- Email: [email protected]
TPP-modified protein-polymer bioconjugate as a mitochondria-targeting nanocarrier
Abstracts / Journal of Controlled Release 259 (2017) e5–e195
microenvironment, the ketal linkers could be hydrolyzed leading to the release of Cy5.5 from the surface of the GNRs thus retrieving its fluorescence. Moreover, upon the irradiation of the NIR laser, the GNRs could generate heat and consequently enhance the photoacoustic signal resulting in the death of cancer cells (Fig. 1). The fluorescence spectrophotometer was used to determine the fluorescence change of Cy5.5, which was quenched perfectly by GNRs when covalently attached, and was recovered under mild acidic environment. The fluorescence/photoacoustic property and the photothermal therapy ability of the nanoprobes were systematically investigated in vitro and in vivo.
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of ca. 90 nm, bright green fluoresence and high serum stability from hyaluronic acid-cystamine-tetrazole and reductively degradable polyiodixanol-methacrylate via nanoprecipitation and a photo-click crosslinking reaction. Notably, paclitaxel (PTX)-loaded HAI-NGs showed a fast glutathione-responsive drug release. Confocal microscopy displayed efficient uptake of HAI-NGs by CD44 overexpressing MCF-7 cells via a receptor-mediated mechanism. The in vivo pharmcokinetics, near-infrared imaging and biodistribution studies revealed that HAI-NGs significantly prolonged the blood circulation time and enhanced tumor accumulation of PTX. Interestingly, significantly enhanced CT imaging was observed for MCF-7 breast tumors in nude mice via either intratumoral or intravenous injection of HAI-NGs as compared to iodixanol (Fig. 1). HAI-NGs fluoresence was distributed thoughout the whole tumor indicating deep tumor penetration. PTX-loaded HAI-NGs showed effective suppression of tumor growth with little systemic toxicity. HAI-NGs appear as a “smart” theranostic nanoplatform for the treatment of CD44 positive tumors.
Fig. 1. Schematic illustration of GNRs-based nanoprobes for pH-sensitive tumor imaging and therapy.
Keywords: pH-sensitive, folate receptor-targeting, gold nanorods, photoacoustic imaging, photothermal therapy Acknowledgements We thank the financial support from the National Natural Science Foundation of China (Grants 21476077, 21236002) and Shanghai Pujiang Program. References [1] X. Zhang, Y. Lin, R. J. Gillies, Tumor pH and its measurement, J. Nucl. Med. 51 (2010) 1167-1170. [2] L. Wang, C. Li, pH responsive fluorescence nanoprobe imaging of tumors by sensing the acidic microenvironment, J. Mater. Chem. 21 (2011) 15862-15871.
doi:10.1016/j.jconrel.2017.03.335
Reduction-sensitive nanogels based on HA and iodixanol for both tumor-targeted CT imaging and therapy Yaqin Zhua,b, Jian Zhanga, Jan Feijenb,⁎, Zhiyuan Zhonga,⁎ a Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China b Department of Polymer Chemistry and Biomaterials, Faculty of Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands ⁎Corresponding authors. E-mail addresses: [email protected] (Y. Zhu), [email protected] (J. Feijen), [email protected] (Z. Zhong) In recent years, nanosized CT contrast agents have attracted great interest as they have several advantages over small molecular contrast agents such as prolonged circulation time, site-specific accumulation and use for theranostics [1]. Here, we designed hyaluronic acid-iodixanol nanogels (HAI-NGs) for targeted X-ray computed tomography (CT) imaging and chemotherapy of MCF-7 human breast tumors [2]. HAI-NGs were obtained with a small size
Fig. 1. (A) HU measurements of HAI-NGs. (B) three-dimensional reconstructed CT images of the MCF-7 tumor bearing mice following intratumoral (i.t.) injection of HAINGs at a concentration of 15 mg/mL (60 mg iodine equiv./kg). Circled areas indicate the location of the tumor.
Keywords: nanogels, hyaluronic acid, X-ray computed tomography, reduction-sensitive, paclitaxel Acknowledgements This work is supported by research grants from the National Natural Science Foundation of China (NSFC 51273139, 51273137 and 51473110). References [1] T. Lammers, S. Aime, W.E. Hennink, G. Storm, F. Kiessling, Theranostic nanomedicine, Acc. Chem. Res. 44 (2011) 1029-1038. [2] Y. Zhu, X. Wang, J. Chen, J. Zhang, F. Meng, C. Deng, R. Cheng, J. Feijen, Z. Zhong, Bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels for targeted X-ray computed tomography imaging and chemotherapy of breast tumors, J. Control. Release 244 (2016) 229-239.
doi:10.1016/j.jconrel.2017.03.336
TPP-modified protein-polymer bioconjugate as a mitochondria-targeting nanocarrier Guiyang Zhanga, Guhuan Liub, Ye Zhanga, Manqing Yana, Hong Bia,⁎ a College of Chemistry and Chemical Engineering, Anhui University, Hefei 230601, China b Department of Polymer Science and Engineering, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, China
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Abstracts / Journal of Controlled Release 259 (2017) e5–e195
⁎Corresponding author. E-mail addresses: [email protected] (Y. Zhang), [email protected] (H. Bi)
Mitochondria-targeted nanocarriers using hyperbranched polycations wrapped carbon nanotubes for augment photodynamic therapeutic effects
In recent years, the self-assembled nanostructures of biomolecules, especially the ones based on protein or DNA, have been attracted much attention in the field of nanomedicine [1]. On the other hand, mitochondrion has emerged as an important site-specific target for therapeutic and imaging purposes [2]. In our previous work, a mitochondria-targeting bionanoplatform has been constructed by using lipophilic cation triphenyl phosphonium (TPP) as a targeting molecule [3]. Nevertheless, how to improve the biocompatibility and biodegradability of the mitochondria-targeting bionanoplatform is still a challenge for the design and synthesis of drug delivery nanocarriers. Herein, a biodegradable protein-polymer bioconjugate ended with a TPP group (TPP-PDMA-b-P(DEGMA-co-NBDAE)-BSA) was synthesized, in which a hydrophobic pyridyl disulfide-functionalized copolymer was covalently linked to bovine serum albumin (BSA) through a pyridyl disulfide-sulfhydryl coupling method. The obtained amphiphilic TPP-modified bioconjugate could self-assemble into spherical micelles (Fig. 1). Confocal laser scanning microscopy (CLSM) analysis indicated that the micelles could be uptaken by HeLa cells and selectively localize in mitochondria. Furthermore, the TPP-modified bioconjugates loaded with doxorubicin showed a controlled release behavior, showing the potential applications in mitochondria-targeting drug delivery systems.
Yi Liua,b, Huiru Lub, Aiping Lanb, Yi Hub, Heping Lia,⁎, Jun Chenb,⁎ Key Laboratory of Road Structure and Material of Ministry of Transport, Hunan Provincial Key Laboratory of Materials Protection for Electric Power and Transportation, Changsha University of Science and Technology, Changsha 410114, China b CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, China ⁎Corresponding authors. E-mail addresses: [email protected] (Y. Liu), [email protected] (H. Li), [email protected] (J. Chen) a
Photodynamic therapy (PDT), as a noninvasive therapeutic procedure, has been successfully applied to treat tumors and other diseases. A new generation of photodynamic therapy that precisely functions against diseased cells and cellular organelles, is highly desired to circumvent those limitations in conventional photodynamic therapy (PDT). Herein, we develop a novel nanoplatform based on cationic amphiphilic polymer-wrapped carbon nanotubes (CNTs) and indocyanine green (ICG) for photodynamic therapy (PDT) has been successfully constructed (Fig. 1). The as-prepared nanoparticles exhibited excellent mitochondria targeting due to the synergistic property of highly positive charges on the surface and the highly hydrophobicity in the core [1, 2]. When irradiated upon 808 nm NIR laser in a very limited dose, the CNTs@ICG could precisely damage mitochondria by producing reactive oxygen species (ROS), which further induced the ROS burst release from nanoparticles-targeted mitochondria. The overproduced ROS accumulated in mitochondria ultimately resulted in mitochondrial collapse and irreversible cell apoptosis. In comparison with nontargeting nanoplatform, the enhanced HeLa cells lethality with less dose of the 808 nm laser is observed. Thus the CNTs@ICG can achieve an amplifying photodynamic therapeutic effect on cancer treatment.
Fig. 1. Schematic illustration of the self-assembly of protein-polymer conjugates for mitochondria-targeted drug delivery.
Keywords: self-assembly, BSA, biodegradable polymer, mitochondria targeting, drug delivery Acknowledgement This work was financed by the NSFC under Grant No. 51272002. References [1] M. Vendruscolo, C.M. Dobson, Structural biology: protein self-assembly intermediates. Nat. Chem. Biol. 9 (2013) 216-217. [2] S. Fulda, L. Galluzzi, G. Kroemer, Targeting mitochondria for cancer therapy. Nat. Rev. Drug Discov.9 (2010) 447-464. [3] Y. Zhang, Y.J. Shen, X.Y. Teng, M.Q. Yan, H. Bi, P.C. Morais, Mitochondria-Targeting nanoplatform with fluorescent carbon dots for long time imaging and magnetic fieldenhanced cellular uptake. ACS Appl. Mater. Interface 7 (2015) 10201-10212.
doi:10.1016/j.jconrel.2017.03.337
Fig. 1. Illustration of the preparation of CNTs@ICG nanocomposites and targeting mitochondria for amplifying photodynamic therapeutic effects.
Keywords: carbon nanotube, ICG, mitochondria, reactive oxygen species, photodynamic therapy Acknowledgements This work was supported by the National Natural Science Foundation of China (21304098, 21390411, 21574136), CAS Youth Innovation Promotion Association Program (2015008). References [1] F.F. Zhou, D. Xing, B.Y. Wu, S.N. Wu, Z.M. Ou, W.R. Chen, New insights of transmembranal mechanism and subcellular localization of noncovalently modified single-walled carbon nanotubes, Nano Lett. 10 (2010) 1677-1681.
microenvironment, the ketal linkers could be hydrolyzed leading to the release of Cy5.5 from the surface of the GNRs thus retrieving its fluorescence. Moreover, upon the irradiation of the NIR laser, the GNRs could generate heat and consequently enhance the photoacoustic signal resulting in the death of cancer cells (Fig. 1). The fluorescence spectrophotometer was used to determine the fluorescence change of Cy5.5, which was quenched perfectly by GNRs when covalently attached, and was recovered under mild acidic environment. The fluorescence/photoacoustic property and the photothermal therapy ability of the nanoprobes were systematically investigated in vitro and in vivo.
e169
of ca. 90 nm, bright green fluoresence and high serum stability from hyaluronic acid-cystamine-tetrazole and reductively degradable polyiodixanol-methacrylate via nanoprecipitation and a photo-click crosslinking reaction. Notably, paclitaxel (PTX)-loaded HAI-NGs showed a fast glutathione-responsive drug release. Confocal microscopy displayed efficient uptake of HAI-NGs by CD44 overexpressing MCF-7 cells via a receptor-mediated mechanism. The in vivo pharmcokinetics, near-infrared imaging and biodistribution studies revealed that HAI-NGs significantly prolonged the blood circulation time and enhanced tumor accumulation of PTX. Interestingly, significantly enhanced CT imaging was observed for MCF-7 breast tumors in nude mice via either intratumoral or intravenous injection of HAI-NGs as compared to iodixanol (Fig. 1). HAI-NGs fluoresence was distributed thoughout the whole tumor indicating deep tumor penetration. PTX-loaded HAI-NGs showed effective suppression of tumor growth with little systemic toxicity. HAI-NGs appear as a “smart” theranostic nanoplatform for the treatment of CD44 positive tumors.
Fig. 1. Schematic illustration of GNRs-based nanoprobes for pH-sensitive tumor imaging and therapy.
Keywords: pH-sensitive, folate receptor-targeting, gold nanorods, photoacoustic imaging, photothermal therapy Acknowledgements We thank the financial support from the National Natural Science Foundation of China (Grants 21476077, 21236002) and Shanghai Pujiang Program. References [1] X. Zhang, Y. Lin, R. J. Gillies, Tumor pH and its measurement, J. Nucl. Med. 51 (2010) 1167-1170. [2] L. Wang, C. Li, pH responsive fluorescence nanoprobe imaging of tumors by sensing the acidic microenvironment, J. Mater. Chem. 21 (2011) 15862-15871.
doi:10.1016/j.jconrel.2017.03.335
Reduction-sensitive nanogels based on HA and iodixanol for both tumor-targeted CT imaging and therapy Yaqin Zhua,b, Jian Zhanga, Jan Feijenb,⁎, Zhiyuan Zhonga,⁎ a Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China b Department of Polymer Chemistry and Biomaterials, Faculty of Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands ⁎Corresponding authors. E-mail addresses: [email protected] (Y. Zhu), [email protected] (J. Feijen), [email protected] (Z. Zhong) In recent years, nanosized CT contrast agents have attracted great interest as they have several advantages over small molecular contrast agents such as prolonged circulation time, site-specific accumulation and use for theranostics [1]. Here, we designed hyaluronic acid-iodixanol nanogels (HAI-NGs) for targeted X-ray computed tomography (CT) imaging and chemotherapy of MCF-7 human breast tumors [2]. HAI-NGs were obtained with a small size
Fig. 1. (A) HU measurements of HAI-NGs. (B) three-dimensional reconstructed CT images of the MCF-7 tumor bearing mice following intratumoral (i.t.) injection of HAINGs at a concentration of 15 mg/mL (60 mg iodine equiv./kg). Circled areas indicate the location of the tumor.
Keywords: nanogels, hyaluronic acid, X-ray computed tomography, reduction-sensitive, paclitaxel Acknowledgements This work is supported by research grants from the National Natural Science Foundation of China (NSFC 51273139, 51273137 and 51473110). References [1] T. Lammers, S. Aime, W.E. Hennink, G. Storm, F. Kiessling, Theranostic nanomedicine, Acc. Chem. Res. 44 (2011) 1029-1038. [2] Y. Zhu, X. Wang, J. Chen, J. Zhang, F. Meng, C. Deng, R. Cheng, J. Feijen, Z. Zhong, Bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels for targeted X-ray computed tomography imaging and chemotherapy of breast tumors, J. Control. Release 244 (2016) 229-239.
doi:10.1016/j.jconrel.2017.03.336
TPP-modified protein-polymer bioconjugate as a mitochondria-targeting nanocarrier Guiyang Zhanga, Guhuan Liub, Ye Zhanga, Manqing Yana, Hong Bia,⁎ a College of Chemistry and Chemical Engineering, Anhui University, Hefei 230601, China b Department of Polymer Science and Engineering, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, China
e170
Abstracts / Journal of Controlled Release 259 (2017) e5–e195
⁎Corresponding author. E-mail addresses: [email protected] (Y. Zhang), [email protected] (H. Bi)
Mitochondria-targeted nanocarriers using hyperbranched polycations wrapped carbon nanotubes for augment photodynamic therapeutic effects
In recent years, the self-assembled nanostructures of biomolecules, especially the ones based on protein or DNA, have been attracted much attention in the field of nanomedicine [1]. On the other hand, mitochondrion has emerged as an important site-specific target for therapeutic and imaging purposes [2]. In our previous work, a mitochondria-targeting bionanoplatform has been constructed by using lipophilic cation triphenyl phosphonium (TPP) as a targeting molecule [3]. Nevertheless, how to improve the biocompatibility and biodegradability of the mitochondria-targeting bionanoplatform is still a challenge for the design and synthesis of drug delivery nanocarriers. Herein, a biodegradable protein-polymer bioconjugate ended with a TPP group (TPP-PDMA-b-P(DEGMA-co-NBDAE)-BSA) was synthesized, in which a hydrophobic pyridyl disulfide-functionalized copolymer was covalently linked to bovine serum albumin (BSA) through a pyridyl disulfide-sulfhydryl coupling method. The obtained amphiphilic TPP-modified bioconjugate could self-assemble into spherical micelles (Fig. 1). Confocal laser scanning microscopy (CLSM) analysis indicated that the micelles could be uptaken by HeLa cells and selectively localize in mitochondria. Furthermore, the TPP-modified bioconjugates loaded with doxorubicin showed a controlled release behavior, showing the potential applications in mitochondria-targeting drug delivery systems.
Yi Liua,b, Huiru Lub, Aiping Lanb, Yi Hub, Heping Lia,⁎, Jun Chenb,⁎ Key Laboratory of Road Structure and Material of Ministry of Transport, Hunan Provincial Key Laboratory of Materials Protection for Electric Power and Transportation, Changsha University of Science and Technology, Changsha 410114, China b CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, China ⁎Corresponding authors. E-mail addresses: [email protected] (Y. Liu), [email protected] (H. Li), [email protected] (J. Chen) a
Photodynamic therapy (PDT), as a noninvasive therapeutic procedure, has been successfully applied to treat tumors and other diseases. A new generation of photodynamic therapy that precisely functions against diseased cells and cellular organelles, is highly desired to circumvent those limitations in conventional photodynamic therapy (PDT). Herein, we develop a novel nanoplatform based on cationic amphiphilic polymer-wrapped carbon nanotubes (CNTs) and indocyanine green (ICG) for photodynamic therapy (PDT) has been successfully constructed (Fig. 1). The as-prepared nanoparticles exhibited excellent mitochondria targeting due to the synergistic property of highly positive charges on the surface and the highly hydrophobicity in the core [1, 2]. When irradiated upon 808 nm NIR laser in a very limited dose, the CNTs@ICG could precisely damage mitochondria by producing reactive oxygen species (ROS), which further induced the ROS burst release from nanoparticles-targeted mitochondria. The overproduced ROS accumulated in mitochondria ultimately resulted in mitochondrial collapse and irreversible cell apoptosis. In comparison with nontargeting nanoplatform, the enhanced HeLa cells lethality with less dose of the 808 nm laser is observed. Thus the CNTs@ICG can achieve an amplifying photodynamic therapeutic effect on cancer treatment.
Fig. 1. Schematic illustration of the self-assembly of protein-polymer conjugates for mitochondria-targeted drug delivery.
Keywords: self-assembly, BSA, biodegradable polymer, mitochondria targeting, drug delivery Acknowledgement This work was financed by the NSFC under Grant No. 51272002. References [1] M. Vendruscolo, C.M. Dobson, Structural biology: protein self-assembly intermediates. Nat. Chem. Biol. 9 (2013) 216-217. [2] S. Fulda, L. Galluzzi, G. Kroemer, Targeting mitochondria for cancer therapy. Nat. Rev. Drug Discov.9 (2010) 447-464. [3] Y. Zhang, Y.J. Shen, X.Y. Teng, M.Q. Yan, H. Bi, P.C. Morais, Mitochondria-Targeting nanoplatform with fluorescent carbon dots for long time imaging and magnetic fieldenhanced cellular uptake. ACS Appl. Mater. Interface 7 (2015) 10201-10212.
doi:10.1016/j.jconrel.2017.03.337
Fig. 1. Illustration of the preparation of CNTs@ICG nanocomposites and targeting mitochondria for amplifying photodynamic therapeutic effects.
Keywords: carbon nanotube, ICG, mitochondria, reactive oxygen species, photodynamic therapy Acknowledgements This work was supported by the National Natural Science Foundation of China (21304098, 21390411, 21574136), CAS Youth Innovation Promotion Association Program (2015008). References [1] F.F. Zhou, D. Xing, B.Y. Wu, S.N. Wu, Z.M. Ou, W.R. Chen, New insights of transmembranal mechanism and subcellular localization of noncovalently modified single-walled carbon nanotubes, Nano Lett. 10 (2010) 1677-1681.