A Copper-Mediated Disulfiram-Loaded pH-Triggered PEG-Shedding TAT Peptide-Modified Lipid Nanocapsules for Use in Tumor Therapy

ACS Applied Materials and Interfaces

Volumn 7, Issue 45, 2015, Pages 25147-25161

  Zhang, Ling ^a   Tian, Bin ^a   Li, Yi ^a   Lei, Tian ^a   Meng, Jia ^a   Yang, Liu ^a   Zhang, Yan ^b   Chen, Fen ^a,c   Zhang, Haotian ^a   Xu, Hui ^a   Zhang, Yu ^a   Tang, Xing ^a  

^a SHENYANG PHARMACEUTICAL UNIVERSITY   (China)

^b SHENYANG UNIVERSITY   (China)

^c LIAONING UNIVERSITY OF TRADITIONAL CHINESE MEDICINE   (China)

Author keywords

copper; disulfiram; lipid nanocapsules; pH sensitive; sheddable; TAT peptide

Indexed keywords

CHAINS; COPPER; NANOCAPSULES; PEPTIDES; PH SENSORS; PHARMACOKINETICS; POLYETHYLENE OXIDES; TUMORS;

DISULFIRAM; LIPID NANOCAPSULES; PH SENSITIVE; SHEDDABLE; TAT PEPTIDE;

POLYETHYLENE GLYCOLS;

COPPER; DISULFIRAM; LIPID; MACROGOL DERIVATIVE; NANOCAPSULE; POLYSORBATE; TRANSACTIVATOR PROTEIN;

ANIMAL; APOPTOSIS; BAGG ALBINO MOUSE; CELL SURVIVAL; CHEMISTRY; DRUG EFFECTS; DRUG RELEASE; ENDOCYTOSIS; HEPG2 CELL LINE; HUMAN; IC50; MASS SPECTROMETRY; NEAR INFRARED SPECTROSCOPY; NEOPLASMS; NUDE MOUSE; PARTICLE SIZE; PH; PROTON NUCLEAR MAGNETIC RESONANCE; STATIC ELECTRICITY; SYNTHESIS; TISSUE DISTRIBUTION;

ANIMALS; APOPTOSIS; CELL SURVIVAL; COPPER; DISULFIRAM; DRUG LIBERATION; ENDOCYTOSIS; HEP G2 CELLS; HUMANS; HYDROGEN-ION CONCENTRATION; INHIBITORY CONCENTRATION 50; LIPIDS; MASS SPECTROMETRY; MICE, INBRED BALB C; MICE, NUDE; NANOCAPSULES; NEOPLASMS; PARTICLE SIZE; POLYETHYLENE GLYCOLS; POLYSORBATES; PROTON MAGNETIC RESONANCE SPECTROSCOPY; SPECTROSCOPY, NEAR-INFRARED; STATIC ELECTRICITY; TAT GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; TISSUE DISTRIBUTION;

EID: 84947704114     PISSN: 19448244     EISSN: 19448252     Source Type: Journal    
DOI: 10.1021/acsami.5b06488     Document Type: Article

References (60)

1. Wickstrom, M.; Danielsson, K.; Rickardson, L.; Gullbo, J.; Nygren, P.; Isaksson, A.; Larsson, R.; Lovborg, H. Pharmacological Profiling of Disulfiram Using Human Tumor Cell Lines and Human Tumor Cells from Patients Biochem. Pharmacol. 2007, 73 (1) 25-33 10.1016/j.bcp.2006.08.016
2. Conticello, C.; Martinetti, D.; Adamo, L.; Buccheri, S.; Giuffrida, R.; Parrinello, N.; Lombardo, L.; Anastasi, G.; Amato, G.; Cavalli, M.; Chiarenza, A.; De Maria, R.; Giustolisi, R.; Gulisano, M.; Di Raimondo, F. Disulfiram, an Old Drug with New Potential Therapeutic Uses for Human Hematological Malignancies Int. J. Cancer 2012, 131 (9) 2197-2203 10.1002/ijc.27482
3. Triscott, J.; Rose Pambid, M.; Dunn, S. E. Concise Review: Bullseye: Targeting Cancer Stem Cells to Improve the Treatment of Gliomas by Repurposing Disulfiram Stem Cells 2015, 33 (4) 1042-1046 10.1002/stem.1956
4. Wang, F.; Zhai, S.; Liu, X.; Li, L.; Wu, S.; Dou, Q. P.; Yan, B. A Novel Dithiocarbamate Analogue with Potentially Decreased ALDH Inhibition Has Copper-dependent Proteasome-inhibitory and Apoptosis-inducing Activity in Human Breast Cancer Cells Cancer Lett. 2011, 300 (1) 87-95 10.1016/j.canlet.2010.09.010
5. Shian, S. G.; Kao, Y. R.; Wu, F. Y.; Wu, C. W. Inhibition of Invasion and Angiogenesis by Zinc-chelating Agent Disulfiram Mol. Pharmacol. 2003, 64 (5) 1076-1084 10.1124/mol.64.5.1076
6. Cheriyan, V. T.; Wang, Y.; Muthu, M.; Jamal, S.; Chen, D.; Yang, H.; Polin, L. A.; Tarca, A. L.; Pass, H. I.; Dou, Q. P.; Sharma, S.; Wali, A.; Rishi, A. K. Disulfiram Suppresses Growth of the Malignant Pleural Mesothelioma Cells in Part by Inducing Apoptosis PLoS One 2014, 9 (4) e93711 10.1371/journal.pone.0093711
7. Hothi, P.; Martins, T. J.; Chen, L.; Deleyrolle, L.; Yoon, J. G.; Reynolds, B.; Foltz, G. High-throughput Chemical Screens Identify Disulfiram as an Inhibitor of Human Glioblastoma Stem Cells Oncotarget 2012, 3 (10) 1124-1136 10.18632/oncotarget.707
8. Duan, X.; Xiao, J.; Yin, Q.; Zhang, Z.; Yu, H.; Mao, S.; Li, Y. Multi-targeted Inhibition of Tumor Growth and Lung Metastasis by Redox-sensitive Shell Crosslinked Micelles Loading Disulfiram Nanotechnology 2014, 25 (12) 125102 10.1088/0957-4484/25/12/125102
9. Navrátilová, J.; Jungová, P.; Vanhara, P.; Preisler, J.; Smarda, J. Copper Ions Regulate Cytotoxicity of Disulfiram to Myeloid Leukemia Cells Int. J. Mol. Med. 2009, 24 (05) 661-670 10.3892/ijmm-00000277
10. Allensworth, J. L.; Evans, M. K.; Bertucci, F.; Aldrich, A. J.; Festa, R. A.; Finetti, P.; Ueno, N. T.; Safi, R.; McDonnell, D. P.; Thiele, D. J.; Van Laere, S.; Devi, G. R. Disulfiram (DSF) Acts as a Copper Ionophore to Induce Copper-dependent Oxidative Stress and Mediate Anti-tumor Efficacy in Inflammatory Breast Cancer Mol. Oncol. 2015, 9 (6) 1155-1168 10.1016/j.molonc.2015.02.007
11. Gupte, A.; Mumper, R. J. Elevated Copper and Oxidative Stress in Cancer Cells as a Target for Cancer Treatment Cancer Treat. Rev. 2009, 35 (1) 32-46 10.1016/j.ctrv.2008.07.004
12. Tisato, F.; Marzano, C.; Porchia, M.; Pellei, M.; Santini, C. Copper in Diseases and Treatments, and Copper-based Anticancer Strategies Med. Res. Rev. 2009, 30 (4) 708-749 10.1002/med.20174
13. Xu, B.; Shi, P.; Fombon, I. S.; Zhang, Y.; Huang, F.; Wang, W.; Zhou, S. Disulfiram/copper Complex Activated JNK/c-jun Pathway and Sensitized Cytotoxicity of Doxorubicin in Doxorubicin Resistant Leukemia HL60 Cells Blood Cells, Mol., Dis. 2011, 47 (4) 264-269 10.1016/j.bcmd.2011.08.004
14. Chen, D.; Cui, Q. C.; Yang, H.; Dou, Q. P. Disulfiram, a Clinically Used Anti-alcoholism Drug and Copper-binding Agent, Induces Apoptotic Cell Death in Breast Cancer Cultures and Xenografts via Inhibition of the Proteasome Activity Cancer Res. 2006, 66 (21) 10425-10433 10.1158/0008-5472.CAN-06-2126
15. Li, L.; Yang, H.; Chen, D.; Cui, C.; Ping Dou, Q. Disulfiram Promotes the Conversion of Carcinogenic Cadmium to a Proteasome Inhibitor with Pro-apoptotic Activity in Human Cancer Cells Toxicol. Appl. Pharmacol. 2008, 229 (2) 206-214 10.1016/j.taap.2008.01.022
16. Liu, P.; Brown, S.; Goktug, T.; Channathodiyil, P.; Kannappan, V.; Hugnot, J. P.; Guichet, P. O.; Bian, X.; Armesilla, A. L.; Darling, J. L.; Wang, W. Cytotoxic Effect of Disulfiram/copper on Human Glioblastoma Cell Lines and ALDH-positive Cancer-stem-like Cells Br. J. Cancer 2012, 107 (9) 1488-1497 10.1038/bjc.2012.442
17. Yip, N. C.; Fombon, I. S.; Liu, P.; Brown, S.; Kannappan, V.; Armesilla, A. L.; Xu, B.; Cassidy, J.; Darling, J. L.; Wang, W. Disulfiram Modulated ROS-MAPK and NF-κB Pathways and Targeted Breast Cancer Cells With Cancer Stem Cell-like Properties Br. J. Cancer 2011, 104 (10) 1564-1574 10.1038/bjc.2011.126
18. Fruehauf, J. P.; Trapp, V. Reactive oxygen species an Achilles' heel of melanoma Expert Rev. Anticancer Ther. 2008, 8 (11) 1751-1757 10.1586/14737140.8.11.1751
19. Zha, J.; Chen, F.; Dong, H.; Shi, P.; Yao, Y.; Zhang, Y.; Li, R.; Wang, S.; Li, P.; Wang, W.; Xu, B. Disulfiram Targeting Lymphoid Malignant Cell Lines via ROS-JNK Activation as well as Nrf2 and NF-κB Pathway Inhibition J. Transl. Med. 2014, 12, 163 10.1186/1479-5876-12-163
20. Cho, H. J.; Lee, T. S.; Park, J. B.; Park, K. K.; Choe, J. Y.; Sin, D. I.; Park, Y. Y.; Moon, Y. S.; Lee, K. G.; Yeo, J. H.; Han, S. M.; Cho, Y. S.; Choi, M. R.; Park, N. G.; Lee, Y. S.; Chang, Y. C. Disulfiram Suppresses Invasive Ability of Osteosarcoma Cells Via the Inhibition of MMP-2 and MMP-9 Expression J. Biochem. Mol. Biol. 2007, 40 (6) 1069-1076 10.5483/BMBRep.2007.40.6.1069
21. Zhang, H.; Chen, D.; Ringler, J.; Chen, W.; Cui, Q. C.; Ethier, S. P.; Dou, Q. P.; Wu, G. Disulfiram Treatment Facilitates Phosphoinositide 3-kinase Inhibition in Human Breast Cancer Cells in vitro and in vivo Cancer Res. 2010, 70 (10) 3996-4004 10.1158/0008-5472.CAN-09-3752
22. Cobby, J.; Mayersohn, M.; Selliah, S. The Rapid Reduction of Disulfiram in Blood and Plasma Life Sci. 1977, 21 (7) 937-941 10.1016/0024-3205(77)90259-4
23. Johansson, B. A Review of the Pharmacokinetics and Pharmacodynamics of Disulfiram and its Metabolites Acta Psychiatr. Scand. 1992, 86 (369) 15-26 10.1111/j.1600-0447.1992.tb03310.x
24. Zhang, L.; Jiang, Y.; Jing, G.; Tang, Y.; Chen, X.; Yang, D.; Zhang, Y.; Tang, X. A Novel UPLC-ESI-MS/MS Method for the Quantitation of Disulfiram, its Role in Stabilized Plasma and its Application. J. chromatogr. B Analyt. Technol. biomed J. Chromatogr. B: Anal. Technol. Biomed. Life Sci. 2013, 937, 54-59 10.1016/j.jchromb.2013.08.009
25. Liu, D.; Zhang, N. Cancer Chemotherapy With Lipid-Based Nanocarriers Crit. Rev. Ther. Drug Carrier Syst. 2010, 27 (5) 371-417 10.1615/CritRevTherDrugCarrierSyst.v27.i5.10
26. Saliou, B.; Thomas, O.; Lautram, N.; Clavreul, A.; Hureaux, J.; Urban, T.; Benoit, J. P.; Lagarce, F. Development and in vitro Evaluation of a Novel Lipid Nanocapsule Formulation of Etoposide Eur. J. Pharm. Sci. 2013, 50 (2) 172-180 10.1016/j.ejps.2013.06.013
27. Garcion, E.; Lamprecht, A.; Heurtault, B.; Paillard, A.; Aubert-Pouessel, A.; Denizot, B.; Menei, P.; Benoit, J. P. A New Generation of Anticancer, Drug-loaded, Colloidal Vectors Reverses Multidrug Resistance in Glioma and Reduces Tumor Progression in Rats Mol. Cancer Ther. 2006, 5 (7) 1710-1722 10.1158/1535-7163.MCT-06-0289
28. Dhanikula, A. B.; Khalid, N. M.; Lee, S. D.; Yeung, R.; Risovic, V.; Wasan, K. M.; Leroux, J. C. Long Circulating Lipid Nanocapsules for Drug Detoxification Biomaterials 2007, 28 (6) 1248-1257 10.1016/j.biomaterials.2006.10.036
29. Morille, M.; Montier, T.; Legras, P.; Carmoy, N.; Brodin, P.; Pitard, B.; Benoit, J. P.; Passirani, C. Long-circulating DNA Lipid Nanocapsules as New Vector for Passive Tumor Targeting Biomaterials 2010, 31 (2) 321-329 10.1016/j.biomaterials.2009.09.044
30. Hirsjarvi, S.; Dufort, S.; Gravier, J.; Texier, I.; Yan, Q.; Bibette, J.; Sancey, L.; Josserand, V.; Passirani, C.; Benoit, J. P.; Coll, J. L. Influence of Size, Surface Coating and Fine Chemical Composition on the in vitro Reactivity and in vivo Biodistribution of Lipid Nanocapsules Versus Lipid Nanoemulsions in Cancer Models Nanomedicine 2013, 9 (3) 375-387 10.1016/j.nano.2012.08.005
31. Hatakeyama, H.; Akita, H.; Harashima, H. A Multifunctional Envelope Type Nano Device (MEND) for Gene Delivery to Tumours Based on the EPR Effect: a Strategy for Overcoming the PEG Dilemma Adv. Drug Delivery Rev. 2011, 63 (3) 152-160 10.1016/j.addr.2010.09.001
32. Wang, S.; Zhang, S.; Liu, J.; Liu, Z.; Su, L.; Wang, H.; Chang, J. pH- and Reduction-responsive Polymeric Lipid Vesicles for Enhanced Tumor Cellular Internalization and Triggered Drug Release ACS Appl. Mater. Interfaces 2014, 6 (13) 10706-10713 10.1021/am502579e
33. Stefanick, J. F.; Ashley, J. D.; Kiziltepe, T.; Bilgicer, B. A Systematic Analysis of Peptide Linker Length and Liposomal Polyethylene Glycol Coating on Cellular Uptake of Peptide-Targeted Liposomes ACS Nano 2013, 7 (4) 2935-2947 10.1021/nn305663e
34. Koren, E.; Torchilin, V. P. Cell-penetrating Peptides: Breaking Through to the Other Side Trends Mol. Med. 2012, 18 (7) 385-393 10.1016/j.molmed.2012.04.012
35. Koren, E.; Apte, A.; Jani, A.; Torchilin, V. P. Multifunctional PEGylated 2C5-immunoliposomes Containing pH-sensitive Bonds and TAT Peptide for Enhanced Tumor Cell Internalization and Cytotoxicity J. Controlled Release 2012, 160 (2) 264-273 10.1016/j.jconrel.2011.12.002
36. Koren, E.; Apte, A.; Sawant, R. R.; Grunwald, J.; Torchilin, V. P. Cell-penetrating TAT Peptide in Drug Delivery Systems: Proteolytic Stability Requirements Drug Delivery 2011, 18 (5) 377-384 10.3109/10717544.2011.567310
37. Apte, A.; Koren, E.; Koshkaryev, A.; Torchilin, V. P. Doxorubicin in TAT Peptide-modified Multifunctional Immunoliposomes Demonstrates Increased Activity Against both Drug-sensitive and Drug-resistant Ovarian Cancer Models Cancer Biol. Ther. 2014, 15 (1) 69-80 10.4161/cbt.26609
38. Huang, P.; Wang, W.; Zhou, J.; Zhao, F.; Zhang, Y.; Liu, J.; Liu, J.; Dong, A.; Kong, D.; Zhang, J. Amphiphilic Polyelectrolyte/prodrug Nanoparticles Constructed by Synergetic Electrostatic and Hydrophobic Interactions with Cooperative pH-sensitivity for Controlled Doxorubicin Delivery ACS Appl. Mater. Interfaces 2015, 7 (11) 6340-6350 10.1021/acsami.5b00962
39. Zhang, W.; Mao, Z.; Gao, C. Preparation of TAT peptide-modified poly(N-isopropylacrylamide) Microgel Particles and Their Cellular Uptake, Intracellular Distribution, and Influence on Cytoviability in Response to Temperature Change J. Colloid Interface Sci. 2014, 434, 122-129 10.1016/j.jcis.2014.07.031
40. Zhu, L.; Kate, P.; Torchilin, V. P. Matrix Metalloprotease 2-responsive Multifunctional Liposomal Nanocarrier for Enhanced Tumor Targeting ACS Nano 2012, 6 (4) 3491-3498 10.1021/nn300524f
41. Boulmedais, F.; Frisch, B.; Etienne, O.; Lavalle, P.; Picart, C.; Ogier, J.; Voegel, J. C.; Schaaf, P.; Egles, C. Polyelectrolyte Multilayer Films with Pegylated Polypeptides as a New Type of Anti-microbial Protection for Biomaterials Biomaterials 2004, 25 (11) 2003-2011 10.1016/j.biomaterials.2003.08.039
42. Guo, S.; Huang, Y.; Zhang, W.; Wang, W.; Wei, T.; Lin, D.; Xing, J.; Deng, L.; Du, Q.; Liang, Z.; Liang, X. J.; Dong, A. Ternary Complexes of Amphiphilic Polycaprolactone-graft-poly (N,N-dimethylaminoethyl methacrylate), DNA and Polyglutamic Acid-graft-poly(ethylene glycol) for Gene Delivery Biomaterials 2011, 32 (18) 4283-4292 10.1016/j.biomaterials.2011.02.034
43. Yang, Z.; Jiang, Z.; Cao, Z.; Zhang, C.; Gao, D.; Luo, X.; Zhang, X.; Luo, H.; Jiang, Q.; Liu, J. Multifunctional Non-viral Gene Vectors with Enhanced Stability, Improved Cellular and Nuclear Uptake Capability, and Increased Transfection Efficiency Nanoscale 2014, 6 (17) 10193-10206 10.1039/C4NR02395A
44. Heurtault, B.; Saulnier, P.; Pech, B.; Proust, J. E.; Benoit, J. P. A Novel Phase Inversion-Based Process for the Preparation of Lipid Nanocarriers Pharm. Res. 2002, 19 (6) 875-880 10.1023/A:1016121319668
45. Heurtault, B.; Saulnier, P.; Pech, B.; Venier-Julienne, M. C.; Proust, J. E.; Phan-Tan-Luu, R.; Benoit, J.-P. The Influence of Lipid Nanocapsule Composition on Their Size Distribution Eur. J. Pharm. Sci. 2003, 18 (1) 55-61 10.1016/S0928-0987(02)00241-5
46. Xu, Y.; Jin, X.; Ping, Q.; Cheng, J.; Sun, M.; Cao, F.; You, W.; Yuan, D. A Novel Lipoprotein-mimic Nanocarrier Composed of the Modified Protein and Lipid for Tumor Cell Targeting Delivery J. Controlled Release 2010, 146 (3) 299-308 10.1016/j.jconrel.2010.05.022
47. Auguste, D. T.; Armes, S. P.; Brzezinska, K. R.; Deming, T. J.; Kohn, J.; Prudhomme, R. K. pH Triggered Release of Protective Poly(ethylene glycol)-b-polycation Copolymers from Liposomes Biomaterials 2006, 27 (12) 2599-2608 10.1016/j.biomaterials.2005.08.036
48. Hu, J.; Miura, S.; Na, K.; Bae, Y. H. pH-responsive and Charge Shielded Cationic Micelle of Poly(L-histidine)-block-short Branched PEI for Acidic Cancer Treatment J. Controlled Release 2013, 172 (1) 69-76 10.1016/j.jconrel.2013.08.007
49. Xu, H.; Cai, C.; Gou, J.; Sui, B.; Jin, J.; Yin, T.; Xu, H.; Zhang, Y.; Wang, L.; Zhai, Y.; Tang, X. Self-Assembled Monomethoxy (Polyethylene Glycol)-b-P(D,L-Lactic-co-Glycolic Acid)-b-P(L-Glutamic Acid) Hybrid-Core Nanoparticles for Intracellular pH-Triggered Release of Doxorubicin J. Biomed. Nanotechnol. 2015, 11 (8) 1354-1369 10.1166/jbn.2015.2088
50. Mattheolabakis, G.; Rigas, B.; Constantinides, P. P. Nanodelivery Strategies in Cancer Chemotherapy: Biological Rationale and Pharmaceutical Perspectives Nanomedicine 2012, 7 (10) 1577-1590 10.2217/nnm.12.128
51. Daniel, K. G.; Chen, D.; Orlu, S.; Cui, Q. C.; Miller, F. R.; Dou, Q. P. Clioquinol and Pyrrolidine Dithiocarbamate Complex with Copper to Form Proteasome Inhibitors and Apoptosis Inducers in Human Breast Cancer Cells Breast Cancer Res. 2005, 7 (6) R897-908 10.1186/bcr1322
52. Lamprecht, A.; Bouligand, Y.; Benoit, J. P. New Lipid Nanocapsules Exhibit Sustained Release Properties for Amiodarone J. Controlled Release 2002, 84 (1-2) 59-68 10.1016/S0168-3659(02)00258-4
53. Ziegler, A.; Seelig, J. Binding and Clustering of Glycosaminoglycans: a Common Property of Mono- and Multivalent Cell-penetrating Compounds Biophys. J. 2008, 94 (6) 2142-2149 10.1529/biophysj.107.113472
54. Schmidt, N.; Mishra, A.; Lai, G. H.; Wong, G. C. Arginine-rich Cell-penetrating Peptides FEBS Lett. 2010, 584 (9) 1806-1813 10.1016/j.febslet.2009.11.046
55. Vonarbourg, A.; Passirani, C.; Saulnier, P.; Benoit, J. P. Parameters Influencing the Stealthiness of Colloidal Drug Delivery Systems Biomaterials 2006, 27 (24) 4356-4373 10.1016/j.biomaterials.2006.03.039
56. Dos Santos, N.; Allen, C.; Doppen, A. M.; Anantha, M.; Cox, K. A.; Gallagher, R. C.; Karlsson, G.; Edwards, K.; Kenner, G.; Samuels, L.; Webb, M. S.; Bally, M. B. Influence of Poly(ethylene glycol) Grafting Density and Polymer Length on Liposomes: Relating Plasma Circulation Lifetimes to Protein Binding Biochim. Biophys. Acta, Biomembr. 2007, 1768 (6) 1367-1377 10.1016/j.bbamem.2006.12.013
57. Abe, K.; Higashi, K.; Watabe, K.; Kobayashi, A.; Limwikrant, W.; Yamamoto, K.; Moribe, K. Effects of the PEG Molecular Weight of a PEG-lipid and Cholesterol on PEG Chain Flexibility on Liposome Surfaces Colloids Surf., A 2015, 474, 63-70 10.1016/j.colsurfa.2015.03.006
58. Yang, Q.; Jones, S. W.; Parker, C. L.; Zamboni, W. C.; Bear, J. E.; Lai, S. K. Evading Immune Cell Uptake and Clearance Requires PEG Grafting at Densities Substantially Exceeding the Minimum for Brush Conformation Mol. Pharmaceutics 2014, 11 (4) 1250-1258 10.1021/mp400703d
59. Kuai, R.; Yuan, W.; Li, W.; Qin, Y.; Tang, J.; Yuan, M.; Fu, L.; Ran, R.; Zhang, Z.; He, Q. Targeted Delivery of Cargoes into a Murine Solid Tumor by a Cell-penetrating Peptide and Cleavable Poly(ethylene glycol) Comodified Liposomal Delivery System via Systemic Administration Mol. Pharmaceutics 2011, 8 (6) 2151-2161 10.1021/mp200100f
60. Wang, Y.; Zhou, J.; Qiu, L.; Wang, X.; Chen, L.; Liu, T.; Di, W. Cisplatin-alginate conjugate liposomes for targeted delivery to EGFR-positive ovarian cancer cells Biomaterials 2014, 35 (14) 4297-4309 10.1016/j.biomaterials.2014.01.035