- Email: [email protected]
Zwitterioinic carboxybetaine polymer based nano drug vehicles
ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575
573
at 60 min (Figure 1, C). After immersing for 30 min, C6-NCs were replaced by fresh medium. Zebrafish were collected and processed at different times up to 48 h. As shown in Figure 1, D, C6-NCs were significantly uptaken by zebrafish with clear regions of strong fluorescence in the eye, gall bladder, intestine and brain. C6-NCs were readily absorbed and distributed in zebrafish but eliminated very slowly. After 48 h, there was still a part of C6 accumulated in the zebrafish body, especially in the digestive system. These findings suggest that nanocrystals could enhance in-vivo absorption and biodistribution of C6 compared to the free drug. In conclusion, zebrafish could be developed as a useful in-vivo model for preliminary and rapid evaluation the absorption and biodistribution of the nanosized formulation. A
200 ng/ml
100 ng/ml
400 ng/ml
800 ng/ml
D
C6-NCs
500
200 ng/ml
300
400 ng/ml
200
N.D.
C6 suspension
(6)
(1) 200
800 ng/ml
100 0
300
C
100 ng/ml
400
ng/mg
ng/mg
B Control
100 0
C6-NCs
5 min 15 min30 min60 min
(2)
(3) (4)
(5)
Figure 1. (A) In-vivo fluorescence imaging of zebrafish with C6-NCs at different concentrations. (B) Uptake efficiency of zebrafish whole body after 30 min incubation with C6-NCs. (C) Uptake efficiency of zebrafish whole body at different time intervals. (D) Bright field and fluorescence microscopy images of zebrafish incubated with C6-NCs for 30 min. (1) brain, (2) eye, (3) gall bladder, (4) bile ducts and liver, (5) intestine, (6) iridophores.
http://dx.doi.org/10.1016/j.nano.2015.12.352 Figure 1. Schematic drawing of consecutive ATRP and redox polymerization assisted DNA detection (up); Photoimage and thickness of polymer growth at the spot of DNA sequences on Au substrate (down).
http://dx.doi.org/10.1016/j.nano.2015.12.351
Zebrafish: An in-vivo model to evaluate absorption and biodistribution of nanocrystals Ye Lia, Xiaoqing Miaoa, Liang Wanga, Xiang Yib, Simon M.Y. Leea, Ying Zhenga, a State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China, bDivision of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, USA E-mail address: [email protected] (Y. Zheng) Nanosized molecules possess enormous potential in imaging and therapeutic treatment. Due to their special physiochemical properties, their in-vivo behavior including absorption and biodistribution is worth to be studied. Zebrafish have emerged as useful vertebrate models for the optical tracking and biocompatibility assessment because of their transparent body and similar homology to human. This study aimed to explore the absorption and biodistribution of nanocrystals in zebrafish model. A highly lipophilic compound named coumarin-6 (C6) was selected and formulated as C6nanocrystals (C6-NCs) by anti-solvent precipitation method with an average particle size of 67.5 ± 5.2 nm. Larval zebrafish at 8 days post-fertilization were incubated with different concentrations of C6-NCs.Whole body of zebrafish was collected from 5 to 60 min to take fluorescence images. C6 was also extracted and quantified by florescence detector. As shown in Figure 1, A, no obvious fluorescence was observed in C6 suspension treated group, while strong fluorescence was observed in C6-NCs treated group, and the intensity of fluorescence emission increased at dose dependent manner. Above result was consistent with the quantification result shown in Figure 1, B. The concentration of C6 increased from 5 min to 30 min and reached to a plateau
We acknowledge research funding from the University of Macau (Research Grant MYRG 112(Y2-L3)-ICMS13-ZY).
Zwitterioinic carboxybetaine polymer based nano drug vehicles Zhen Wang, Juan Zhang, Weifeng Lin, Shengfu Chen, Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, China E-mail address: [email protected] (S. Chen) While polyethylene glycol (PEG) is the most commonly used material in nano drug vehicles (NDVs) to prevent the adsorption of proteins, lower the phagocytosis into macrophage cells, evade recognition by the reticuloendothelial system, and thus increase the circulation time, zwitterionic polymers are excellent alternatives due to the excellent resistance to protein adsorption, functioanlization, chemical/biological stability over PEG. The recent advances in zwitterionic polymers for drug delivery draw much attention in research community. Recently, we investigated the performances of zwitterionic polymers related NDVs, which included novel PCBMAEEPCBMA copolymer with hydrolytic and zwitterionic blocks for high and stable gene transfection in complex medium, and surface protonation/deprotonation controlled instant affinity switch of NDVs for pH triggered tumor cell targeting. Results shown both NDVs show excellent performance in highly complex medium, serum. The PCBMAEE-PCBMA copolymer based gene transfection vectors showed 1) around 27-folder higher luciferase expression than the PEI 25 kDa in serum free medium; 2) the high gene transfection rates of the PCBMAEE50-PCBMAn/pEGFP complexes near 70% and 56% in both serum-free and 10% serum growth medium, respectively; and 3) luciferase expression maintained around 25% of standard-dosage transfection when 1/20 standard dosage was used, whereas PEI 25 kDa reduced to its 2%, only 1/230 of the luciferase expression of the PCBMAEE50-PCBMAn/pEGFP complexes. Moreover, the instantly affinity-switchable NDV targeting to poly sialic acid (PSA) on tumor cell at physiologically related pH range from pH 7.4 to 6.8, the lower extracellular pH found in malignant tumors, can be controlled by the amount of the strong acid co-monomer. With strong acid groups near the hydrophobic core, the outmost layer of carboxyl group will be protonated and switched to high affinity groups to PSA in response to pH change, which promotes the affinity to the tumor cell and the internalization of CBNDVs by tumor cells. This CB based delivery system that is sensitive to the acidic tumor microenvironment has the ability to reduce the need for compromise between faster internalization and enhanced hemocompatibility of NDVs as seen with
574
ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575
PEG-based systems and therefore has great potential for the systemic delivery of therapeutics for improved cancer treatment. http://dx.doi.org/10.1016/j.nano.2015.12.353
Zwitterionic theranostic micelles based on brush-shaped amphiphilic homopolymer Yangjun Chen, Qiao Jin, Jian Ji, MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, China E-mail addresses: [email protected] (Q. Jin), [email protected] (J. Ji) Theranostics, a cancer treatment strategy which integrates therapeutics and diagnostics, has been actively studied for years due to its increased drug efficacy as well as allowance for real-time therapeutic response monitoring. Near-infrared (NIR) fluorescence dyes are among the best candidates; they offer not only better sensitivity for in vivo detection, but also high efficiency and minimal invasiveness based on NIR photothermal therapy. IR-780 iodide is a lipophilic cation heptamethine dye with higher fluorescence intensity and more stable than indocyanine green (ICG), the FDA approved clinical imaging agent. However, its poor aqueous stability, rapid elimination from the body, and lack of target specificity limited its further biomedical applications. Polymer micelles have been extensively studied to encapsulate hydrophobic drugs/dyes and the nanoscaled structure improves tumor accumulation. However, conventional multimolecular micelles suffer from insufficient stability upon dilution in the bloodstream, leading to a burst release of drug and loss of tumor-targeting capability. Unimolecular micelles with a core–shell structure have been developed and they can maintain excellent micellar stability because they are formed by individual multiarm amphiphilic copolymer molecules consisting of only covalent bonds. Unimolecular micelles formed by brush-shaped amphiphilic copolymers, especially brush homopolymers, are of great interest and still under study. Here in this work, we synthesized a zwitterionic amphiphilic homopolymer (PMDPC) via addition –fragmentation chain transfer (RAFT) polymerization, and evaluated its application for the encapsulation of IR780. The photothermal effect and photothermal cytoxicity to HepG2 cancer cells of IR-780 encapsulated PMDPC micelles (PMDPC/IR-780) were studied. In vivo imaging results suggested that a higher accumulation of PMDPC/IR-780 than that of free IR-780 in tumor site was verified and thus the tumor could be detected via fluorescence imaging. Therefore, the IR-780 loaded zwitterionic unimolecular micelles could have great potential for cancer theranostics.
Scheme 1. Schematic illustration of zwitterionic theranostic micelles based on brush-shaped amphiphilic homopolymer.
and PEG (Tf-PEG-RuNPs); transferrin was employed as a targeting tumor cells agent. As expected, the Tf modification could significantly enhance the cellular uptake through endocytosis. Meanwhile, cytotoxicity experiments showed that three human cancer cell lines were susceptible to Tf-PEG-RuNPs with IC50 values ranging from 7.3 to 40.5 μg/ml. It is noteworthy that the Tf-PEG-RuNPs is more toxic than cisplatin against A549 cells. Furthermore, the study of Tf-PEG-RuNPs induced A549 cells apoptosis mechanism indicated that Tf-PEG-RuNPs reducing the mitochondrial membrane potential and increasing the levels of ROS (reactive oxygen species). All results suggest that RuNPs modified by Tf and PEG may be a considerable nanomedicine for human cancer treatment. Herein we report novel cancer-targeted Ru nanoparticles based on Tf and PEG conjugated RuNPs, in which Tf-PEG-RuNPs could enhance cellular uptake and anticancer efficacy. The in vitro anticancer activity of Tf-PEG-RuNPs and the underlying molecular mechanisms were also investigated in this study. Our results showed that Tf surface decoration significantly enhanced the cellular uptake of RuNPs through caveolae-mediated and clathrin-mediated endocytosis in cancer cells, and increased their selectivity between cancer and normal cells. Furthermore, deeper anticancer mechanisms studies showed that Tf-PEG-RuNPs induced apoptosis through the mitochondria-mediated pathway and dependent on ROS generation. This cancer-targeted design of RuNPs opens a new path for synergistic treating of cancer with higher efficacy and decreased side effects. http://dx.doi.org/10.1016/j.nano.2015.12.355
Magnetic targeting of human mesenchymal stem cells with internalized γ-Fe2O3@Ru nanoparticles for differentiation and MRI tracking Ying Liu, Yanan Liu, Chuping Zheng, Xianbo Zhou, Jie Liu⁎, Department of Chemistry, Jinan University, Guangzhou, China ⁎Corresponding author. E-mail address: [email protected] (J. Liu) The culture of human mesenchymal stem cells (MSCs), due to their ability for successive passages and multilineage differentiation, is a very important part of tissue engineering, which has attracted substantial attention in stem cell therapy. Iron oxides were used to label stem cells for magnetic resonance imaging study. However, direct evidence of cytotoxicity and the effect of differentiation for MSCs labeled with magnetic nanocomposites have not been confidently established. In this study, Ru nanoparticles (RuNPs), γ-Fe2O3@Ru nanoparticles (Fe2O3@Ru) and γ-Fe2O3@Se nanoparticles (Fe2O3@Se) were synthesized, and these particles were nontoxic to MSCs based on cytotoxicity assays. Fe2O3@Ru and Fe2O3@Se were distributed around the nucleus of the MSCs as a spherical shell. We demonstrate that RuNPs, Fe2O3@Ru and Fe2O3@Se could induce MSCs to differentiate into osteoblasts, and in particular, Fe2O3@Ru was highly significant for promoting the osteogenic differentiation of MSCs and inhibiting adipocytic differentiation, which may be related to intracellular iron particles. We confirmed that the promotion of the osteogenic differentiation of MSCs might be regulated by a Smad-dependent bone morphogenetic protein (BMP) signaling pathway. We also indicated that the BMP signaling pathway is related to the Fe2O3@Ru–MSC interaction. The results revealed that Fe2O3@Ru-treated MSCs succeeded in expressing MSC surface markers.
http://dx.doi.org/10.1016/j.nano.2015.12.354
Transferrin modified Ru nanoparticles inhibit tumor cells by enhancing cellular uptake and regulation of reactive oxygen Chengwen Cao, Shuang Zhao, Qianqian Yu, Yanan Liu, Yanhui Zhou, Jie Liu⁎, Department of Chemistry, Jinan University, Guangzhou, China ⁎Corresponding author. E-mail address: [email protected] (J. Liu) In the past two decades, many kinds of ruthenium complexes have been synthetized and their bioactivity was investigated, especially antitumor effect. In this work, we designed and synthetized Ru nanoparticles modified by transferrin
http://dx.doi.org/10.1016/j.nano.2015.12.356
573
at 60 min (Figure 1, C). After immersing for 30 min, C6-NCs were replaced by fresh medium. Zebrafish were collected and processed at different times up to 48 h. As shown in Figure 1, D, C6-NCs were significantly uptaken by zebrafish with clear regions of strong fluorescence in the eye, gall bladder, intestine and brain. C6-NCs were readily absorbed and distributed in zebrafish but eliminated very slowly. After 48 h, there was still a part of C6 accumulated in the zebrafish body, especially in the digestive system. These findings suggest that nanocrystals could enhance in-vivo absorption and biodistribution of C6 compared to the free drug. In conclusion, zebrafish could be developed as a useful in-vivo model for preliminary and rapid evaluation the absorption and biodistribution of the nanosized formulation. A
200 ng/ml
100 ng/ml
400 ng/ml
800 ng/ml
D
C6-NCs
500
200 ng/ml
300
400 ng/ml
200
N.D.
C6 suspension
(6)
(1) 200
800 ng/ml
100 0
300
C
100 ng/ml
400
ng/mg
ng/mg
B Control
100 0
C6-NCs
5 min 15 min30 min60 min
(2)
(3) (4)
(5)
Figure 1. (A) In-vivo fluorescence imaging of zebrafish with C6-NCs at different concentrations. (B) Uptake efficiency of zebrafish whole body after 30 min incubation with C6-NCs. (C) Uptake efficiency of zebrafish whole body at different time intervals. (D) Bright field and fluorescence microscopy images of zebrafish incubated with C6-NCs for 30 min. (1) brain, (2) eye, (3) gall bladder, (4) bile ducts and liver, (5) intestine, (6) iridophores.
http://dx.doi.org/10.1016/j.nano.2015.12.352 Figure 1. Schematic drawing of consecutive ATRP and redox polymerization assisted DNA detection (up); Photoimage and thickness of polymer growth at the spot of DNA sequences on Au substrate (down).
http://dx.doi.org/10.1016/j.nano.2015.12.351
Zebrafish: An in-vivo model to evaluate absorption and biodistribution of nanocrystals Ye Lia, Xiaoqing Miaoa, Liang Wanga, Xiang Yib, Simon M.Y. Leea, Ying Zhenga, a State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China, bDivision of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, USA E-mail address: [email protected] (Y. Zheng) Nanosized molecules possess enormous potential in imaging and therapeutic treatment. Due to their special physiochemical properties, their in-vivo behavior including absorption and biodistribution is worth to be studied. Zebrafish have emerged as useful vertebrate models for the optical tracking and biocompatibility assessment because of their transparent body and similar homology to human. This study aimed to explore the absorption and biodistribution of nanocrystals in zebrafish model. A highly lipophilic compound named coumarin-6 (C6) was selected and formulated as C6nanocrystals (C6-NCs) by anti-solvent precipitation method with an average particle size of 67.5 ± 5.2 nm. Larval zebrafish at 8 days post-fertilization were incubated with different concentrations of C6-NCs.Whole body of zebrafish was collected from 5 to 60 min to take fluorescence images. C6 was also extracted and quantified by florescence detector. As shown in Figure 1, A, no obvious fluorescence was observed in C6 suspension treated group, while strong fluorescence was observed in C6-NCs treated group, and the intensity of fluorescence emission increased at dose dependent manner. Above result was consistent with the quantification result shown in Figure 1, B. The concentration of C6 increased from 5 min to 30 min and reached to a plateau
We acknowledge research funding from the University of Macau (Research Grant MYRG 112(Y2-L3)-ICMS13-ZY).
Zwitterioinic carboxybetaine polymer based nano drug vehicles Zhen Wang, Juan Zhang, Weifeng Lin, Shengfu Chen, Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, China E-mail address: [email protected] (S. Chen) While polyethylene glycol (PEG) is the most commonly used material in nano drug vehicles (NDVs) to prevent the adsorption of proteins, lower the phagocytosis into macrophage cells, evade recognition by the reticuloendothelial system, and thus increase the circulation time, zwitterionic polymers are excellent alternatives due to the excellent resistance to protein adsorption, functioanlization, chemical/biological stability over PEG. The recent advances in zwitterionic polymers for drug delivery draw much attention in research community. Recently, we investigated the performances of zwitterionic polymers related NDVs, which included novel PCBMAEEPCBMA copolymer with hydrolytic and zwitterionic blocks for high and stable gene transfection in complex medium, and surface protonation/deprotonation controlled instant affinity switch of NDVs for pH triggered tumor cell targeting. Results shown both NDVs show excellent performance in highly complex medium, serum. The PCBMAEE-PCBMA copolymer based gene transfection vectors showed 1) around 27-folder higher luciferase expression than the PEI 25 kDa in serum free medium; 2) the high gene transfection rates of the PCBMAEE50-PCBMAn/pEGFP complexes near 70% and 56% in both serum-free and 10% serum growth medium, respectively; and 3) luciferase expression maintained around 25% of standard-dosage transfection when 1/20 standard dosage was used, whereas PEI 25 kDa reduced to its 2%, only 1/230 of the luciferase expression of the PCBMAEE50-PCBMAn/pEGFP complexes. Moreover, the instantly affinity-switchable NDV targeting to poly sialic acid (PSA) on tumor cell at physiologically related pH range from pH 7.4 to 6.8, the lower extracellular pH found in malignant tumors, can be controlled by the amount of the strong acid co-monomer. With strong acid groups near the hydrophobic core, the outmost layer of carboxyl group will be protonated and switched to high affinity groups to PSA in response to pH change, which promotes the affinity to the tumor cell and the internalization of CBNDVs by tumor cells. This CB based delivery system that is sensitive to the acidic tumor microenvironment has the ability to reduce the need for compromise between faster internalization and enhanced hemocompatibility of NDVs as seen with
574
ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575
PEG-based systems and therefore has great potential for the systemic delivery of therapeutics for improved cancer treatment. http://dx.doi.org/10.1016/j.nano.2015.12.353
Zwitterionic theranostic micelles based on brush-shaped amphiphilic homopolymer Yangjun Chen, Qiao Jin, Jian Ji, MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, China E-mail addresses: [email protected] (Q. Jin), [email protected] (J. Ji) Theranostics, a cancer treatment strategy which integrates therapeutics and diagnostics, has been actively studied for years due to its increased drug efficacy as well as allowance for real-time therapeutic response monitoring. Near-infrared (NIR) fluorescence dyes are among the best candidates; they offer not only better sensitivity for in vivo detection, but also high efficiency and minimal invasiveness based on NIR photothermal therapy. IR-780 iodide is a lipophilic cation heptamethine dye with higher fluorescence intensity and more stable than indocyanine green (ICG), the FDA approved clinical imaging agent. However, its poor aqueous stability, rapid elimination from the body, and lack of target specificity limited its further biomedical applications. Polymer micelles have been extensively studied to encapsulate hydrophobic drugs/dyes and the nanoscaled structure improves tumor accumulation. However, conventional multimolecular micelles suffer from insufficient stability upon dilution in the bloodstream, leading to a burst release of drug and loss of tumor-targeting capability. Unimolecular micelles with a core–shell structure have been developed and they can maintain excellent micellar stability because they are formed by individual multiarm amphiphilic copolymer molecules consisting of only covalent bonds. Unimolecular micelles formed by brush-shaped amphiphilic copolymers, especially brush homopolymers, are of great interest and still under study. Here in this work, we synthesized a zwitterionic amphiphilic homopolymer (PMDPC) via addition –fragmentation chain transfer (RAFT) polymerization, and evaluated its application for the encapsulation of IR780. The photothermal effect and photothermal cytoxicity to HepG2 cancer cells of IR-780 encapsulated PMDPC micelles (PMDPC/IR-780) were studied. In vivo imaging results suggested that a higher accumulation of PMDPC/IR-780 than that of free IR-780 in tumor site was verified and thus the tumor could be detected via fluorescence imaging. Therefore, the IR-780 loaded zwitterionic unimolecular micelles could have great potential for cancer theranostics.
Scheme 1. Schematic illustration of zwitterionic theranostic micelles based on brush-shaped amphiphilic homopolymer.
and PEG (Tf-PEG-RuNPs); transferrin was employed as a targeting tumor cells agent. As expected, the Tf modification could significantly enhance the cellular uptake through endocytosis. Meanwhile, cytotoxicity experiments showed that three human cancer cell lines were susceptible to Tf-PEG-RuNPs with IC50 values ranging from 7.3 to 40.5 μg/ml. It is noteworthy that the Tf-PEG-RuNPs is more toxic than cisplatin against A549 cells. Furthermore, the study of Tf-PEG-RuNPs induced A549 cells apoptosis mechanism indicated that Tf-PEG-RuNPs reducing the mitochondrial membrane potential and increasing the levels of ROS (reactive oxygen species). All results suggest that RuNPs modified by Tf and PEG may be a considerable nanomedicine for human cancer treatment. Herein we report novel cancer-targeted Ru nanoparticles based on Tf and PEG conjugated RuNPs, in which Tf-PEG-RuNPs could enhance cellular uptake and anticancer efficacy. The in vitro anticancer activity of Tf-PEG-RuNPs and the underlying molecular mechanisms were also investigated in this study. Our results showed that Tf surface decoration significantly enhanced the cellular uptake of RuNPs through caveolae-mediated and clathrin-mediated endocytosis in cancer cells, and increased their selectivity between cancer and normal cells. Furthermore, deeper anticancer mechanisms studies showed that Tf-PEG-RuNPs induced apoptosis through the mitochondria-mediated pathway and dependent on ROS generation. This cancer-targeted design of RuNPs opens a new path for synergistic treating of cancer with higher efficacy and decreased side effects. http://dx.doi.org/10.1016/j.nano.2015.12.355
Magnetic targeting of human mesenchymal stem cells with internalized γ-Fe2O3@Ru nanoparticles for differentiation and MRI tracking Ying Liu, Yanan Liu, Chuping Zheng, Xianbo Zhou, Jie Liu⁎, Department of Chemistry, Jinan University, Guangzhou, China ⁎Corresponding author. E-mail address: [email protected] (J. Liu) The culture of human mesenchymal stem cells (MSCs), due to their ability for successive passages and multilineage differentiation, is a very important part of tissue engineering, which has attracted substantial attention in stem cell therapy. Iron oxides were used to label stem cells for magnetic resonance imaging study. However, direct evidence of cytotoxicity and the effect of differentiation for MSCs labeled with magnetic nanocomposites have not been confidently established. In this study, Ru nanoparticles (RuNPs), γ-Fe2O3@Ru nanoparticles (Fe2O3@Ru) and γ-Fe2O3@Se nanoparticles (Fe2O3@Se) were synthesized, and these particles were nontoxic to MSCs based on cytotoxicity assays. Fe2O3@Ru and Fe2O3@Se were distributed around the nucleus of the MSCs as a spherical shell. We demonstrate that RuNPs, Fe2O3@Ru and Fe2O3@Se could induce MSCs to differentiate into osteoblasts, and in particular, Fe2O3@Ru was highly significant for promoting the osteogenic differentiation of MSCs and inhibiting adipocytic differentiation, which may be related to intracellular iron particles. We confirmed that the promotion of the osteogenic differentiation of MSCs might be regulated by a Smad-dependent bone morphogenetic protein (BMP) signaling pathway. We also indicated that the BMP signaling pathway is related to the Fe2O3@Ru–MSC interaction. The results revealed that Fe2O3@Ru-treated MSCs succeeded in expressing MSC surface markers.
http://dx.doi.org/10.1016/j.nano.2015.12.354
Transferrin modified Ru nanoparticles inhibit tumor cells by enhancing cellular uptake and regulation of reactive oxygen Chengwen Cao, Shuang Zhao, Qianqian Yu, Yanan Liu, Yanhui Zhou, Jie Liu⁎, Department of Chemistry, Jinan University, Guangzhou, China ⁎Corresponding author. E-mail address: [email protected] (J. Liu) In the past two decades, many kinds of ruthenium complexes have been synthetized and their bioactivity was investigated, especially antitumor effect. In this work, we designed and synthetized Ru nanoparticles modified by transferrin
http://dx.doi.org/10.1016/j.nano.2015.12.356