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Synthesis And Evaluation Of Cholesterol-grafted PEGylated Peptides With PH-triggered Property As Novel Drug Carriers For Cancer Chemotherapy.

C. Zhang, Quan Chen, W. Wu, Xin Guo, C. Z. Cai, L. Zhang
Published 2016 · Chemistry, Medicine

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Multifunctional core/shell micelles were self-assembled from triblock copolymers poly(ethylene glycol) methyl ether-b-peptide-g-cholesterol (mPEG-b-P-g-Chol) and used as the doxorubicin delivery carriers for cancer chemotherapy. The copolymers were designed and synthesized successfully based on peptides containing histidine residues (pH-trigger) with different topological structures. The peptides were modified by mPEG (hydrophilic) and cholesterol motifs (hydrophobic) on the terminus, resulting in pH-sensitive amphiphilic copolymers. The critical micelle concentrations (CMCs) of the micelles were determined as 4.79, 2.50 and 1.86mg/L for the linear, Y-shape and fork-shape copolymers, respectively, demonstrating the formation of micelle even at low concentration. The pKb values of three copolymers were found to be around 6.1-6.3 by potentiometric titration test, showing the satisfied pH-sensitivity. The average diameter and zeta potential of blank micelles were 170nm and +20mV at pH 7.4, and increased to 250nm and +35mV at pH 5.0. DOX was loaded into the core of polymeric micelles by dialysis method, and the drug loading capacity slightly increased when the copolymer topological structure changed from linear to Y- and fork-shape. The drug release rate from the system was obviously influencing by the pH values according to the results of in vitro DOX release experiment. Moreover, to investigate the structure-property relationship, the drug release mechanism was preliminarily explored by the semi-empirical equations. Toxicity test showed that three copolymers had bare toxicity whereas the DOX-loaded micelles remained high cytotoxicity for tumor cells. The results indicate the synthesized copolymers might be a potential hydrophobic drug delivery carrier for cancer targeting therapy with controlled drug release.
This paper references
10.1016/S0169-409X(01)00112-0
Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC).
J. Siepmann. (2001)
10.1021/NL0479987
Super pH-sensitive multifunctional polymeric micelle.
E. Lee (2005)
10.1166/JNN.2015.10298
Applications of Nanoparticles for Anticancer Drug Delivery: A Review.
Yuanyuan Zhu (2015)
10.1002/adma.201303123
MSN anti-cancer nanomedicines: chemotherapy enhancement, overcoming of drug resistance, and metastasis inhibition.
Q. He (2014)
10.1021/MP0500420
Poly(ethylene oxide)-modified poly(beta-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs. 1. In vitro evaluations.
D. Shenoy (2005)
10.1016/j.actbio.2012.08.049
Smart nanocarriers for pH-triggered targeting and release of hydrophobic drugs.
S. Cajot (2012)
10.1038/nmat2608
Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging.
P. Horcajada (2010)
10.1021/MA2023414
Periodically Grafted Amphiphilic Copolymers: Nonionic Analogues of Ionenes
R. K. Roy (2012)
10.1016/j.colsurfb.2014.06.054
Novel biocompatible pH-stimuli responsive superparamagnetic hybrid hollow microspheres as tumor-specific drug delivery system.
X. Li (2014)
10.1021/mp300702x
Single-antibody, targeted nanoparticle delivery of camptothecin.
Han Han (2013)
10.1016/j.jconrel.2014.05.048
Selective intracellular delivery of proteasome inhibitors through pH-sensitive polymeric micelles directed to efficient antitumor therapy.
S. Quader (2014)
10.1016/j.tips.2009.08.004
Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer.
Y. Malam (2009)
10.1016/j.ijpharm.2015.01.009
Paclitaxel-loaded micelles enhance transvascular permeability and retention of nanomedicines in tumors.
F. Danhier (2015)
10.1016/j.jconrel.2013.04.026
Biodegradable hybrid polymer micelles for combination drug therapy in ovarian cancer.
S. Desale (2013)
10.1039/c2nr32923a
Cholesterol--a biological compound as a building block in bionanotechnology.
L. Hosta-Rigau (2013)
10.1002/ADFM.201400015
Novel insights into combating cancer chemotherapy resistance using a plasmonic nanocarrier: Enhancing drug sensitiveness and accumulation simultaneously with localized mild photothermal stimulus of femtosecond pulsed laser
L. Wang (2014)
10.1016/j.nano.2008.09.003
Degradable poly(beta-amino ester) nanoparticles for cancer cytoplasmic drug delivery.
Youqing Shen (2009)
10.1021/ab500084g
Nanotherapy for Cancer: Targeting and Multifunctionality in the Future of Cancer Therapies
A. Ediriwickrema (2015)
10.1021/la404488n
Size control of core-shell-type polymeric micelle with a nanometer precision.
A. Makino (2014)
10.1021/AB500088B
Multiple PEG Chains Attached onto the Surface of a Helix Bundle: Conformations and Implications
E. Hamed (2015)
10.1038/nmat3788
Translating materials design to the clinic.
J. Hubbell (2013)
10.1021/nn402657d
Development of poly(β-amino ester)-based biodegradable nanoparticles for nonviral delivery of minicircle DNA.
M. Keeney (2013)
10.1002/1521-3773(20010504)40:9<1707::AID-ANIE17070>3.0.CO;2-F
pH-Responsive Polymer Microspheres: Rapid Release of Encapsulated Material within the Range of Intracellular pH**
D. Lynn (2001)
10.1016/j.biomaterials.2014.04.072
Polymeric micelles for GSH-triggered delivery of arsenic species to cancer cells.
Q. Zhang (2014)
10.1002/adhm.201200154
PEGylated peptide based reductive polycations as efficient nonviral gene vectors.
J. Yang (2013)
10.1126/SCIENCE.1095833
Drug Delivery Systems: Entering the Mainstream
T. Allen (2004)
10.1021/am100860b
Microfluidic melt emulsification for encapsulation and release of actives.
B. Sun (2010)
10.1111/j.2042-7158.2012.01567.x
Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems
Oktay Tacar (2013)
10.1039/C4PY00575A
Tumor-targeted aggregation of pH-sensitive nanocarriers for enhanced retention and rapid intracellular drug release
W. Wu (2014)
10.1021/ab500179h
Design strategies and applications of circulating cell-mediated drug delivery systems.
Yixue Su (2015)
10.1016/S0168-3659(03)00205-0
Poly(L-histidine)-PEG block copolymer micelles and pH-induced destabilization.
E. Lee (2003)
10.1038/nrm2336
Cellular cholesterol trafficking and compartmentalization
E. Ikonen (2008)
10.1039/c4bm00410h
pH- and redox-responsive self-assembly of amphiphilic hyperbranched poly(amido amine)s for controlled doxorubicin delivery.
Weiren Cheng (2015)
10.1039/b915139g
Designing multifunctional quantum dots for bioimaging, detection, and drug delivery.
P. Zrazhevskiy (2010)
10.1016/j.jconrel.2010.02.024
Tumoral acidic pH-responsive MPEG-poly(beta-amino ester) polymeric micelles for cancer targeting therapy.
Kyung Hyun Min (2010)
10.1021/ACSBIOMATERIALS.5B00119
Glutathione-Responsive Polymeric Micelles Formed by a Biodegradable Amphiphilic Triblock Copolymer for Anticancer Drug Delivery and Controlled Release
Zhigang Xu (2015)
10.1021/bm300985r
pH-Sensitive polymeric micelle-based pH probe for detecting and imaging acidic biological environments.
Y. Lee (2012)
10.1002/adhm.201200313
Stimulus-sensitive polymeric nanoparticles and their applications as drug and gene carriers.
Y. Li (2013)
10.1002/smll.200701275
Doxorubicin-loaded polymeric micelle overcomes multidrug resistance of cancer by double-targeting folate receptor and early endosomal pH.
D. Kim (2008)
10.1158/0008-5472.CAN-07-6611
A history of cancer chemotherapy.
V. Devita (2008)
10.1016/j.jconrel.2015.03.018
Selective redox-responsive drug release in tumor cells mediated by chitosan based glycolipid-like nanocarrier.
Ying-wen Hu (2015)
10.1016/J.ADDR.2006.09.007
Mathematical modeling and simulation of drug release from microspheres: Implications to drug delivery systems.
D. Y. Arifin (2006)
10.1021/nn404501g
Facing the truth about nanotechnology in drug delivery.
K. Park (2013)
10.1002/AIC.12119
Core/shell pH‐sensitive micelles self‐assembled from cholesterol conjugated oligopeptides for anticancer drug delivery
Xin Guo (2009)
10.1016/j.biomaterials.2014.03.046
pH-responsive polymer-liposomes for intracellular drug delivery and tumor extracellular matrix switched-on targeted cancer therapy.
Yi-Ting Chiang (2014)
10.1007/s11095-006-0022-2
Enhanced Oral Paclitaxel Bioavailability After Administration of Paclitaxel-Loaded Lipid Nanocapsules
S. Peltier (2006)
10.1016/j.colsurfb.2015.07.008
Folate-polydiacetylene-liposome for tumor targeted drug delivery and fluorescent tracing.
Lielie Li (2015)
10.1016/j.biomaterials.2012.05.025
Self-assembled pH-responsive MPEG-b-(PLA-co-PAE) block copolymer micelles for anticancer drug delivery.
C. Zhang (2012)
10.1002/ADFM.201404122
On-Chip Self-Assembly of a Smart Hybrid Nanocomposite for Antitumoral Applications
B. Herranz-Blanco (2015)
10.1039/c2cs15344k
Targeted polymeric therapeutic nanoparticles: design, development and clinical translation.
Nazila Kamaly (2012)
10.3109/1061186X.2014.936870
3-Methyladenine can depress drug efflux transporters via blocking the PI3K–AKT–mTOR pathway thus sensitizing MDR cancer to chemotherapy
Zhenyou Zou (2014)
10.1021/mp400778r
Combinational Delivery of Hydrophobic and Hydrophilic Anticancer Drugs in Single Nanoemulsions To Treat MDR in Cancer
Y. Ma (2014)
10.1016/J.IJPHARM.2005.05.025
Physicochemical characterization and mechanisms of release of theophylline from melt-extruded dosage forms based on a methacrylic acid copolymer.
C. R. Young (2005)
10.1126/science.1252043
Structural basis for a pH-sensitive calcium leak across membranes
Y. Chang (2014)
10.1002/anie.201101005
High-contrast fluorescence imaging of tumors in vivo using nanoparticles of amphiphilic brush-like copolymers produced by ROMP.
K. Miki (2011)
10.1016/j.colsurfb.2015.07.065
Selective intracellular drug delivery from pH-responsive polyion complex micelle for enhanced malignancy suppression in vivo.
Ji-xue Wang (2015)
10.1039/B714741D
pH-Responsive polymers: synthesis, properties and applications.
S. Dai (2008)
10.1083/JCB.108.4.1291
Acidification of endosome subpopulations in wild-type Chinese hamster ovary cells and temperature-sensitive acidification-defective mutants
S. Schmid (1989)
10.1088/0957-4484/21/26/265601
Self-assembled nanoparticles of cholesterol-conjugated carboxymethyl curdlan as a novel carrier of epirubicin.
L. Li (2010)



This paper is referenced by
10.1098/rsos.171654
pH-responsive polymeric micelles self-assembled from amphiphilic copolymer modified with lipid used as doxorubicin delivery carriers
X. Zhou (2018)
10.1016/j.colsurfb.2019.110443
Smart pH-responsive polymeric micelles for programmed oral delivery of insulin.
Wen Hu (2019)
10.1080/09205063.2020.1747044
Preparation and characterization of Keratin-PEG conjugate-based micelles as a tumor microenvironment-responsive drug delivery system
J. Du (2020)
10.1080/10717544.2019.1709922
Layer-by-layer pH-sensitive nanoparticles for drug delivery and controlled release with improved therapeutic efficacy in vivo
Wan-fu Men (2020)
10.1021/acsnano.8b01422
Structure-Stability-Function Mechanistic Links in the Anti-Measles Virus Action of Tocopherol-Derivatized Peptide Nanoparticles.
T. N. Figueira (2018)
10.1007/s11706-017-0401-0
Folate-conjugated pH-responsive nanocarrier designed for active tumor targeting and controlled release of doxorubicin
Lulu Wei (2017)
10.2147/IJN.S226798
Fabrication Of Dual pH/redox-Responsive Lipid-Polymer Hybrid Nanoparticles For Anticancer Drug Delivery And Controlled Release
Wanfu Men (2019)
10.1016/J.CEJ.2018.02.055
Dual redox/pH-responsive hybrid polymer-lipid composites: Synthesis, preparation, characterization and application in drug delivery with enhanced therapeutic efficacy
J. Li (2018)
10.1016/j.colsurfb.2017.01.033
Computer simulations on the pH-sensitive tri-block copolymer containing zwitterionic sulfobetaine as a novel anti-cancer drug carrier.
Wenfeng Min (2017)
Design of micelle embedded chitosan nanocomposites for targeted delivery of hydrophobic drugs
Esra Cihan (2016)
10.15171/bi.2018.27
Effect of PEGylation on assembly morphology and cellular uptake of poly ethyleneimine-cholesterol conjugates for delivery of sorafenib tosylate in hepatocellular carcinoma
M. Monajati (2018)
10.1016/j.colsurfb.2017.08.018
Highly cell-penetrating and ultra-pH-responsive nanoplatform for controlled drug release and enhanced tumor therapy.
Yong-E Gao (2017)
10.1016/j.actbio.2019.06.051
Low density lipoprotein-inspired nanostructured lipid nanoparticles containing pro-doxorubicin to enhance tumor-targeted therapeutic efficiency.
W. Li (2019)
Multi-Approach Design and Fabrication of Hybrid Composites for Drug Delivery and Cancer Therapy
Bárbara Herranz Blanco (2016)
10.1016/j.bmc.2018.01.012
Peptide chemistry toolbox - Transforming natural peptides into peptide therapeutics.
Miloš Erak (2018)
10.1039/C6RA19552K
Peptide-conjugated PEGylated PAMAM as a highly affinitive nanocarrier towards HER2-overexpressing cancer cells
Iman Rostami (2016)
10.3390/pharmaceutics11040176
Dual pH/Redox-Responsive Mixed Polymeric Micelles for Anticancer Drug Delivery and Controlled Release
Yongle Luo (2019)
10.3390/molecules25184330
The Efficacy of Cholesterol-Based Carriers in Drug Delivery
Ngonidzashe Ruwizhi (2020)
10.1134/S0036024420080294
Synthesis, Morphology, and Spectral Characteristics of Copper, Silver, and Selenium-Containing Hybrid Nanosystems Based on 2-Deoxy-2-metacrylamido-D-glucose Copolymer with 2-Dimethylaminoethyl Methacrylate
S. V. Valueva (2020)
10.1177/0885328217751247
Synthesis, characterization, and property of biodegradable PEG-PCL-PLA terpolymers with miktoarm star and triblock architectures as drug carriers
Y. Zhang (2018)
10.1016/j.msec.2018.04.036
A pH-responsive prodrug delivery system self-assembled from acid-labile doxorubicin-conjugated amphiphilic pH-sensitive block copolymers.
Xiangxuan Huang (2018)
10.1016/j.colsurfb.2019.06.043
Mesoscopic simulations of drug-loaded diselenide crosslinked micelles: Stability, drug loading and release properties.
W. Lin (2019)
10.1039/C6TB03211G
Design and construction of self-hidden and pH-reversed targeting drug delivery nanovehicles via noncovalent interactions to overcome drug resistance.
D. Zhao (2017)
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