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Synthesis And Biological Evaluation Of Dual Functionalized Glutathione Sensitive Poly(ester-urethane) Multiblock Polymeric Nanoparticles For Cancer Targeted Drug Delivery

Arun N Kumar, A. Kumar, S. V. Lale, S. V. Lale, Farhat Naz, V. Choudhary, V. Koul, V. Koul
Published 2015 · Chemistry

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Glutathione sensitive polymeric nanoparticles composed of poly(ester-urethane) and (-PCL-PEG-PCL-urethane-ss-) random multiblock copolymers with multiple disulfide linkages were developed for targeted doxorubicin delivery in cancer. The multiblock copolymers were synthesized via ring opening polymerization (ROP) of e-caprolactone by polyethylene glycol followed by isomerization polymerization with hexamethylene diisocyanate (HMDI) and 2-hydroxyethyl disulfide. The polyethylene glycol (PEG) content of ∼20% in the multiblock copolymers led to the formation of nanoparticles with size ∼80 nm. A high doxorubicin loading content of ∼26% was achieved in the polymeric nanoparticles. Disulfide linkages in the multiblock copolymers facilitate nanoparticle degradation by glutathione (GSH), resulting in intracellular drug release. Drug release studies confirmed the glutathione sensitive nature of polymeric nanosystems by achieving ∼80% drug release at pH 5.5 in the presence of 10 mM GSH concentration as compared to ∼19% at pH 7.4. In vitro studies in breast cancer cell lines (MCF-7 and BT474) showed a ∼20 fold increase in cellular uptake efficiency of dual targeted nanoparticles with a subsequent higher apoptosis as compared to non-targeted polymeric nanoparticles. In vivo studies in Ehrlich's ascites tumor (EAT) bearing Swiss albino mice showed a superior tumor regression of ∼89% as compared to free doxorubicin (∼42%) without any significant toxicity. These promising results show the potential of the above synthesized multiblock copolymeric nanosystem as a drug delivery nanocarrier in cancer therapeutics with an enhanced antitumor efficacy and a reduced toxicity.
This paper references
10.1002/JPS.20627
In vitro hemolysis: guidance for the pharmaceutical scientist.
K. Amin (2006)
10.1039/c4bm00462k
Folate-containing reduction-sensitive lipid-polymer hybrid nanoparticles for targeted delivery of doxorubicin.
B. Wu (2015)
10.1021/am405927f
Controlled release of protein from biodegradable multi-sensitive injectable poly(ether-urethane) hydrogel.
X. Li (2014)
10.1016/0378-5173(89)90281-0
Nanocapsule formation by interfacial polymer deposition following solvent displacement
H. Fessi (1989)
10.1021/bm5003009
Ligand-directed active tumor-targeting polymeric nanoparticles for cancer chemotherapy.
Yinan Zhong (2014)
10.1016/j.ejpb.2015.03.018
Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy.
Edgar Pérez-Herrero (2015)
10.1021/bm301894z
Polymer-coated echogenic lipid nanoparticles with dual release triggers.
Rahul R. Nahire (2013)
10.1021/BC990092L
Poly(ethylene glycol) multiblock copolymer as a carrier of anti-cancer drug doxorubicin.
M. Pechar (2000)
10.1021/MA034006V
Synthesis and Characterization of Poly(l-lactide)−Poly(ε-caprolactone) Multiblock Copolymers
O. Jeon (2003)
10.1002/JBM.1242
Biodegradable poly(ethylene oxide)/poly(epsilon-caprolactone) multiblock copolymers.
D. Cohn (2002)
10.1039/C1SM05080J
Sustained delivery of doxorubicin using biodegradable pH/temperature-sensitive poly(ethylene glycol)-poly(β-amino ester urethane) multiblock copolymer hydrogels
C. Huynh (2011)
10.1021/bm5008508
Glutathione-triggered disassembly of dual disulfide located degradable nanocarriers of polylactide-based block copolymers for rapid drug release.
N. R. Ko (2014)
10.1021/MA010986C
Kinetics and Mechanism of the Stannous Octoate-Catalyzed Bulk Polymerization of ∊-Caprolactone
Robson F. Storey (2002)
10.4314/AJB.V10I13
Ehrlich ascites carcinoma
M. Ozaslan (2011)
10.1016/S0736-4679(98)00129-2
Creatine kinase and its CK-MB isoenzyme: the conventional marker for the diagnosis of acute myocardial infarction.
D. Robinson (1999)
10.1021/MA060153S
Gelation Behavior of Poly(ethylene glycol) and Polycaprolactone Triblock and Multiblock Copolymer Aqueous Solutions
S. J. Bae (2006)
10.1039/c4ob00164h
Recent advances in biocompatible nanocarriers for delivery of chemotherapeutic cargoes towards cancer therapy.
C. Ang (2014)
10.1016/j.jconrel.2014.12.030
Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications.
A. Wicki (2015)
10.1016/j.breast.2013.11.011
Treatment of HER2-positive breast cancer.
Maria Cristina Figueroa-Magalhães (2014)
10.1021/MA010005W
Synthesis of Star-Shaped Poly(ε-caprolactone)-b-poly(dl-lactic acid-alt-glycolic acid) with Multifunctional Initiator and Stannous Octoate Catalyst
Chang-Ming Dong (2001)
10.1016/j.addr.2013.11.009
Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology.
N. Bertrand (2014)
10.1039/C3PY01384G
Recent trends in the design of anticancer polymer prodrug nanocarriers
Vianney Delplace (2014)
10.1021/acsami.5b01731
ROP and ATRP Fabricated Dual Targeted Redox Sensitive Polymersomes Based on pPEGMA-PCL-ss-PCL-pPEGMA Triblock Copolymers for Breast Cancer Therapeutics.
Arun Kumar (2015)
10.1039/C3TB20191K
Polymeric theranostics: using polymer-based systems for simultaneous imaging and therapy.
T. Krasia-Christoforou (2013)
10.1039/C0PY00376J
Effect of PEG content on the properties of biodegradable amphiphilic multiblock poly(ε-caprolactone urethane)s
M. Ding (2011)
10.1016/J.EJPS.2005.08.012
Biodegradable thermo-sensitive nanoparticles from poly(L-lactic acid)/poly(ethylene glycol) alternating multi-block copolymer for potential anti-cancer drug carrier.
K. Na (2006)
10.1016/j.biomaterials.2014.06.036
Actively targeted delivery of anticancer drug to tumor cells by redox-responsive star-shaped micelles.
Chunli Shi (2014)
10.1016/j.jconrel.2010.07.123
A simple method to achieve high doxorubicin loading in biodegradable polymersomes.
Charles Sanson (2010)
10.1016/0022-1759(83)90303-4
Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.
T. Mosmann (1983)
10.1039/c0nr00821d
Folate receptor targeted, carboxymethyl chitosan functionalized iron oxide nanoparticles: a novel ultradispersed nanoconjugates for bimodal imaging.
D. Bhattacharya (2011)
10.1002/adhm.201300308
Disulfide cross-linked polyurethane micelles as a reduction-triggered drug delivery system for cancer therapy.
Shuangjiang Yu (2014)
10.1039/C3PY01192E
Redox-responsive polymers for drug delivery: from molecular design to applications
Meng Huo (2014)
10.1039/C4PY01698J
Multifunctional ATRP based pH responsive polymeric nanoparticles for improved doxorubicin chemotherapy in breast cancer by proton sponge effect/endo-lysosomal escape
S. V. Lale (2015)
10.1039/C2SM27616J
pH and reduction dual responsive polyurethane triblock copolymers for efficient intracellular drug delivery
Shuangjiang Yu (2013)
10.1038/nnano.2007.387
Nanocarriers as an emerging platform for cancer therapy.
D. Peer (2007)
10.1021/bm5001263
AS1411 aptamer and folic acid functionalized pH-responsive ATRP fabricated pPEGMA-PCL-pPEGMA polymeric nanoparticles for targeted drug delivery in cancer therapy.
S. V. Lale (2014)
10.1021/JS970184O
Lysis of human red blood cells. 4. Comparison of in vitro and in vivo hemolysis data.
J. Krzyzaniak (1997)
10.1021/acs.biomac.5b00244
Folic Acid and Trastuzumab Functionalized Redox Responsive Polymersomes for Intracellular Doxorubicin Delivery in Breast Cancer.
S. V. Lale (2015)
10.1021/bm401098w
Ligand-directed reduction-sensitive shell-sheddable biodegradable micelles actively deliver doxorubicin into the nuclei of target cancer cells.
Yinan Zhong (2013)
10.1039/c5bm00002e
Trigger responsive polymeric nanocarriers for cancer therapy.
Shahdeep Kaur (2015)
10.1016/j.tibtech.2013.10.004
The potential legacy of cancer nanotechnology: cellular selection.
H. Patra (2014)
10.1021/bm201479t
Block copolymer micelles target Auger electron radiotherapy to the nucleus of HER2-positive breast cancer cells.
Bryan Hoang (2012)
10.1016/J.EJPB.2006.11.009
A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures: micelles, nanospheres, nanocapsules and polymersomes.
K. Letchford (2007)
10.1039/C4PY00538D
Galactosylated reduction and pH dual-responsive triblock terpolymer Gal-PEEP-a-PCL-ss-PDMAEMA: a multifunctional carrier for the targeted and simultaneous delivery of doxorubicin and DNA
Y. Zhang (2014)
10.1016/j.actbio.2013.08.015
Doxorubicin-loaded amphiphilic polypeptide-based nanoparticles as an efficient drug delivery system for cancer therapy.
Shixian Lv (2013)
10.1039/C3PY00991B
Glutathione-triggered disassembly of isothermally responsive polymer nanoparticles obtained by nanoprecipitation of hydrophilic polymers
D. J. Phillips (2014)
10.1016/S0927-7765(99)00156-3
'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.
Gref (2000)
10.1016/j.colsurfb.2015.03.040
Reduction-sensitive micelles with sheddable PEG shells self-assembled from a Y-shaped amphiphilic polymer for intracellular doxorubicine release.
C. Cui (2015)



This paper is referenced by
10.1016/j.saa.2019.117654
Intrinsically ESIPT-exhibiting and enhanced emission in polymer nanoparticles as signaling for sensing nitrite.
Q. Wang (2019)
10.1021/acsami.7b18887
Folate-Conjugated Polyphosphoester with Reversible Cross-Linkage and Reduction Sensitivity for Drug Delivery.
Youwen Cao (2018)
10.2147/IJN.S198217
Elaboration and characterization of curcumin-loaded Tri-CL-mPEG three-arm copolymeric nanoparticles by a microchannel technology
W. Wu (2019)
10.1016/j.msec.2017.03.124
Folate-decorated PEGylated triblock copolymer as a pH/reduction dual-responsive nanovehicle for targeted intracellular co-delivery of doxorubicin and Bcl-2 siRNA.
A. Suo (2017)
10.1016/j.ijpharm.2020.119781
Stimuli-responsive biodegradable polyurethane nano-constructs as a potential triggered drug delivery vehicle for cancer therapy.
K. R. Gajbhiye (2020)
10.3390/ijms21176018
Antibody Conjugation of Nanoparticles as Therapeutics for Breast Cancer Treatment
A. Juan (2020)
10.1039/C6PY00326E
Synthesis and micellization of redox-responsive dynamic covalent multi-block copolymers
W. Hu (2016)
10.1016/j.msec.2018.06.044
Synthesis and biological evaluation of redox/NIR dual stimulus-responsive polymeric nanoparticles for targeted delivery of cisplatin.
Chaoqun You (2018)
10.1016/j.colsurfb.2016.10.044
Folic acid and trastuzumab conjugated redox responsive random multiblock copolymeric nanocarriers for breast cancer therapy: In-vitro and in-vivo studies.
Arun Kumar (2017)
10.1007/978-981-10-3647-7_2
The Development and Achievement of Polymeric Nanoparticles for Cancer Drug Treatment
Wing-Hin Lee (2017)
10.1002/PI.5618
Polyurethane/doxorubicin nanoparticles based on electrostatic interactions as pH‐sensitive drug delivery carriers
Dengcheng Huang (2018)
10.1016/j.lfs.2019.117137
Synthesis and biological evaluation of surface-modified nanocellulose hydrogel loaded with paclitaxel.
Like Ning (2019)
10.1016/j.msec.2017.03.024
Combinatorial delivery of superparamagnetic iron oxide nanoparticles (γFe2O3) and doxorubicin using folate conjugated redox sensitive multiblock polymeric nanocarriers for enhancing the chemotherapeutic efficacy in cancer cells.
Chetan Nehate (2017)
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