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

Hyaluronic Acid Based Self-assembling Nanosystems For CD44 Target Mediated SiRNA Delivery To Solid Tumors.

S. Ganesh, A. Iyer, D. Morrissey, M. Amiji
Published 2013 · Biology, Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
Anticancer therapeutics employing RNA interference mechanism holds promising potentials for sequence-specific silencing of target genes. However targeted delivery of siRNAs to tumor tissues and cells and more importantly, their intracellular release at sites of interest still remains a major challenge that needs to be addressed before this technique could become a clinically viable option. In the current study, we have engineered and screened a series of CD44 targeting hyaluronic acid (HA) based self-assembling nanosystems for targeted siRNA delivery. The HA polymer was functionalized with lipids of varying carbon chain lengths/nitrogen content, as well as polyamines for assessing siRNA encapsulation. From the screens, several HA-derivatives were identified that could stably encapsulate/complex siRNAs and form self-assembled nanosystems, as determined by gel retardation assays and dynamic light scattering. Many HA derivatives could transfect siRNAs into cancer cells overexpressing CD44 receptors. Interestingly, blocking the CD44 receptors on the cells using free excess soluble HA prior to incubation of cy3-labeled-siRNA loaded HA nano-assemblies resulted in >90% inhibition of the receptor mediated uptake, confirming target specificity. In addition, SSB/PLK1 siRNA encapsulated in HA-PEI/PEG nanosystems demonstrated dose dependent and target specific gene knockdown in both sensitive and resistant A549 lung cancer cells overexpressing CD44 receptors. More importantly, these siRNA encapsulated nanosystems demonstrated tumor selective uptake and target specific gene knock down in vivo in solid tumors as well as in metastatic tumors. The HA based nanosystems thus portend to be promising siRNA delivery vectors for systemic targeting of CD44 overexpressing cancers including tumor initiating (stem-) cells and metastatic lesions.
This paper references
10.1038/ncponc1066
Metastasis: a therapeutic target for cancer
P. Steeg (2008)
10.1016/J.DRUDIS.2006.07.005
Exploiting the enhanced permeability and retention effect for tumor targeting.
A. Iyer (2006)
10.1021/mp800024g
Anticancer therapeutics: targeting macromolecules and nanocarriers to hyaluronan or CD44, a hyaluronan receptor.
Virginia M Platt (2008)
10.1158/0008-5472.CAN-10-0749
Definition of ubiquitination modulator COP1 as a novel therapeutic target in human hepatocellular carcinoma.
Y-H Lee (2010)
10.1088/0957-4484/21/23/232001
RNAi nanomedicines: challenges and opportunities within the immune system.
Shiri Weinstein (2010)
10.1038/sj.gt.3302694
Prospects of RNA interference therapy for cancer
S. Pai (2006)
10.1242/dmm.000976
Mouse xenograft models vs GEM models for human cancer therapeutics
A. Richmond (2008)
A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs.
Y. Matsumura (1986)
10.1172/JCI37515
Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice.
A. Judge (2009)
10.1083/JCB.11.2.273
PREFERENTIAL STAINING OF NUCLEIC ACID-CONTAINING STRUCTURES FOR ELECTRON MICROSCOPY
H. Huxley (1961)
10.1016/j.addr.2009.04.018
siRNA delivery systems for cancer treatment.
Yu-Kyoung Oh (2009)
10.1002/bip.20978
Hyaluronic acid-polyethyleneimine conjugate for target specific intracellular delivery of siRNA.
G. Jiang (2008)
10.1016/j.jconrel.2008.04.012
Evaluation of the effect of vector architecture on DNA condensation and gene transfer efficiency.
Brenda F. Canine (2008)
10.1158/0008-5472.CAN-05-2018
Prospective identification of tumorigenic prostate cancer stem cells.
A. Collins (2005)
10.1093/NAR/29.17.3694
Development of an effective gene delivery system: a study of complexes composed of a peptide-based amphiphilic DNA compaction agent and phospholipid.
E. Murphy (2001)
10.1371/journal.pone.0010764
Inhibition of ABCB1 (MDR1) Expression by an siRNA Nanoparticulate Delivery System to Overcome Drug Resistance in Osteosarcoma
Michiro Susa (2010)
10.1517/17425240903241796
Non-viral gene delivery using nanoparticles
A. J. Ditto (2009)
10.1038/gt.2011.146
Tumor vasculature is a key determinant for the efficiency of nanoparticle-mediated siRNA delivery
L. Li (2012)
10.1016/J.JCONREL.2003.08.004
Extracellular and intracellular barriers in non-viral gene delivery.
M. Ruponen (2003)
10.1073/pnas.0610117104
Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma
M. Prince (2007)
10.1016/0003-2697(73)90169-3
A sensitive method for localization of disulfide containing peptides in column effluents.
A. Habeeb (1973)
10.1517/17425241003730399
Nanostructured hyaluronic acid-based materials for active delivery to cancer
D. Ossipov (2010)
10.2217/17435889.3.6.761
Co-delivery of siRNA and an anticancer drug for treatment of multidrug-resistant cancer.
M. Saad (2008)
10.1016/j.bmc.2011.09.024
'Click' synthesis of dextran macrostructures for combinatorial-designed self-assembled nanoparticles encapsulating diverse anticancer therapeutics.
Sampath C Abeylath (2011)
10.1166/JNN.2006.434
Receptor-mediated gene delivery into antigen presenting cells using mannosylated chitosan/DNA nanoparticles.
T. Kim (2006)
10.1007/s00253-007-0984-y
Applications of RNA interference: current state and prospects for siRNA-based strategies in vivo
A. Aigner (2007)
10.1021/MA051929C
Direct Visualization of Hyaluronic Acid Polymer Chain by Self-Assembled One-Dimensional Array of Gold Nanoparticles
H. Lee (2006)
10.1073/PNAS.79.21.6574
Evolution of tumor cell heterogeneity during progressive growth of individual lung metastases.
G. Poste (1982)
10.1093/JNCI/DJM135
Drug resistance and the solid tumor microenvironment.
O. Trédan (2007)
10.1016/J.ADDR.2007.03.005
RNAi therapeutics: principles, prospects and challenges.
L. Aagaard (2007)
10.1111/j.1742-4658.2010.07904.x
Efficient and targeted delivery of siRNA in vivo
M. Shim (2010)
10.1080/10611860802095494
An insight on hyaluronic acid in drug targeting and drug delivery.
A. Yadav (2008)
Hyaluronic acidpolyethyleneimine conjugate for target specific intracellular delivery of siRNA. Biopolymers 2008;89:635e42
G Jiang (2008)
10.1016/S1074-5521(00)80019-8
Probing the mechanism of transport and compartmentalisation of polyamines in mammalian cells.
P. Cullis (1999)
10.1002/jgm.696
Exploring polyethylenimine‐mediated DNA transfection and the proton sponge hypothesis
A. Akinc (2005)
Heterogeneity of tumor cells from a single mouse mammary tumor.
D. Dexter (1978)
10.1021/ar2000106
Combinatorial-designed multifunctional polymeric nanosystems for tumor-targeted therapeutic delivery.
Sampath C Abeylath (2011)
10.1038/nchembio839
RNAi therapeutics: a potential new class of pharmaceutical drugs
D. Bumcrot (2006)
10.1080/10611860802472461
Cationic derivatives of biocompatible hyaluronic acids for delivery of siRNA and antisense oligonucleotides
Su-Eun Han (2009)
10.1023/B:DRUG.0000026247.72656.8a
Hyaluronic-acid butyric esters as promising antineoplastic agents in human lung carcinoma: A preclinical study
D. Coradini (2004)
10.1016/j.biomaterials.2008.09.025
Biodegradable amphiphilic poly(ethylene oxide)-block-polyesters with grafted polyamines as supramolecular nanocarriers for efficient siRNA delivery.
X. Xiong (2009)
10.1016/j.biomaterials.2010.05.067
Paclitaxel-clusters coated with hyaluronan as selective tumor-targeted nanovectors.
I. Rivkin (2010)



This paper is referenced by
10.1002/jcp.26238
Novel nanohydrogel of hyaluronic acid loaded with quercetin alone and in combination with temozolomide as new therapeutic tool, CD44 targeted based, of glioblastoma multiforme
M. Barbarisi (2018)
10.1007/s12247-014-9183-4
Recent In Vivo Evidences of Particle-Based Delivery of Small-Interfering RNA (siRNA) into Solid Tumors
Y. Wen (2014)
10.1093/chromsci/bmw074
Determination of Doxorubicin in Stealth Hyalurionic Acid-Based Nanoparticles in Rat Plasma by the Liquid-Liquid Nanoparticles-Breaking Extraction Method: Application to a Pharmacokinetic Study.
Xiaopeng Han (2016)
10.1016/j.aquatox.2014.03.024
Trophic transfer potential of aluminium oxide nanoparticles using representative primary producer (Chlorella ellipsoides) and a primary consumer (Ceriodaphnia dubia).
Sunandan Pakrashi (2014)
10.1021/acs.biomac.5b00941
Hyaluronic Acid Engineered Nanomicelles Loaded with 3,4-Difluorobenzylidene Curcumin for Targeted Killing of CD44+ Stem-Like Pancreatic Cancer Cells.
P. Kesharwani (2015)
10.1016/j.biomaterials.2018.03.046
Enzyme-triggered size shrink and laser-enhanced NO release nanoparticles for deep tumor penetration and combination therapy.
C. Hu (2018)
10.1021/bm501065q
Selective in vitro anticancer effect of superparamagnetic iron oxide nanoparticles loaded in hyaluronan polymeric micelles.
D. Šmejkalová (2014)
10.1002/adma.201901081
Cancer-Targeting Nanoparticles for Combinatorial Nucleic Acid Delivery.
Hannah J Vaughan (2019)
10.1016/j.ijbiomac.2019.10.054
Diethylaminoethyl chitosan-hyaluronic acid polyelectrolyte complexes.
S. Raik (2019)
10.1007/s11095-014-1602-1
Cluster of Differentiation 44 Targeted Hyaluronic Acid Based Nanoparticles for MDR1 siRNA Delivery to Overcome Drug Resistance in Ovarian Cancer
X. Yang (2014)
10.1016/j.jconrel.2017.09.028
Nano‐delivery system targeting to cancer stem cell cluster of differentiation biomarkers
A. Mokhtarzadeh (2017)
10.1002/adbi.201800049
Receptor‐Targeted Drug Delivery and the (Many) Problems We Know of: The Case of CD44 and Hyaluronic Acid
Julio M. Rios de la Rosa (2018)
10.1016/j.ijpharm.2018.11.009
Oral siRNA delivery using dual transporting systems to efficiently treat colorectal liver metastasis
Eun-ju Hyun (2019)
10.1016/j.colsurfb.2015.09.043
Hyaluronic acid-conjugated polyamidoamine dendrimers for targeted delivery of 3,4-difluorobenzylidene curcumin to CD44 overexpressing pancreatic cancer cells.
P. Kesharwani (2015)
10.1007/978-1-0716-0319-2_7
Preparation of Hyaluronic Acid-Based Nanoparticles for Macrophage-Targeted MicroRNA Delivery and Transfection.
N. Parayath (2020)
10.1016/j.ijpharm.2014.05.027
Study on intralymphatic-targeted hyaluronic acid-modified nanoliposome: influence of formulation factors on the lymphatic targeting.
Ye Tian-tian (2014)
10.1039/C6TB02306A
Minimum hyaluronic acid (HA) modified magnetic nanocrystals with less facilitated cancer migration and drug resistance for targeting CD44 abundant cancer cells by MR imaging.
Taeksu Lee (2017)
10.1016/j.colsurfb.2017.04.008
A supramolecular nanoparticle system based on β-cyclodextrin-conjugated poly-l-lysine and hyaluronic acid for co-delivery of gene and chemotherapy agent targeting hepatocellular carcinoma.
Qingqing Xiong (2017)
10.20517/CDR.2018.02
How to overcome ATP-binding cassette drug efflux transporter-mediated drug resistance?
Ca Jaramillo Mantilla (2018)
10.1002/adtp.201900171
Oral Delivery of Multicompartment Nanomedicines for Colorectal Cancer Therapeutics: Combining Loco‐Regional Delivery with Cell‐Target Specificity
D. T. Akhter (2020)
10.1016/j.biomaterials.2014.04.096
Tumor-specific delivery of siRNA using supramolecular assembly of hyaluronic acid nanoparticles and 2b RNA-binding protein/siRNA complexes.
Kyung-mi Choi (2014)
Lipoplexes recouverts d’acide hyaluronique pour le ciblage d’ARN interférant à des cellules tumorales surexprimant le récepteur CD44
T. Nascimento (2015)
10.1016/j.colsurfb.2014.01.017
Hyaluronated nanoparticles with pH- and enzyme-responsive drug release properties.
S. Kim (2014)
10.1016/j.jconrel.2020.08.016
Nano-therapeutics for modulating the tumour microenvironment: Design, development, and clinical translation.
Siddharth Adityan (2020)
10.1002/jcp.27552
Tumor‐derived exosomal microRNAs and proteins as modulators of macrophage function
Maryam Moradi-Chaleshtori (2019)
10.3390/molecules25163620
Natural Ingredient-Based Polymeric Nanoparticles for Cancer Treatment
K. H. Wong (2020)
10.1002/ADMI.201500256
Hyaluronic Acid-Functionalized Electrospun Polyvinyl Alcohol/Polyethyleneimine Nanofibers for Cancer Cell Capture Applications
Yili Zhao (2015)
10.1080/17425247.2019.1645115
Hyaluronan-modified nanoparticles for tumor-targeting
Y. Sakurai (2019)
10.1021/mp500024p
Nanodelivery systems for nucleic acid therapeutics in drug resistant tumors.
A. Iyer (2014)
10.1021/mp5002894
Mad2 Checkpoint Gene Silencing Using Epidermal Growth Factor Receptor-Targeted Chitosan Nanoparticles in Non-Small Cell Lung Cancer Model
A. Nascimento (2014)
10.1016/j.actbio.2015.08.029
Intracellular delivery and antitumor effects of a redox-responsive polymeric paclitaxel conjugate based on hyaluronic acid.
Shaoping Yin (2015)
10.1007/s12274-020-2954-y
Collaborative assembly-mediated siRNA delivery for relieving inflammation-induced insulin resistance
S. Shen (2020)
See more
Semantic Scholar Logo Some data provided by SemanticScholar