← Back to Search
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
Download PDFAnalyze on Scholarcy
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
In vitro hemolysis: guidance for the pharmaceutical scientist.
K. Amin (2006)
Folate-containing reduction-sensitive lipid-polymer hybrid nanoparticles for targeted delivery of doxorubicin.
B. Wu (2015)
Controlled release of protein from biodegradable multi-sensitive injectable poly(ether-urethane) hydrogel.
X. Li (2014)
Nanocapsule formation by interfacial polymer deposition following solvent displacement
H. Fessi (1989)
Ligand-directed active tumor-targeting polymeric nanoparticles for cancer chemotherapy.
Yinan Zhong (2014)
Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy.
Edgar Pérez-Herrero (2015)
Polymer-coated echogenic lipid nanoparticles with dual release triggers.
Rahul R. Nahire (2013)
Poly(ethylene glycol) multiblock copolymer as a carrier of anti-cancer drug doxorubicin.
M. Pechar (2000)
Synthesis and Characterization of Poly(l-lactide)−Poly(ε-caprolactone) Multiblock Copolymers
O. Jeon (2003)
Biodegradable poly(ethylene oxide)/poly(epsilon-caprolactone) multiblock copolymers.
D. Cohn (2002)
Sustained delivery of doxorubicin using biodegradable pH/temperature-sensitive poly(ethylene glycol)-poly(β-amino ester urethane) multiblock copolymer hydrogels
C. Huynh (2011)
Glutathione-triggered disassembly of dual disulfide located degradable nanocarriers of polylactide-based block copolymers for rapid drug release.
N. R. Ko (2014)
Kinetics and Mechanism of the Stannous Octoate-Catalyzed Bulk Polymerization of ∊-Caprolactone
Robson F. Storey (2002)
Ehrlich ascites carcinoma
M. Ozaslan (2011)
Creatine kinase and its CK-MB isoenzyme: the conventional marker for the diagnosis of acute myocardial infarction.
D. Robinson (1999)
Gelation Behavior of Poly(ethylene glycol) and Polycaprolactone Triblock and Multiblock Copolymer Aqueous Solutions
S. J. Bae (2006)
Recent advances in biocompatible nanocarriers for delivery of chemotherapeutic cargoes towards cancer therapy.
C. Ang (2014)
Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications.
A. Wicki (2015)
Treatment of HER2-positive breast cancer.
Maria Cristina Figueroa-Magalhães (2014)
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)
Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology.
N. Bertrand (2014)
Recent trends in the design of anticancer polymer prodrug nanocarriers
Vianney Delplace (2014)
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)
Polymeric theranostics: using polymer-based systems for simultaneous imaging and therapy.
T. Krasia-Christoforou (2013)
Effect of PEG content on the properties of biodegradable amphiphilic multiblock poly(ε-caprolactone urethane)s
M. Ding (2011)
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)
Actively targeted delivery of anticancer drug to tumor cells by redox-responsive star-shaped micelles.
Chunli Shi (2014)
A simple method to achieve high doxorubicin loading in biodegradable polymersomes.
Charles Sanson (2010)
Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.
T. Mosmann (1983)
Folate receptor targeted, carboxymethyl chitosan functionalized iron oxide nanoparticles: a novel ultradispersed nanoconjugates for bimodal imaging.
D. Bhattacharya (2011)
Disulfide cross-linked polyurethane micelles as a reduction-triggered drug delivery system for cancer therapy.
Shuangjiang Yu (2014)
Redox-responsive polymers for drug delivery: from molecular design to applications
Meng Huo (2014)
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)
pH and reduction dual responsive polyurethane triblock copolymers for efficient intracellular drug delivery
Shuangjiang Yu (2013)
Nanocarriers as an emerging platform for cancer therapy.
D. Peer (2007)
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)
Lysis of human red blood cells. 4. Comparison of in vitro and in vivo hemolysis data.
J. Krzyzaniak (1997)
Folic Acid and Trastuzumab Functionalized Redox Responsive Polymersomes for Intracellular Doxorubicin Delivery in Breast Cancer.
S. V. Lale (2015)
Ligand-directed reduction-sensitive shell-sheddable biodegradable micelles actively deliver doxorubicin into the nuclei of target cancer cells.
Yinan Zhong (2013)
Trigger responsive polymeric nanocarriers for cancer therapy.
Shahdeep Kaur (2015)
The potential legacy of cancer nanotechnology: cellular selection.
H. Patra (2014)
Block copolymer micelles target Auger electron radiotherapy to the nucleus of HER2-positive breast cancer cells.
Bryan Hoang (2012)
A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures: micelles, nanospheres, nanocapsules and polymersomes.
K. Letchford (2007)
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)
Doxorubicin-loaded amphiphilic polypeptide-based nanoparticles as an efficient drug delivery system for cancer therapy.
Shixian Lv (2013)
Glutathione-triggered disassembly of isothermally responsive polymer nanoparticles obtained by nanoprecipitation of hydrophilic polymers
D. J. Phillips (2014)
'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.
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
Intrinsically ESIPT-exhibiting and enhanced emission in polymer nanoparticles as signaling for sensing nitrite.
Q. Wang (2019)
Folate-Conjugated Polyphosphoester with Reversible Cross-Linkage and Reduction Sensitivity for Drug Delivery.
Youwen Cao (2018)
Elaboration and characterization of curcumin-loaded Tri-CL-mPEG three-arm copolymeric nanoparticles by a microchannel technology
W. Wu (2019)
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)
Stimuli-responsive biodegradable polyurethane nano-constructs as a potential triggered drug delivery vehicle for cancer therapy.
K. R. Gajbhiye (2020)
Antibody Conjugation of Nanoparticles as Therapeutics for Breast Cancer Treatment
A. Juan (2020)
Synthesis and micellization of redox-responsive dynamic covalent multi-block copolymers
W. Hu (2016)
Synthesis and biological evaluation of redox/NIR dual stimulus-responsive polymeric nanoparticles for targeted delivery of cisplatin.
Chaoqun You (2018)
Folic acid and trastuzumab conjugated redox responsive random multiblock copolymeric nanocarriers for breast cancer therapy: In-vitro and in-vivo studies.
Arun Kumar (2017)
The Development and Achievement of Polymeric Nanoparticles for Cancer Drug Treatment
Wing-Hin Lee (2017)
Polyurethane/doxorubicin nanoparticles based on electrostatic interactions as pH‐sensitive drug delivery carriers
Dengcheng Huang (2018)
Synthesis and biological evaluation of surface-modified nanocellulose hydrogel loaded with paclitaxel.
Like Ning (2019)
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)