Back to Browse Journals » International Journal of Nanomedicine » Volume 7

Nanoparticle-based delivery of small interfering RNA: challenges for cancer therapy

Authors Miele E, Spinelli GP, Miele E, Di Fabrizio E, Ferretti E, Tomao S, Gulino A

Published Date July 2012 Volume 2012:7 Pages 3637—3657

DOI http://dx.doi.org/10.2147/IJN.S23696

Received 9 January 2012, Accepted 28 February 2012, Published 20 July 2012

Evelina Miele,1,* Gian Paolo Spinelli,2,* Ermanno Miele,3 Enzo Di Fabrizio,3,6 Elisabetta Ferretti,4 Silverio Tomao,2 Alberto Gulino,1,5

1Department of Molecular Medicine, 2Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, 3Nanostructures, Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genova, 4Department of Experimental Medicine, Sapienza University of Rome, Rome, 5Center for Life Nanoscience, Istituto Italiano di Tecnologia, Rome, Italy, 6BIONEM lab, University of Magna Graecia, Campus S. Venuta, Viale Europa 88100 Catanzaro, Italy

*These authors contributed equally to this work

Abstract: During recent decades there have been remarkable advances and profound changes in cancer therapy. Many therapeutic strategies learned at the bench, including monoclonal antibodies and small molecule inhibitors, have been used at the bedside, leading to important successes. One of the most important advances in biology has been the discovery that small interfering RNA (siRNA) is able to regulate the expression of genes, by a phenomenon known as RNA interference (RNAi). RNAi is one of the most rapidly growing fields of research in biology and therapeutics. Much research effort has gone into the application of this new discovery in the treatment of various diseases, including cancer. However, even though these molecules may have potential and strong utility, some limitations make their clinical application difficult, including delivery problems, side effects due to off-target actions, disturbance of physiological functions of the cellular machinery involved in gene silencing, and induction of the innate immune response. Many researchers have attempted to overcome these limitations and to improve the safety of potential RNAi-based therapeutics. Nanoparticles, which are nanostructured entities with tunable size, shape, and surface, as well as biological behavior, provide an ideal opportunity to modify current treatment regimens in a substantial way. These nanoparticles could be designed to surmount one or more of the barriers encountered by siRNA. Nanoparticle drug formulations afford the chance to improve drug bioavailability, exploiting superior tissue permeability, payload protection, and the “stealth” features of these entities. The main aims of this review are: to explain the siRNA mechanism with regard to potential applications in siRNA-based cancer therapy; to discuss the possible usefulness of nanoparticle-based delivery of certain molecules for overcoming present therapeutic limitations; to review the ongoing relevant clinical research with its pitfalls and promises; and to evaluate critically future perspectives and challenges in siRNA-based cancer therapy.

Keywords: small interfering RNA, nanoparticles, cancer therapy, delivery strategies, biological barriers, clinical trials

Download Article [PDF] View Full Text [HTML] 

Creative Commons License This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

Readers of this article also read:

Preparation, characterization, and in vitro osteoblast functions of a nano-hydroxyapatite/polyetheretherketone biocomposite as orthopedic implant material

Ma R, Tang SC, Tan HL, Lin WT, Wang YG, Wei J, Zhao LM, Tang TT

International Journal of Nanomedicine 2014, 9:3949-3961

Published Date: 18 August 2014

The therapeutic effects of MSc1 nanocomplex, synthesized by nanochelating technology, on experimental autoimmune encephalomyelitic C57/BL6 mice

Fakharzadeh S, Sahraian MA, Hafizi M, Kalanaky S, Masoumi Z, Mahdavi M, Kamalian N, Minagar A, Nazaran MH

International Journal of Nanomedicine 2014, 9:3841-3853

Published Date: 11 August 2014

Radiation dose to the nodal regions during prone versus supine breast irradiation

Csenki M, Újhidy D, Cserháti A, Kahán Z, Varga Z

Therapeutics and Clinical Risk Management 2014, 10:367-372

Published Date: 21 May 2014

Long-term MRI tracking of dual-labeled adipose-derived stem cells homing into mouse carotid artery injury

Qin JB, Li KA, Li XX, Xie QS, Lin JY, Ye KC, Jiang ME, Zhang GX, Lu XW

International Journal of Nanomedicine 2012, 7:5191-5203

Published Date: 2 October 2012

Towards real-time detection of tumor margins using photothermal imaging of immune-targeted gold nanoparticles

Jakobsohn K, Motiei M, Sinvani M, Popovtzer R

International Journal of Nanomedicine 2012, 7:4707-4713

Published Date: 28 August 2012

Novel micelle formulation of curcumin for enhancing antitumor activity and inhibiting colorectal cancer stem cells

Wang K, Zhang T, Liu L, Wang XL, Wu P, Chen ZG, Ni C, Zhang JS, Hu FQ, Huang J

International Journal of Nanomedicine 2012, 7:4487-4497

Published Date: 13 August 2012

Enhanced apoptosis of ovarian cancer cells via nanocarrier-mediated codelivery of siRNA and doxorubicin

Zou S, Cao N, Cheng D, Zheng R, Wang J, Zhu K, Shuai X

International Journal of Nanomedicine 2012, 7:3823-3835

Published Date: 18 July 2012

Antibiofilm surface functionalization of catheters by magnesium fluoride nanoparticles

Lellouche J, Friedman A, Lahmi R, Gedanken A, Banin E

International Journal of Nanomedicine 2012, 7:1175-1188

Published Date: 1 March 2012

Servant leadership: a case study of a Canadian health care innovator

Vanderpyl TH

Journal of Healthcare Leadership 2012, 4:9-16

Published Date: 16 February 2012