Online citations, reference lists, and bibliographies.
← Back to Search

Surface-engineered Dendrimers For Dual Drug Delivery: A Receptor Up-regulation And Enhanced Cancer Targeting Strategy

Rakesh K Tekade, T. Dutta, A. Tyagi, A. Bharti, B. Das, N. K. Jain
Published 2008 · Chemistry

Cite This
Download PDF
Analyze on Scholarcy
Share
The present study is aimed at developing and evaluating a combined strategy of dual drug delivery, receptor up-regulation, and drug targeting. The dendritic architectures were synthesized and characterized by IR, 1H-NMR, and 13C-NMR spectroscopy. The pH-responsive simultaneous release behavior of the loaded bioactive from the carrier was also explored. The cell line studies for MTT cytotoxicity, receptor blockade, and receptor up-regulation assays were performed on HeLa cells. Treatment of cells with low concentration of all-trans retinoic acid (ATRA, ∼1 μM) caused a selective up-regulation of folate receptors by 2.21-folds when compared with that of untreated control, after 48 h. ATRA showed a lag phase of 12 h in up-regulating the folate receptors. After 48 h, the IC50 value of naked methotrexate (MTX)–ATRA combination and dendrimer-loaded MTX–ATRA combination were found to be ∼0.1 and 10 μM, respectively, while folate-anchored dendrimer loaded with MTX–ATRA showed a selectively lowered IC50 value of 0.04 μM. It was concluded that in allied ailments like cancer, the proposed dual-drug delivery modality bearing anti-cancer bioactive in conjunction with folate receptor up-regulating cargo may prove to be a promising approach toward the development of a flourishing cancer therapy.
This paper references
Peptidemediated release of folate-targeted liposome contents from endosomal compartments
K Vogel (1996)
10.1016/J.NANO.2007.02.002
Investigations on biodistribution of technetium-99m-labeled carbohydrate-coated poly(propylene imine) dendrimers.
H. Agashe (2007)
Dendritic polymer
AK 100594–602. Patri (2002)
Polypropylene imine dendrimer mediated solubility enhancement: effect of pH and functional groups of hydrophobes.
U. Gupta (2007)
10.1016/S0168-3659(99)00140-6
Polymeric drugs based on conjugates of synthetic and natural macromolecules. II. Anti-cancer activity of antibody or (Fab')(2)-targeted conjugates and combined therapy with immunomodulators.
B. Říhová (2000)
10.1016/0304-3835(96)04407-2
Apoptosis induced by retinoic acid in Hep 3B cells in vitro.
D. Kim (1996)
10.1039/B515624F
Molecular heterogeneity analysis of poly(amidoamine) dendrimer-based mono- and multifunctional nanodevices by capillary electrophoresis.
X. Shi (2006)
10.1097/00004424-200001000-00006
Development of a tumor-targeting MR contrast agent using the high-affinity folate receptor: work in progress.
S. Konda (2000)
10.1021/JM040187V
Targeting and inhibition of cell growth by an engineered dendritic nanodevice.
T. Thomas (2005)
10.1016/J.JCONREL.2005.10.030
Induction of apoptosis in A549 human lung cancer cells by all-trans retinoic acid incorporated in DOTAP/cholesterol liposomes.
S. Kawakami (2006)
Designing dendrimers for drug
MJ 876–883.Liu (1999)
10.1182/BLOOD.V96.10.3529.H8003529_3529_3536
Differentiation-independent retinoid induction of folate receptor type beta, a potential tumor target in myeloid leukemia.
H. Wang (2000)
10.1080/10611860600825159
Intracellular macrophage uptake of rifampicin loaded mannosylated dendrimers
Palanirajan Vijayaraj Kumar (2006)
10.1002/ANIE.199001381
Starburst Dendrimers: Molecular‐Level Control of Size, Shape, Surface Chemistry, Topology, and Flexibility from Atoms to Macroscopic Matter
D. Tomalia (1990)
10.1023/A:1020398624602
Design and Function of a Dendrimer-Based Therapeutic Nanodevice Targeted to Tumor Cells Through the Folate Receptor
A. Quintana (2004)
Polypropylene imine
U Gupta (2007)
10.1016/j.ejps.2008.04.002
Targeting of efavirenz loaded tuftsin conjugated poly(propyleneimine) dendrimers to HIV infected macrophages in vitro.
T. Dutta (2008)
10.1002/ANIE.199313081
Poly(propylene imine) Dendrimers: Large‐Scale Synthesis by Hetereogeneously Catalyzed Hydrogenations
Ellen Marleen Monique De Brabander-Van Den Berg (1993)
10.1097/00004424-200204000-00005
Biodistribution of a 153Gd-Folate Dendrimer, Generation = 4, in Mice With Folate-Receptor Positive and Negative Ovarian Tumor Xenografts
S. Konda (2002)
Delivery of liposomes into cultured KB cells via folate receptor-mediated endocytosis.
R. Lee (1994)
10.1016/J.BBRC.2004.08.176
Modulation of the retinoic acid-induced cell apoptosis and differentiation by the human TR4 orphan nuclear receptor.
Y. Lee (2004)
10.1016/S0168-3659(99)00141-8
Polymeric drugs based on conjugates of synthetic and natural macromolecules. I. Synthesis and physico-chemical characterisation.
K. Ulbrich (2000)
10.1021/BM050802S
Dendrimers: novel polymeric nanoarchitectures for solubility enhancement.
U. Gupta (2006)
10.1016/J.ADDR.2005.09.014
Targeted drug delivery with dendrimers: comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion complex.
A. Patri (2005)
Modulation of the retinoic acid
YF Lee (2004)
10.1111/j.1349-7006.2001.tb01046.x
Overexpression of Retinoic Acid Receptor β Induces Growth Arrest and Apoptosis in Oral Cancer Cell Lines
K. Hayashi (2001)
Identification of OTX2 as a medulloblastoma oncogene whose product can be targeted by all-trans retinoic acid.
C. Di (2005)
10.1016/S1773-2247(05)50008-X
PEGylated peptide-based dendritic nanoparticulate systems for delivery of artemether
D. Bhadra (2005)
10.1080/17435390802105167
Toxicological investigation of surface engineered fifth generation poly (propyleneimine) dendrimers in vivo
T. Dutta (2008)
10.1016/J.BIOMATERIALS.2005.06.007
Preparation, cellular transport, and activity of polyamidoamine-based dendritic nanodevices with a high drug payload.
P. Kolhe (2006)
10.1158/0008-5472.CAN-04-3921
Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer.
J. Kukowska-Latallo (2005)
The development of a tumor targeting magnetic resonance contrast agent using the high affinity folate receptor: Work in progress
SD Konda (2000)
10.1016/S1461-5347(99)00203-5
Designing dendrimers for drug delivery.
Liu (1999)
Targeted drug
AK 6466–471. Patri (2005)
10.1007/BF02668091
Specific targeting of folate–dendrimer MRI contrast agents to the high affinity folate receptor expressed in ovarian tumor xenografts
S. Konda (2007)
10.1021/JA952725M
Peptide-Mediated Release of Folate-Targeted Liposome Contents from Endosomal Compartments1
K. Vogel (1996)
10.1002/MASY.19961010128
Starburstr̀ dendrimers — Nanoscopic supermolecules according to dendritic rules and principles
D. Tomalia (1996)
10.1016/S0378-5173(03)00132-7
A PEGylated dendritic nanoparticulate carrier of fluorouracil.
D. Bhadra (2003)
10.1002/ijc.11354
Inhibition of tumor growth by biodegradable microspheres containing all‐trans‐retinoic acid in a human head‐and‐neck cancer xenograft
Yongdoo Choi (2003)
Polymer-protein and polymer-drug conjugates in cancer therapy.
M. Thanou (2003)
10.1016/j.vaccine.2008.04.058
Poly(propyleneimine) dendrimer and dendrosome mediated genetic immunization against hepatitis B.
T. Dutta (2008)
10.1080/10611860600965914
Poly (propyleneimine) dendrimer based nanocontainers for targeting of efavirenz to human monocytes/macrophages in vitro
T. Dutta (2007)
10.1182/BLOOD.V100.2.594
Strategy for the treatment of acute myelogenous leukemia based on folate receptor beta-targeted liposomal doxorubicin combined with receptor induction using all-trans retinoic acid.
X. Q. Pan (2002)
10.1080/02652040802312572
Exploring dendrimer towards dual drug delivery: pH responsive simultaneous drug-release kinetics
Rakesh K Tekade (2009)
10.1080/17458080600647146
Dendrosome-based gene delivery
T. Dutta (2006)
Simultaneous spectrophotometric estimation of methotrexate and all-trans retinoic acid in mixture
RK Tekade (2008)
Drug Delivery Systems in Cancer Therapy
K. H. K. Kwok (2004)
10.1163/156856204322977201
Dynamics of cellular entry and drug delivery by dendritic polymers into human lung epithelial carcinoma cells
S. Kannan (2004)
10.1016/0005-2736(94)00235-H
Folate-mediated tumor cell targeting of liposome-entrapped doxorubicin in vitro.
R. Lee (1995)
10.1208/pt060367
Poly(amidoamine) (PAMAM) dendritic nanostructures for controlled sitespecific delivery of acidic anti-inflammatory active ingredient
Abhay Asthana (2008)
10.1016/S0040-4020(03)00437-X
Dendrimers as potential drug carriers; encapsulation of acidic hydrophobes within water soluble PAMAM derivatives
A. Beezer (2003)
10.1016/J.BBAGEN.2006.12.007
Targeting potential and anti-HIV activity of lamivudine loaded mannosylated poly (propyleneimine) dendrimer.
T. Dutta (2007)
10.1016/S1367-5931(02)00347-2
Dendritic polymer macromolecular carriers for drug delivery.
A. Patri (2002)
Investigation on biodistribution of technetium-99m labeled carbohydrate coated PPIdendrimers
HB Agashe (2007)
10.1002/ANIE.199316651
Book Review: The Organic Chemistry of Polycoordinated Iodine. By. A. Varvolis
P. Stang (1993)



This paper is referenced by
10.1016/j.actbio.2019.09.009
Tumor Microenvironment Targeted Nanotherapeutics for Cancer Therapy and Diagnosis: A review.
S. Thakkar (2019)
10.1039/C3TB20724B
Dendrimer-based nanodevices for targeted drug delivery applications.
J. Zhu (2013)
10.1016/j.msec.2019.110275
Advanced nanoscale carrier-based approaches to overcome biopharmaceutical issues associated with anticancer drug 'Etoposide'.
H. Choudhury (2020)
10.1021/bm501285t
Advances in combination therapies based on nanoparticles for efficacious cancer treatment: an analytical report.
S. Mignani (2015)
10.1016/J.PROGPOLYMSCI.2013.07.005
Dendrimer as nanocarrier for drug delivery
P. Kesharwani (2014)
10.1039/c9tb02528f
Bioinspired pyrimidine-containing cationic polymers as effective nanocarriers for DNA and protein delivery.
Y. Xiao (2020)
10.1021/acs.langmuir.7b00742
Elegant pH-Responsive Nanovehicle for Drug Delivery Based on Triazine Dendrimer Modified Magnetic Nanoparticles.
Amir Landarani-Isfahani (2017)
10.2217/nnm-2017-0210
Recent advances in exosome-based nanovehicles as RNA interference therapeutic carriers.
Rahul Maheshwari (2017)
10.1016/j.drudis.2016.06.029
RNAi-combined nano-chemotherapeutics to tackle resistant tumors.
Rakesh K Tekade (2016)
10.1201/B17191-12
Nanomaterial-Based Gene and Drug Delivery: Pulmonary Toxicity Considerations
Mahavir Bhupal Chougule (2014)
10.1016/B978-0-12-809717-5.00014-2
Carbon Nanotubes in Targeting and Delivery of Drugs
Rakesh K Tekade (2017)
10.1007/978-3-319-43525-1_16
Exploiting Nanocarriers for Combination Cancer Therapy
Y. W. Kong (2016)
10.2174/138945011796818135
Evaluation of dendrimer safety and efficacy through cell line studies.
P. Kesharwani (2011)
10.1039/C3NJ00300K
Dendrimers as macromolecular tools to tackle from colon to brain tumor types: a concise overview
S. Mignani (2013)
10.1039/c7cs00550d
Dendrimers in combination with natural products and analogues as anti-cancer agents.
S. Mignani (2018)
10.2174/2210303109666190401231920
Synthesis, Characterization and in vivo Evaluation of PEGylated PPI Dendrimer for Safe and Prolonged Delivery of Insulin
Ashish Kumar Parashar (2019)
10.1016/J.PROGPOLYMSCI.2013.03.003
Dendrimer space concept for innovative nanomedicine: A futuristic vision for medicinal chemistry
S. Mignani (2013)
10.1016/J.POLYMER.2014.12.051
Impact of pegylation on biopharmaceutical properties of dendrimers
S. Thakur (2015)
Extraction and RP-HPLC determination of taxol
Rakesh K Tekade (2013)
10.1016/J.SBSR.2016.08.002
Multifunctional nanoparticle developments in cancer diagnosis and treatment
S. Parvanian (2017)
10.1016/j.drudis.2020.06.027
Nanovehicles for co-delivery of anticancer agents.
M. Zeinali (2020)
10.1016/B978-0-08-101914-6.00004-1
Biopolymer-based nanocomposites for transdermal drug delivery
Rakesh K Tekade (2017)
10.1016/J.COLSURFA.2018.10.072
Fabrication of polydopamine-based layer-by-layer nanocomposites for combined pH-sensitive chemotherapy and photothermal therapy
Hongchao Ma (2019)
10.1016/B978-0-12-809717-5.00010-5
Solid Lipid Nanoparticles for Targeting and Delivery of Drugs and Genes
Rakesh K Tekade (2017)
10.1016/B978-0-08-100716-7.00027-1
Toxicity of nanostructured biomaterials
Rakesh K Tekade (2018)
10.1016/J.JDDST.2019.04.014
Smart dendrimers: Synergizing the targeting of anticancer bioactives
Vikrant Saluja (2019)
10.1039/C3RA43094D
Materials innovation for co-delivery of diverse therapeutic cargos.
Megan E Godsey (2013)
10.1016/B978-0-12-809717-5.00001-4
Nanotechnology for the Development of Nanomedicine
Rakesh K Tekade (2017)
10.5958/2231-5713.2015.00008.2
A Review- Emerging Use of Nano-Based Carriers in Diagnosis and Treatment of Cancer-Novel Approaches
Yaqub Khan (2015)
10.1016/j.jss.2012.04.008
All-trans retinoic acid preconditioning protects against liver ischemia/reperfusion injury by inhibiting the nuclear factor kappa B signaling pathway.
J. Rao (2013)
10.1016/j.drudis.2016.12.007
The use of nanoscaffolds and dendrimers in tissue engineering.
Bapi Gorain (2017)
10.1016/j.ajps.2019.08.001
Recent Advances Of Biomimetic Nano-systems in the Diagnosis and Treatment of Tumor
Anning Li (2019)
See more
Semantic Scholar Logo Some data provided by SemanticScholar