Comb-like Poly(N-(2-hydroxypropyl) methacrylamide) Doxorubicin Conjugates: The Influence of Polymer Architecture and Composition on the Biological Properties

Hao Tang; Jin Tang; Yi Shen; Wen-Xuan Guo; Min Zhou; Rui-Hua Wang; Ni Jiang; Zhi-Hua Gan; Qing-Song Yu

doi:10.1007/s10118-018-2159-y

Your Location：

Home >

Browse articles >

Comb-like Poly(N-(2-hydroxypropyl) methacrylamide) Doxorubicin Conjugates: The Influence of Polymer Architecture and Composition on the Biological Properties

ARTICLE | Updated：2021-02-18

- Comb-like Poly(N-(2-hydroxypropyl) methacrylamide) Doxorubicin Conjugates: The Influence of Polymer Architecture and Composition on the Biological Properties
- Comb-like Poly(N-(2-hydroxypropyl) methacrylamide) Doxorubicin Conjugates: The Influence of Polymer Architecture and Composition on the Biological Properties
- Chinese Journal of Polymer Science 2018年36卷第11期页码：1225-1238
- Affiliations：
  
  a.The State Key Laboratory of Organic-inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China
  b.College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
  c.Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China
- Author bio：
  
  zhgan@mail.buct.edu.cn (Z.H.G.)
  yuqs@mail.buct.edu.cn (Q.S.Y.)
- Funds：
  
  This work was financially supported by the National Natural Science Foundation of China (Nos. 51503013, 51390481, 21774008 and 81472412). This work was also supported by the Fundamental Research Funds for the Central Universities (Nos. ZY1519 and XK1701) and by the long-term subsidy mechanism from the Ministry of Finance and the Ministry of Education of PRC for BUCT.
- DOI：10.1007/s10118-018-2159-y
  中图分类号：
- 收稿：2018-04-18，
  
  修回：2018-5-14，
  
  录用：2018-5-15，
  
  网络首发：2018-06-30，
  
  纸质出版：2018-11
- Accepted：
Scan QR Code
Citation: Tang, H.; Tang, J.; Shen, Y.; Guo, W. X.; Zhou, M.; Wang, R. H.; Jiang, N.; Gan, Z. H.; Yu, Q. S. Comb-like Poly( N-(2-hydroxypropyl) methacrylamide) Doxorubicin Conjugates: The Influence of Polymer Architecture and Composition on the Biological Properties. Chinese J. Polym. Sci. 2018, 36(11), 1225–1238.

Hao Tang, Jin Tang, Yi Shen, et al. Comb-like Poly(N-(2-hydroxypropyl) methacrylamide) Doxorubicin Conjugates: The Influence of Polymer Architecture and Composition on the Biological Properties[J]. Chinese Journal of Polymer Science, 2018, 36(11): 1225-1238.
Citation: Tang, H.; Tang, J.; Shen, Y.; Guo, W. X.; Zhou, M.; Wang, R. H.; Jiang, N.; Gan, Z. H.; Yu, Q. S. Comb-like Poly( N-(2-hydroxypropyl) methacrylamide) Doxorubicin Conjugates: The Influence of Polymer Architecture and Composition on the Biological Properties. Chinese J. Polym. Sci. 2018, 36(11), 1225–1238. DOI： 10.1007/s10118-018-2159-y.

Hao Tang, Jin Tang, Yi Shen, et al. Comb-like Poly(N-(2-hydroxypropyl) methacrylamide) Doxorubicin Conjugates: The Influence of Polymer Architecture and Composition on the Biological Properties[J]. Chinese Journal of Polymer Science, 2018, 36(11): 1225-1238. DOI： 10.1007/s10118-018-2159-y.

摘要

Abstract

The synthesis and structure-property correlation of poly(

-(2-hydroxypropyl) methacrylamide) (PHPMA) conjugates with various architectures including random

block

branched or star-like structures and compositions have been thoroughly explored. However

related synthesis and structure-property data are still lacking for comb-like PHPMA. In this work

we report the synthesis of comb-like PHPMA copolymer-doxorubicin (DOX) conjugates with different backbone/side-chain lengths and location of drug moieties. Well-defined comb-like PHPMA-DOX conjugates are obtained

via

the combination of controlled radical polymerization and fractional precipitation techniques. The influences of structural factors on the biological properties such as cellular uptake

blood circulation and tumor accumulation have been investigated. Long blood circulation and efficient tumor accumulation can be achieved by proper control of the comb number

length and location of drug moieties. These facile comb-like structures possess great potentials in future theranostics for brachytherapy or surgical navigation.

关键词

Keywords

references

Liu, D.; Poon, C.; Lu, K.; He, C.; Lin, W . Self-assembled nanoscale coordination polymers with trigger release properties for effective anticancer therapy . Nat. Commun. , 2014 . 5 4182 DOI: 10.1038/ncomms5182 http://doi.org/10.1038/ncomms5182 .

Maeda, H.; Nakamura, H.; Fang, J . The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo . Adv. Drug Deliver. Rev. , 2013 . 65 ( 1 ): 71 - 79 . DOI: 10.1016/j.addr.2012.10.002 http://doi.org/10.1016/j.addr.2012.10.002 .

Iyer, A. K.; Khaled, G.; Fang, J.; Maeda, H . Exploiting the enhanced permeability and retention effect for tumor targeting . Drug Discover. Today , 2006 . 11 ( 17 ): 812 - 818 . .

Liu, D, H., Ding, J. X., Xu W. G., Song, X. F., Zhuang, X. L, Chen X. S . Stereocomplex micelles based on 4-armed poly(ethylene glycol)-polylactide enantiomeric copolymers for drug delivery . Acta Polymerica Sinica (in Chinese) , 2014 . ( 9 ): 1265 - 1273 . .

Blanco, E.; Shen, H.; Ferrari, M . Principles of nanoparticle design for overcoming biological barriers to drug delivery . Nat. Biotechnol. , 2015 . 33 ( 9 ): 941 - 951 . DOI: 10.1038/nbt.3330 http://doi.org/10.1038/nbt.3330 .

Haag, R.; Kratz, F . Polymer therapeutics: Concepts and applications . Angew. Chem. Int. Ed. , 2006 . 45 ( 8 ): 1198 - 1215 . DOI: 10.1002/(ISSN)1521-3773 http://doi.org/10.1002/(ISSN)1521-3773 .

Pasut, G.; Veronese, F. M . PEG conjugates in clinical development or use as anticancer agents: An overview . Adv. Drug Deliver. Rev. , 2009 . 61 ( 13 ): 1177 - 1188 . DOI: 10.1016/j.addr.2009.02.010 http://doi.org/10.1016/j.addr.2009.02.010 .

Fox, M. E.; Szoka, F. C.; Fréchet, J. M . Soluble polymer carriers for the treatment of cancer: the importance of molecular architecture . Acc. Chem. Res. , 2009 . 42 ( 8 ): 1141 - 1151 . DOI: 10.1021/ar900035f http://doi.org/10.1021/ar900035f .

Qiu, L. Y.; Bae, Y. H . Polymer architecture and drug delivery . Pharm. Res. , 2006 . 23 ( 1 ): 1 - 30 . DOI: 10.1007/s11095-005-9046-2 http://doi.org/10.1007/s11095-005-9046-2 .

Murakami, Y.; Tabata, Y.; Ikada, Y . Tumor accumulation of poly (ethylene glycol) with different molecular weights after intravenous injection . Drug Deliver. , 1997 . 4 ( 1 ): 23 - 31 . DOI: 10.3109/10717549709033184 http://doi.org/10.3109/10717549709033184 .

Tabata, Y.; Murakami, Y.; Ikada, Y . Tumor accumulation of poly (vinyl alcohol) of different sizes after intravenous injection . J. Control. Release , 1998 . 50 ( 1-3 ): 123 - 133 . DOI: 10.1016/S0168-3659(97)00129-6 http://doi.org/10.1016/S0168-3659(97)00129-6 .

Lim, J.; Guo, Y.; Rostollan, C. L.; Stanfield, J.; Hsieh, J. T.; Sun, X.; Simanek, E. E . The role of the size and number of polyethylene glycol chains in the biodistribution and tumor localization of triazine dendrimers . Mol. Pharmaceutics , 2008 . 5 ( 4 ): 540 - 547 . DOI: 10.1021/mp8000292 http://doi.org/10.1021/mp8000292 .

Venturoli, D.; Rippe, B . Ficoll and dextran versus globular proteins as probes for testing glomerular permselectivity: effects of molecular size, shape, charge, and deformability . Am. J. Physiol. Renal Physiol. , 2005 . 288 ( 4 ): F605 - F613 . DOI: 10.1152/ajprenal.00171.2004 http://doi.org/10.1152/ajprenal.00171.2004 .

Asgeirsson, D.; Venturoli, D.; Fries, E.; Rippe, B.; Rippe, C . Glomerular sieving of three neutral polysaccharides, polyethylene oxide and bikunin in rat . Effects of molecular size and conformation. Acta Physiol. , 2007 . 191 ( 3 ): 237 - 246 . .

Gillies, E. R.; Dy, E.; Fréchet, J. M.; Szoka, F. C . Biological evaluation of polyester dendrimer: poly(ethylene oxide) " bow-tie” hybrids with tunable molecular weight and architecture . Mol. Pharmaceutics , 2005 . 2 ( 2 ): 129 - 138 . DOI: 10.1021/mp049886u http://doi.org/10.1021/mp049886u .

Lee, C. C.; Gillies, E. R.; Fox, M. E.; Guillaudeu, S. J.; Fréchet, J. M.; Dy, E. E.; Szoka, F. C . A single dose of doxorubicin-functionalized bow-tie dendrimer cures mice bearing C-26 colon carcinomas . Proc. Natl. Acad. Sci. U. S. A. , 2006 . 103 ( 45 ): 16649 - 16654 . DOI: 10.1073/pnas.0607705103 http://doi.org/10.1073/pnas.0607705103 .

Li, Y.; Xu, X.; Zhang, X.; Li, Y.; Zhang, Z.; Gu, Z . Tumor-specific multiple stimuli-activated dendrimeric nanoassemblies with metabolic blockade surmount chemotherapy resistance . ACS Nano , 2017 . 11 ( 1 ): 416 - 429 . DOI: 10.1021/acsnano.6b06161 http://doi.org/10.1021/acsnano.6b06161 .

Liu, C.; Chen, Y. X.; Wang, J. F.; Luo, X.; Huang, Y. D.; Xu, J. L.; Yan, G. P.; Chen, S.; Zhang, X, Z . A multi-functional drug delivery system based on dendritic peptide for tumor nuclear accurate targeting therapy . Acta Polymerica Sinica (in Chinese) , 2048 . ( 6 ): 682 - 691 . DOI: 10.11777/j.issn1000-3304.2017.17335 http://doi.org/10.11777/j.issn1000-3304.2017.17335 .

Lee, C. C.; MacKay, J. A.; Frechet, J. M. J.; Szoka, F. C . Designing dendrimers for biological applications . Nat. Biotechnol. , 2005 . 23 ( 12 ): 1517 - 1526 . DOI: 10.1038/nbt1171 http://doi.org/10.1038/nbt1171 .

Allmeroth, M.; Moderegger, D.; Gündel, D.; Buchholz, H. G.; Mohr, N.; Koynov, K.; Rösch, F.; Thews, O.; Zentel, R . PEGylation of HPMA-based block copolymers enhances tumor accumulation in vivo : A quantitative study using radiolabeling and positron emission tomography . J. Control. Release , 2013 . 172 ( 1 ): 77 - 85 . DOI: 10.1016/j.jconrel.2013.07.027 http://doi.org/10.1016/j.jconrel.2013.07.027 .

Allmeroth, M.; Moderegger, D.; Gündel, D.; Koynov, K.; Buchholz, H. G.; Mohr, K.; Rösch, F.; Zentel, R.; Thews, O . HPMA-LMA copolymer drug carriers in oncology: an in vivo PET study to assess the tumor line-specific polymer uptake and body distribution . Biomacromolecules , 2013 . 14 ( 9 ): 3091 - 3101 . DOI: 10.1021/bm400709z http://doi.org/10.1021/bm400709z .

Müllner, M.; Dodds, S. J.; Nguyen, T. H.; Senyschyn, D.; Porter, C. J.; Boyd, B. J.; Caruso, F . Size and rigidity of cylindrical polymer brushes dictate long circulating properties in vivo . ACS Nano , 2015 . 9 ( 2 ): 1294 - 1304 . DOI: 10.1021/nn505125f http://doi.org/10.1021/nn505125f .

Irvine, D.; Mayes, A.; Griffith-Cima, L . Self-consistent field analysis of grafted star polymers . Macromolecules , 1996 . 29 ( 18 ): 6037 - 6043 . DOI: 10.1021/ma951903t http://doi.org/10.1021/ma951903t .

Li, X.; Ji, J.; Wang, X.; Wang, Y.; Shen, J . Stability and drug loading of spontaneous vesicles of comb‐like PEG derivates . Macromol. Rapid Commun. , 2007 . 28 ( 5 ): 660 - 665 . DOI: 10.1002/(ISSN)1521-3927 http://doi.org/10.1002/(ISSN)1521-3927 .

Chen, C. J.; Liu, G. Y.; Shi, Y. T.; Zhu, C. S.; Pang, S. P.; Liu, X. S.; Ji, J . Biocompatible micelles based on comb‐like PEG derivates: formation, characterization, and photo‐responsiveness . Macromol. Rapid Commun. , 2011 . 32 ( 14 ): 1077 - 1081 . DOI: 10.1002/marc.v32.14 http://doi.org/10.1002/marc.v32.14 .

Talelli, M.; Rijcken, C.; van Nostrum, C.; Storm, G.; Hennink, W . Micelles based on HPMA copolymers . Adv. Drug Deliver. Rev. , 2010 . 62 ( 2 ): 231 - 239 . DOI: 10.1016/j.addr.2009.11.029 http://doi.org/10.1016/j.addr.2009.11.029 .

Kopeček, J.; Kopečková, P . HPMA copolymers: origins, early developments, present, and future . Adv. Drug Deliver. Rev. , 2010 . 62 ( 2 ): 122 - 149 . DOI: 10.1016/j.addr.2009.10.004 http://doi.org/10.1016/j.addr.2009.10.004 .

Kopeček, J.; Kopečková, P.; Minko, T.; Lu, Z. R . HPMA copolymer–anticancer drug conjugates: design, activity, and mechanism of action . Eur. J. Pharm. Biopharm. , 2000 . 50 ( 1 ): 61 - 81 . DOI: 10.1016/S0939-6411(00)00075-8 http://doi.org/10.1016/S0939-6411(00)00075-8 .

Šírová, M.; Strohalm, J.; Chytil, P.; Lidický, O.; Tomala, J.; Říhová, B.; Etrych, T . The structure of polymer carriers controls the efficacy of the experimental combination treatment of tumors with HPMA copolymer conjugates carrying doxorubicin and docetaxel . J. Control. Release , 2017 . 246 1 - 11 . DOI: 10.1016/j.jconrel.2016.12.004 http://doi.org/10.1016/j.jconrel.2016.12.004 .

Etrych, T.; Kovar, L.; Strohalm, J.; Chytil, P.; Rihova, B.; Ulbrich, K . Biodegradable star HPMA polymer-drug conjugates: Biodegradability, distribution and anti-tumor efficacy . J. Control. Release , 2011 . 154 ( 3 ): 241 - 248 . DOI: 10.1016/j.jconrel.2011.06.015 http://doi.org/10.1016/j.jconrel.2011.06.015 .

Tomalova, B.; Sirova, M.; Rossmann, P.; Pola, R.; Strohalm, J.; Chytil, P.; Cerny, V.; Tomala, J.; Kabesova, M.; Rihova, B.; Ulbrich, K.; Etrych, T.; Kovar, M . The structure-dependent toxicity, pharmacokinetics and anti-tumour activity of HPMA copolymer conjugates in the treatment of solid tumours and leukaemia . J. Control. Release , 2016 . 223 1 - 10 . DOI: 10.1016/j.jconrel.2015.12.023 http://doi.org/10.1016/j.jconrel.2015.12.023 .

Etrych, T.; Chytil, P.; Mrkvan, T.; Šírová, M.; Říhová, B.; Ulbrich, K . Conjugates of doxorubicin with graft HPMA copolymers for passive tumor targeting . J. Control. Release , 2008 . 132 ( 3 ): 184 - 192 . DOI: 10.1016/j.jconrel.2008.04.017 http://doi.org/10.1016/j.jconrel.2008.04.017 .

Wang, D . Synthesis of starlike N -(2-hydroxypropyl)-methacrylamide copolymers: Potential drug carriers . Biomacromolecules , 2000 . 1 ( 3 ): 313 - 319 . DOI: 10.1021/bm0000236 http://doi.org/10.1021/bm0000236 .

Etrych, T.; Subr, V.; Strohalm, J.; Sirova, M.; Rihova, B.; Ulbrich, K . HPMA copolymer-doxorubicin conjugates: The effects of molecular weight and architecture on biodistribution and in vivo activity . J. Control. Release , 2012 . 164 ( 3 ): 346 - 354 . DOI: 10.1016/j.jconrel.2012.06.029 http://doi.org/10.1016/j.jconrel.2012.06.029 .

Fox, M. E.; Szoka, F. C.; Frechet, J. M. J . Soluble polymer carriers for the treatment of cancer: the importance of molecular architecture . Acc. Chem. Res. , 2009 . 42 ( 8 ): 1141 - 1151 . DOI: 10.1021/ar900035f http://doi.org/10.1021/ar900035f .

Yu, Q.; Zhang, J.; Zhang, G.; Gan, Z . Synthesis and functions of well‐defined polymer‐drug conjugates as efficient nanocarriers for intravesical chemotherapy of bladder cancer . Macromol. Biosci. , 2015 . 15 ( 4 ): 509 - 520 . DOI: 10.1002/mabi.v15.4 http://doi.org/10.1002/mabi.v15.4 .

Mitsukami, Y.; Donovan, M. S.; Lowe, A. B.; McCormick, C. L . Water-soluble polymers . 81. Direct synthesis of hydrophilic styrenic-based homopolymers and block copolymers in aqueous solution via RAFT. Macromolecules , 2001 . 34 ( 7 ): 2248 - 2256 . .

Stals, P. J. M.; Li, Y.; Burdyńska, J.; Nicolaÿ, R.; Nese, A.; Palmans, A. R. A.; Meijer, E. W.; Matyjaszewski, K.; Sheiko, S. S . How far can we push polymer architectures? . J. Am. Chem. Soc. , 2013 . 135 ( 31 ): 11421 - 11424 . DOI: 10.1021/ja400890v http://doi.org/10.1021/ja400890v .

Shen, T.; Xu, X.; Guo, L.; Tang, H.; Diao, T.; Gan, Z.; Zhang, G.; Yu, Q . Efficient tumor accumulation, penetration and tumor growth inhibition achieved by polymer therapeutics: The effect of polymer architectures . Biomacromolecules , 2017 . 18 ( 1 ): 217 - 230 . DOI: 10.1021/acs.biomac.6b01533 http://doi.org/10.1021/acs.biomac.6b01533 .

Seymour, L. W.; Ulbrich, K.; Strohalm, J.; Kopecek, J.; Duncan, R . The pharmacokinetics of polymer-bound adriamycin . Biochem. Pharmacol. , 1990 . 39 ( 6 ): 1125 - 1131 . DOI: 10.1016/0006-2952(90)90293-T http://doi.org/10.1016/0006-2952(90)90293-T .

Hedden, R. C.; Bauer, B. J.; Smith, A. P.; Grohn, F.; Amis, E . Templating of inorganic nanoparticles by PAMAM/PEG dendrimer-star polymers . Polymer , 2002 . 43 ( 20 ): 5473 - 5481 . DOI: 10.1016/S0032-3861(02)00428-7 http://doi.org/10.1016/S0032-3861(02)00428-7 .

Hedden, R. C.; Bauer, B. J . Structure and dimensions of PAMAM/PEG dendrimer-star polymers . Macromolecules , 2003 . 36 ( 6 ): 1829 - 1835 . DOI: 10.1021/ma025752n http://doi.org/10.1021/ma025752n .

Chen, C. J.; Liu, G. Y.; Shi, Y. T.; Zhu, C. S.; Pang, S. P.; Liu, X. S.; Ji, J . Biocompatible micelles based on comb-like PEG derivates: Formation, characterization, and photo-responsiveness . Macromol. Rapid Commun. , 2011 . 32 ( 14 ): 1077 - 1081 . DOI: 10.1002/marc.v32.14 http://doi.org/10.1002/marc.v32.14 .

Bo, G.; Wesslén, B.; Wessléen, K. B . Amphiphilic comb-shaped polymers from poly(ethylene glycol) macromonomers . J. Polym. Sci., Part A: Polym. Chem. , 1992 . 30 ( 9 ): 1799 - 1808 . DOI: 10.1002/pola.1992.080300903 http://doi.org/10.1002/pola.1992.080300903 .

Matyjaszewski, K.; Tsarevsky, N. V . Nanostructured functional materials prepared by atom transfer radical polymerization . Nat. Chem. , 2009 . 1 ( 4 ): 276 - 288 . DOI: 10.1038/nchem.257 http://doi.org/10.1038/nchem.257 .

Sheiko, S. S.; Sumerlin, B. S.; Matyjaszewski, K . Cylindrical molecular brushes: Synthesis, characterization, and properties . Prog. Polym. Sci. , 2008 . 33 ( 7 ): 759 - 785 . DOI: 10.1016/j.progpolymsci.2008.05.001 http://doi.org/10.1016/j.progpolymsci.2008.05.001 .

Plamper, F. A.; Schmalz, A.; Penott-Chang, E.; Drechsler, M.; Jusufi, A.; Ballauff, M.; Müller, A. H. E . Influence of molecular weight on passive tumour accumulation of a soluble macromolecular drug carrier . Eur. J. Cancer , 1995 . 31A ( 5 ): 766 - 770 . .

Seymour, L. W.; Miyamoto, Y.; Maeda, H.; Brereton, M.; Strohalm, J.; Ulbrich, K.; Duncan, R . Influence of molecular weight on passive tumour accumulation of a soluble macromolecular drug carrier . Eur. J. Cancer , 1995 . 31 ( 5 ): 766 - 770 . DOI: 10.1016/0959-8049(94)00514-6 http://doi.org/10.1016/0959-8049(94)00514-6 .

Yu, Q.; Wei, Z.; Shi, J.; Guan, S.; Du, N.; Shen, T.; Tang, H.; Jia, B.; Wang, F.; Gan, Z . Polymer–doxorubicin conjugate micelles based on poly (ethylene glycol) and poly ( N -(2-hydroxypropyl) methacrylamide): Effect of negative charge and molecular weight on biodistribution and blood clearance . Biomacromolecules , 2015 . 16 ( 9 ): 2645 - 2655 . DOI: 10.1021/acs.biomac.5b00460 http://doi.org/10.1021/acs.biomac.5b00460 .

Neugebauer, D.; Sumerlin, B. S.; Matyjaszewski, K.; Goodhart, B.; Sheiko, S. S . How dense are cylindrical brushes grafted from a multifunctional macroinitiator? . Polymer , 2004 . 45 ( 24 ): 8173 - 8179 . DOI: 10.1016/j.polymer.2004.09.069 http://doi.org/10.1016/j.polymer.2004.09.069 .

Hu, Y.; Xie, J.; Tong, Y. W.; Wang, C. H . Effect of PEG conformation and particle size on the cellular uptake efficiency of nanoparticles with the HepG2 cells . J. Control. Release , 2007 . 118 ( 1 ): 7 - 17 . DOI: 10.1016/j.jconrel.2006.11.028 http://doi.org/10.1016/j.jconrel.2006.11.028 .

Zhang, S.; Li, J.; Lykotrafitis, G.; Bao, G.; Suresh, S . Size‐dependent endocytosis of nanoparticles . Adv. Mater. , 2009 . 21 ( 4 ): 419 - 424 . DOI: 10.1002/adma.v21:4 http://doi.org/10.1002/adma.v21:4 .

Gref, R.; Lück, M.; Quellec, P.; Marchand, M.; Dellacherie, E.; Harnisch, S.; Blunk, T.; Müller, R. H . ‘Stealth’ corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption . Colloids Surf., B , 2000 . 18 ( 3 ): 301 - 313 . .

Liu, J.; Bauer, H.; Callahan, J.; Kopečková, P.; Pan, H.; Kopeček, J . Endocytic uptake of a large array of HPMA copolymers: Elucidation into the dependence on the physicochemical characteristics . J. Control. Release , 2010 . 143 ( 1 ): 71 - 79 . DOI: 10.1016/j.jconrel.2009.12.022 http://doi.org/10.1016/j.jconrel.2009.12.022 .

Swift, L. P.; Rephaeli, A.; Nudelman, A.; Phillips, D. R.; Cutts, S. M . Doxorubicin-DNA adducts induce a non-topoisomerase II-mediated form of cell death . Cancer Res. , 2006 . 66 ( 9 ): 4863 - 4871 . DOI: 10.1158/0008-5472.CAN-05-3410 http://doi.org/10.1158/0008-5472.CAN-05-3410 .

Lin, W.; Zhang, X.; Qian, L.; Yao, N.; Pan, Y.; Zhang, L . Doxorubicin-loaded unimolecular micelle-stabilized gold nanoparticles as a theranostic nanoplatform for tumor-targeted chemotherapy and computed tomography imaging . Biomacromolecules , 2017 . 18 ( 12 ): 3869 - 3880 . DOI: 10.1021/acs.biomac.7b00810 http://doi.org/10.1021/acs.biomac.7b00810 .

Gratton, S. E.; Ropp, P. A.; Pohlhaus, P. D.; Luft, J. C.; Madden, V. J.; Napier, M. E.; DeSimone, J. M . The effect of particle design on cellular internalization pathways . Proc. Natl. Acad. Sci. U. S. A. , 2008 . 105 ( 33 ): 11613 - 11618 . DOI: 10.1073/pnas.0801763105 http://doi.org/10.1073/pnas.0801763105 .

Meng, H.; Yang, S.; Li, Z. X.; Xia, T.; Chen, J.; Ji, Z. X.; Zhang, H. Y.; Wang, X.; Lin, S. J.; Huang, C.; Zhou, Z. H.; Zink, J. I.; Nel, A. E . Aspect ratio determines the quantity of mesoporous silica nanoparticle uptake by a small GTPase-dependent macropinocytosis mechanism . ACS Nano , 2011 . 5 ( 6 ): 4434 - 4447 . DOI: 10.1021/nn103344k http://doi.org/10.1021/nn103344k .

Hu, X.; Hu, J.; Tian, J.; Ge, Z.; Zhang, G.; Luo, K.; Liu, S . Polyprodrug amphiphiles: hierarchical assemblies for shape-regulated cellular internalization, trafficking, and drug delivery . J. Am. Chem. Soc. , 2013 . 135 ( 46 ): 17617 - 17629 . DOI: 10.1021/ja409686x http://doi.org/10.1021/ja409686x .

Hu, X.; Liu, G.; Li, Y.; Wang, X.; Liu, S . Cell-penetrating hyperbranched polyprodrug amphiphiles for synergistic reductive milieu-triggered drug release and enhanced magnetic resonance signals . J. Am. Chem. Soc. , 2015 . 137 ( 1 ): 362 - 368 . DOI: 10.1021/ja5105848 http://doi.org/10.1021/ja5105848 .

French, A. P.; Mills, S.; Swarup, R.; Bennett, M. J.; Pridmore, T. P . Colocalization of fluorescent markers in confocal microscope images of plant cells . Nat. Protoc. , 2008 . 3 ( 4 ): 619 - 628 . DOI: 10.1038/nprot.2008.31 http://doi.org/10.1038/nprot.2008.31 .

Bolte, S.; Cordelieres, F . A guided tour into subcellular colocalization analysis in light microscopy . J. Microsc. , 2006 . 224 ( 3 ): 213 - 232 . DOI: 10.1111/jmi.2006.224.issue-3 http://doi.org/10.1111/jmi.2006.224.issue-3 .

Adler, J.; Parmryd, I . Quantifying colocalization by correlation: the Pearson correlation coefficient is superior to the Mander's overlap coefficient . Cytometry Part A , 2010 . 77 ( 8 ): 733 - 742 . .

Mullner, M.; Dodds, S. J.; Nguyen, T. H.; Senyschyn, D.; Porter, C. J. H.; Boyd, B. J.; Caruso, F . Size and rigidity of cylindrical polymer brushes dictate long circulating properties in vivo . ACS Nano , 2015 . 9 ( 2 ): 1294 - 1304 . DOI: 10.1021/nn505125f http://doi.org/10.1021/nn505125f .

浏览量

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

工具集

关联资源

Understand the Temperature Sensing Behavior of Solid-state Polymerized PEDOT Hybrid Based on X-ray Scattering Studies

Conformation of an Amphiphilic Comb-like Copolymer in a Selective Solvent

Preparation of Poly(phosphoric acid piperazine) and Its Application as an Effective Flame Retardant for Epoxy Resin

Pyrimidoisoindigo-based Polymers for Ambipolar Charge Transport

Durable Anti-fogging and Abrasion-resistant Coatings Based on Polyoxometalates-Hydrophilic Resin Composites with Enhanced Cohesion and Adhesion