 650 nm was switched and simultaneous released a CPT drug, which exhibited an enhanced cytotoxicity. The release process and cytotoxicity of the prodrug nanoparticles were carefully examined in vitro, and it was employed to in situ trace the in vivo activation process on xenograft nude mice model. The results demonstrated the structure to be a promising prodrug for both diagnose and therapy.
Figure 1. In vivo imaging (A) and antitumor activities (B) of the theranostic prodrug on xenograft nude mice.
This work was supported by the National Key Basic Research Program of China (2014CB931900) and National Natural Science Foundation of China (51390481).
http://dx.doi.org/10.1016/j.nano.2015.12.077
Many copper complexes have been shown to be effective inhibitors of tumor angiogenesis. Pyrrolidine dithiocarbamate (PDTC) can complex with copper ions, forming an effective inhibitor of NF-κB activation inhibiting VEGF expression, tumor angiogenesis and growth. We synthesized a series of dithiocarbamate compounds (DTCs) similar to PDTC, and discovered new dithiocarbamates which had much higher efficacy in suppression of tumor growth and metastasis. We found that some DTCs could sequestrate the plasma copper owing to their strong copper binding ability. Interestingly, one of the DTC-copper complexes exhibited 40000 times higher cytotoxicity than DTCs themselves with an IC50 as low as 0.15 nM to Bcap37 cancer cells. Hence, DTC-copper complexes may be new potent antitumor drugs. As the complexes are generally water-insoluble, polymer micelles of polyethylene glycol-polycaprolactone (PEG–PCL) were furthermore used to deliver the complexes for intravenous administration. The DTC-copper complexes could be loaded into PEG5K–PCL4.5K micelles with a size of about 76.8 nm. The PEG–PCL/DTC-copper complex micelles showed a slightly reduced cytotoxicity estimated by MTT assay to the breast cell lines, Bcap-37 and MCF7/ADR. Anticancer effect in vivo and antitumor mechanism of the PEG–PCL/DTC-copper complex NPs will be further studied. This work was supported by the National Key Basic Research Program of China (2014CB931900) and National Natural Science Foundation of China (51390481).
http://dx.doi.org/10.1016/j.nano.2015.12.078
A NIR-remote controlled recyclable up-converting nanoparticle: An improved tool for live cell dye-labeling Bin Zheng, Xiaoqun Gong, Linsu, Sheng Wang, Hanjie Wang⁎, Jin Chang, School of Life Sciences, Tianjin University, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, P.R. China ⁎Corresponding author. E-mail addresses: [email protected] (H. Wang), [email protected] (J. Chang) Due to the selective permeability and complicated cellular environment of live cells, it can easily lead to the low cell uptake efficiency and easy fluorescence decay of organic dyes during the dye-labeling in live cells, which will eventually result in the poor fluorescent imaging. In this work, a protocol of UCN@mSiO2-(FA and Azo) core–shell nanoparticle was designed and prepared successfully. The core–shell nanoparticle was assembled from two parts including folate and azobenzene surface modified mesoporous silica shell and up-converting nanocrystal core (UCN). The mesoporous silica shell is used for loading the organic dyes and folate conjugation on the surface of the nanoparticle helps to enhance the cellular uptake of the organic dyes. The UCN core works as a transducer to convert near infrared light to visible light to activate the back and forth wagging motion of the azobenzene molecules (azo) on the surface, which will act as a molecular impeller for propelling the release of organic dyes. It can maintain the stability of the fluorescent imaging effect. The experiment results show that with the help of the nanoparticle, cell uptake efficiency of the model dyes Rhodamine and (4′,6-diamidino-2-phenylindole) (DAPI) were significantly improved. The dyes release can only be triggered by NIR exposure and the amount of the released dyes is highly dependent on the duration time of NIR exposure, thus realizing NIR light-regulated precise dyes release. In the live cell imaging test, compared with the pure organic dyes, the fluorescence intensity and stability of live cells were significantly increased after using UCN@mSiO2-(FA and Azo) core–shell nanoparticle for delivering the dyes. Our data suggest that with the development of cell engineering,
with disulfiram, which effectively induce apoptosis in tumor cells. Thus, the elevated tumor copper concentration may be exploited for tumor-targeted cancer chemotherapy. Herein, we report a series of water-soluble poly(ethylene glycol)-block– poly(dithiocarbamate) (PEG–PDTC) copolymers (Figure 1, a). The polymer itself had very low cytotoxicity. Addition of copper(II) ions to the PEG–PDTC solutions induced the formation of nanoparticles (Figure 1, b). Compared with the noncytotoxic PEG–PDTC, the PEG–PDTC/Cu2 + nanoparticles exhibited significantly enhanced cytotoxicity against tumor cells (Figure 1, c). The structure–cytotoxicity correlation and the in vivo anticancer activity of the polymers without or with copper ions were studied.
471
bioavailability. Polymorphic transformation would most probably happen during the good-solvent involved recrystallization in tablet preparation. http://dx.doi.org/10.1016/j.nano.2015.12.074
Improving the antitumor efficacy of doxorubicin-loaded PEG–PCL copolymer micelles by down-regulating hedgehog pathway Quan Zhou, Xiangrui Liu⁎, Jianbin Tang, Youqing Shen, Center for Bionanoengineering and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China ⁎Corresponding author. E-mail address: [email protected] (X. Liu)
Figure 1. (a) Copper-induced formation of PEG–PDTC/Cu2 + nanoparticles. (b) The hydrodynamic size of PEG2k-PDTC1.4 k nanoparticles. (c) Effect of copper(II) on the cytotoxicity of PEG–PDTC against BCap37 human breast tumor cells for 48 h.
Pancreatic ductal adenocarcinoma cancer (PDAC) is one of the most lethal human cancers because it is resistant to many chemotherapeutic drugs. In PDAC, tumor stroma makes up the bulk of the tumor tissue. Tumor–stroma interaction not only induces tumor invasion and metastasis, but also reduces the sensitivity and restricts the penetration of nano-sized antitumor agents (nano-drugs), leading to the limited antitumor activity. Our research focuses on modulating tumor–stroma interaction for improving antitumor efficacy of nano-drugs. The hedgehog pathway (HH), abnormal activated in most PDAC, is one of the key signaling between the tumor and tumor stroma cells, and plays an important role in the tumor drug resistance (Olive et al 2009). Here we used GDC-0449, a small molecule that targets the hedgehog pathway to reverse the drug resistance caused by the tumor stroma cells. The in vitro tumor– stroma co-culture model and in vivo pancreatic tumor model provide a more reliable evaluation platform and facilitate mechanism studies. Improved antitumor efficacy was observed in both pancreatic tumor models in vitro and in vivo.
http://dx.doi.org/10.1016/j.nano.2015.12.073
This work was supported by the National Key Basic Research Program of China (2014CB931900) and National Natural Science Foundation of China (51390481).
http://dx.doi.org/10.1016/j.nano.2015.12.075 An investigation on the dissolution, bioavailability and polymorphic transformation of nimodipine during size reduction from microscale to nanoscale and tablet preparation Yue Wang, Yi Li, Junbo Gong⁎, Zhenping Wei⁎, Department of Chemical Engineering and Technology, Tianjin University, Tianjin, China ⁎Corresponding authors. E-mail address: [email protected] (Z. Wei) The carrier-free solubilization technologies have been extensively used to improve the oral bioavailability of poorly soluble drugs in the pharmaceutical industry. In addition to its water insolubility, nimodipine (Nim) is a polymorphic compound, while polymorphs are known to give rise to significant differences in dissolution and bioavailability of drug compound. This paper aimed at investigating the effect of particle size reduction from microscale to nanoscale on the in vitro dissolution and in vivo bioavailability of Nim as well as the polymorphic transformation during the preparation of Nim tablets. Anti-solvent precipitation was carried out to prepare the nimodipine microsuspension (Nim-Ms) and subsequent high-pressure homogenization was applied to obtain nimodipine nanosuspension (Nim-Ns). The suspensions were then freeze-dried and compressed into nimodipine microcrystal-based tablets (Nim-MBT) and nanocrystal-based tablets (Nim-NBT), respectively. The crystal forms of Nim in Nim-Ms, Nim-Ns, Nim-MBT and Nim-NBT were analyzed by the XRPD and DSC to investigate the polymorphic transformation. The in vitro dissolution of Nim-MBT and Nim-NBT in five different media and their oral absorption abilities in rabbits were investigated. The average particle sizes of Nim-Ms and Nim-Ns were 8.26 ± 0.05 μm or 713 ± 160.45 nm, respectively. In the preparation of Nim tablets, microprecipitation was the only process where polymorphic transformation happened. The drug releases from Nim-NBT were faster than those from Nim-MBT in all the media used. The bioavailability in term of AUC0 -24h of Nim-NBT in rabbits was 1.41 times that of Nim-MBT after oral administration. These results demonstrate that size reduction for nimodipine could accelerate drug dissolution and improve oral
Cascade-released nanoassembly for cancer drug delivery Sun Xuanronga,b, Shao Shiquna, Shen youqinga,⁎, aCenter for Bionanoengineering and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, PR China., bCollaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, PR China ⁎Corresponding author. E-mail address: [email protected] (S. youqing)
Current nanomedicines crafted to deliver anticancer agents to tumor tissues have not showed therapeutic efficacy as expected since they cannot efficiently accomplish the whole cancer drug delivery process, i.e., circulation in blood, accumulation and penetration into tumor, internalization into tumor cells and intracellular drug release, or the CAPIR cascade in short. Herein, we present a 40 nm liposomal dendrimer nanoassembly, G4.5/DOX/LC-PEG, which consisted of 27 dendrimers aggregating together coated with a pegylated fusogenic lipid layer. The pegylated nanoassembly's lipid layer could interact with the cell membrane, releasing the 5 nm dendrimers into the cytosol for intracellular drug release or into the tumor interstitial space, which could further penetrate deep into tumor tissue, enabling the carried DOX to reach cells remote from blood capillaries. The DOX-loaded nanoassembly circumvented the drug resistance and showed significantly enhanced in vivo antitumor efficacy with minimized side effects. This nanoassembly may be a promising concept integrating the needed properties for nanomedicine with high chemotherapeutic efficacy (Scheme 1).
This work was supported by the National Key Basic Research Program of China (2014CB931900) and National Natural Science Foundation of China (51390481).
472
ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575
Antitumor activity of PEG–PCL/dithiocarbamate-copper nanoparticles Chunwan You, Shiqun Shao, Jianbin Tang, Xiangrui Liu, Youqing Shen⁎, Center for Bionanoengineering and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, China ⁎Corresponding author. E-mail address: [email protected] (Y. Shen)
Scheme 1. The nanoassembly G4.5LC-PEG/DOX structure: the dendrimers were self-assembled with DOPE and DSPE-PEG lipids as well as cholesterol to form the nanoassembly with a dendrimer core and lipidic shell. This nanoassembly G4.5LC-PEG/DOX showed deep penetration ability and exhibited strong antitumor activity than corresponding agents PEG–PCL/DOX in MCF7-ADR tumor model.
http://dx.doi.org/10.1016/j.nano.2015.12.076
A dual fluorescent prodrug for in vivo tumor imaging and therapy Minghzou Yea, Xiaohang Wangb, Jianbin Tanga,⁎, Zhiqian Guob,⁎, He Tianb, Weihong Zhub,⁎, Youqing Shena, aKey Laboratory of Biomass Chemical Engineering of Ministry of Education and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, China., bInstitute of Fine Chemicals, East China University of Science and Technology, Shanghai, P.R. China ⁎Corresponding authors. E-mail addresses: [email protected] (M. Ye), [email protected] (J. Tang) Meeting the avid demands for improved chemotherapies, GSH triggered theranostic prodrugs have been prosperously developed in the past decade. Owing to the significant GSH concentration differences between cytosol and extracellular fluids, the rational of the designed structures is to keep stable in circulating system but achieve rapid drug release in cells, especially tumor cells. It has been demonstrated by switchable fluorescent prodrugs. However, most of these prodrugs were plagued by their mono-fluorescent channel and short wavelengths, which were insufficient for describing the overall pharmacokinetics, and also severely interfered by tissue autofluorescence. To solve the problem, we linked an NIR dye and anticancer drug CPT using disulfide bond to develop a novel theranostic prodrug with dualfluorescent channels. The prodrug with intact structure emitted fluorescent of 825 nm, but once cleaved by GSH, the fluorescent emission at 650 nm was switched and simultaneous released a CPT drug, which exhibited an enhanced cytotoxicity. The release process and cytotoxicity of the prodrug nanoparticles were carefully examined in vitro, and it was employed to in situ trace the in vivo activation process on xenograft nude mice model. The results demonstrated the structure to be a promising prodrug for both diagnose and therapy.
Figure 1. In vivo imaging (A) and antitumor activities (B) of the theranostic prodrug on xenograft nude mice.
This work was supported by the National Key Basic Research Program of China (2014CB931900) and National Natural Science Foundation of China (51390481).
http://dx.doi.org/10.1016/j.nano.2015.12.077
Many copper complexes have been shown to be effective inhibitors of tumor angiogenesis. Pyrrolidine dithiocarbamate (PDTC) can complex with copper ions, forming an effective inhibitor of NF-κB activation inhibiting VEGF expression, tumor angiogenesis and growth. We synthesized a series of dithiocarbamate compounds (DTCs) similar to PDTC, and discovered new dithiocarbamates which had much higher efficacy in suppression of tumor growth and metastasis. We found that some DTCs could sequestrate the plasma copper owing to their strong copper binding ability. Interestingly, one of the DTC-copper complexes exhibited 40000 times higher cytotoxicity than DTCs themselves with an IC50 as low as 0.15 nM to Bcap37 cancer cells. Hence, DTC-copper complexes may be new potent antitumor drugs. As the complexes are generally water-insoluble, polymer micelles of polyethylene glycol-polycaprolactone (PEG–PCL) were furthermore used to deliver the complexes for intravenous administration. The DTC-copper complexes could be loaded into PEG5K–PCL4.5K micelles with a size of about 76.8 nm. The PEG–PCL/DTC-copper complex micelles showed a slightly reduced cytotoxicity estimated by MTT assay to the breast cell lines, Bcap-37 and MCF7/ADR. Anticancer effect in vivo and antitumor mechanism of the PEG–PCL/DTC-copper complex NPs will be further studied. This work was supported by the National Key Basic Research Program of China (2014CB931900) and National Natural Science Foundation of China (51390481).
http://dx.doi.org/10.1016/j.nano.2015.12.078
A NIR-remote controlled recyclable up-converting nanoparticle: An improved tool for live cell dye-labeling Bin Zheng, Xiaoqun Gong, Linsu, Sheng Wang, Hanjie Wang⁎, Jin Chang, School of Life Sciences, Tianjin University, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, P.R. China ⁎Corresponding author. E-mail addresses: [email protected] (H. Wang), [email protected] (J. Chang) Due to the selective permeability and complicated cellular environment of live cells, it can easily lead to the low cell uptake efficiency and easy fluorescence decay of organic dyes during the dye-labeling in live cells, which will eventually result in the poor fluorescent imaging. In this work, a protocol of UCN@mSiO2-(FA and Azo) core–shell nanoparticle was designed and prepared successfully. The core–shell nanoparticle was assembled from two parts including folate and azobenzene surface modified mesoporous silica shell and up-converting nanocrystal core (UCN). The mesoporous silica shell is used for loading the organic dyes and folate conjugation on the surface of the nanoparticle helps to enhance the cellular uptake of the organic dyes. The UCN core works as a transducer to convert near infrared light to visible light to activate the back and forth wagging motion of the azobenzene molecules (azo) on the surface, which will act as a molecular impeller for propelling the release of organic dyes. It can maintain the stability of the fluorescent imaging effect. The experiment results show that with the help of the nanoparticle, cell uptake efficiency of the model dyes Rhodamine and (4′,6-diamidino-2-phenylindole) (DAPI) were significantly improved. The dyes release can only be triggered by NIR exposure and the amount of the released dyes is highly dependent on the duration time of NIR exposure, thus realizing NIR light-regulated precise dyes release. In the live cell imaging test, compared with the pure organic dyes, the fluorescence intensity and stability of live cells were significantly increased after using UCN@mSiO2-(FA and Azo) core–shell nanoparticle for delivering the dyes. Our data suggest that with the development of cell engineering,