Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Pathology & Oncology Research
Published in: Pathology & Oncology Research 4/2014

01-10-2014 | Research

Amelioration of Colorectal Cancer Using Negative Lipidoid Nanoparticles to Encapsulate siRNA Against APRIL by Enema Delivery Mode

Authors: Weifeng Ding, Guihua Wang, Keke Shao, Feng Wang, Hua Huang, Shaoqing Ju, Hui Cong, Huimin Wang

Published in: Pathology & Oncology Research | Issue 4/2014

Login to get access

Abstract

A proliferation-inducing ligand (APRIL) is a key cell proliferation-regulatory molecule and have been investigated well enough in immunity regulation and a few of immune diseases. APRIL can stimulate tumor cell growth and is up-expressed in cancer tissues, especially in CRC (colorectal cancer). However, whether inhibition of APRIL can regulate tumor-relative genes expression in vivo and subsequently ameliorate the pathological progress of CRC remains obscure. To address this question, we developed a novel negative lipidoid nanoparticles (NLNs) encapsulating small interference RNA (siRNA) for selectively silencing APRIL in the parenchyma of CRC focus in vivo, which uptake proceeded through a lipid raft endocytotic pathway. Local enema delivery of APRIL-NLNs silenced APRIL in CRC cells and animal models, and then ameliorated experimentally the progress of CRC by suppressing CRC cell proliferation, metastasis, and apoptosis-related cytokine expression and did not affect the function of liver and kidneys and not trigger the immune response of CRC models. This study reveals APRIL to be a potential anti-CRC target by in vivo experiments, and suggests that the application of similar modes of siRNA delivery may be feasible in other therapeutic settings.
Literature
1.
Siegel R, Ward E, Brawley O, Jemal A (2011) Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 61:212–236PubMedCrossRef
2.
Ding W, Wang J, Wang F, Wang G, Wu Q, Ju S, Cong H, Wang H (2013) Serum sAPRIL: a potential tumor-associated biomarker to colorectal cancer. Clin Biochem 46(15):1590–1594PubMedCrossRef
3.
Sun B, Wang H, Wang X, Huang H, Ding W, Jing R, Shi G, Zhu L (2009) A proliferation- inducing ligand: a new biomarker for Non-Small Cell Lung Cancer. Exp Lung Res 35:486–500PubMedCrossRef
4.
Wang F, Chen L, Ding W, Wang G, Wu Y, Wang J, Luo L, Cong H, Wang Y, Ju S, Shao J, Wang H (2011) Serum APRIL, a potential tumor marker in pancreatic cancer. Clin Chem Lab Med 49:1715–1719PubMedCrossRef
5.
Hahne M, Kataoka T, Schröter M, Hofmann K, Irmler M, Bodmer JL, Schneider P, Bornand T, Holler N, French LE, Sordat B, Rimoldi D, Tschopp J (1998) APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth. J Exp Med 188:1185–1190PubMedCrossRefPubMedCentral
6.
Petty RD, Samuel LM, Murray GI, MacDonald G, O’Kelly T, Loudon M, Binnie N, Aly E, McKinlay A, Wang W, Gilbert F, Semple S, Collie-Duguid ES (2009) APRIL is a novel clinical chemo-resistance biomarker in colorectal adenocarcinoma identified by gene expression profiling. BMC Cancer 11:434CrossRef
7.
Wang G, Wang F, Ding W, Wang J, Jing R, Li H, Wang X, Wang Y, Ju S, Wang H (2013) APRIL induces tumorigenesis and metastasis of colorectal cancer cells via activation of the PI3K/Akt pathway. PLoS One 8:e55298PubMedCrossRefPubMedCentral
8.
Lascano V, Zabalegui LF, Cameron K, Guadagnoli M, Jansen M, Burggraaf M, Versloot M, Rodermond H, van der Loos C, Carvalho-Pinto CE, Kalthoff H, Medema JP, Hahne M (2012) The TNF family member APRIL promotes colorectal tumorigenesis. Cell Death Differ 19:1826–1835PubMedCrossRefPubMedCentral
9.
Dillon SR, Gross JA, Ansell SM, Novak AJ (2006) An APRIL to remember: novel TNF ligands as therapeutic targets. Nat Rev Drug Discov 5:235–246PubMedCrossRef
10.
Ding W, Wang J, Sun B, Ju S, Yuan H, Wang X, Wang Y, Wang H (2009) APRIL knockdown suppresses migration and invasion of human colon carcinoma cells. Clin Biochem 42:1694–1698PubMedCrossRef
11.
Wang F, Chen L, Mao ZB, Shao JG, Tan C, Huang WD (2008) Lentivirus-mediated short hairpin RNA targeting APRIL gene suppresses growth of pancreatic cancer cells in vitro and in vivo. Oncol Rep 20:135–139PubMed
12.
Wang F, Ding W, Wang J, Jing R, Wang X, Cong H, Wang Y, Ju S, Wang H (2011) Identification of microRNA-target interaction in APRIL-knockdown colorectal cancer cells. Cancer Gene Ther 18:500–509PubMedCrossRef
13.
Akinc A, Zumbuehl A, Goldberg M, Leshchiner ES, Busini V, Hossain N, Bacallado SA, Nguyen DN, Fuller J, Alvarez R, Borodovsky A, Borland T, Constien R, de Fougerolles A, Dorkin JR, Narayanannair Jayaprakash K, Jayaraman M, John M, Koteliansky V, Manoharan M, Nechev L, Qin J, Racie T, Raitcheva D, Rajeev KG, Sah DW, Soutschek J, Toudjarska I, Vornlocher HP, Zimmermann TS, Langer R, Anderson DG (2008) A combinatorial library of lipid-like materials for delivery of RNAi therapeutics. Nat Biotechnol 26:561–569PubMedCrossRefPubMedCentral
14.
Naahidi S, Jafari M, Edalat F, Raymond K, Khademhosseini A, Chen P (2013) Biocompatibility of engineered nanoparticles for drug delivery. J Control Release 166:182–194PubMedCrossRef
15.
Rao NM (2010) Cationic lipid-mediated nucleic acid delivery: beyond being cationic. Chem Phys Lipids 163:245–252PubMedCrossRef
16.
17.
Ding W, Wang F, Zhang J, Guo Y, Ju S, Wang H (2013) A novel local anti-colorectal cancer drugs delivery system: negative lipidoid nanoparticles with passive target via a size-dependent pattern. Nanotechnology 24:375101PubMedCrossRef
18.
Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168PubMed
19.
Zhou X, Wang JL, Lu J, Song Y, Kwak KS, Jiao Q, Rosenfeld R, Chen Q, Boone T, Simonet WS, Lacey DL, Goldberg AL, Han HQ (2010) Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival. Cell 142:531–543PubMedCrossRef
20.
de Fougerolles A, Vornlocher HP, Maraganore J, Lieberman J (2007) Interfering with disease: a progress report on siRNA-based therapeutics. Nat Rev Drug Discov 6:443–453PubMedCrossRef
21.
McNamara JO 2nd, Andrechek ER, Wang Y, Viles KD, Rempel RE, Gilboa E, Sullenger BA, Giangrande PH (2006) Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat Biotechnol 24:1005–1015PubMedCrossRef
22.
Palliser D, Chowdhury D, Wang QY, Lee SJ, Bronson RT, Knipe DM, Lieberman J (2006) An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection. Nature 439:89–94PubMedCrossRef
23.
Zimmermann TS, Lee AC, Akinc A, Bramlage B, Bumcrot D, Fedoruk MN, Harborth J, Heyes JA, Jeffs LB, John M, Judge AD, Lam K, McClintock K, Nechev LV, Palmer LR, Racie T, Röhl I, Seiffert S, Shanmugam S, Sood V, Soutschek J, Toudjarska I, Wheat AJ, Yaworski E, Zedalis W, Koteliansky V, Manoharan M, Vornlocher HP, MacLachlan I (2006) RNAi-mediated gene silencing in non-human primates. Nature 441:111–114PubMedCrossRef
24.
Heidel JD, Yu Z, Liu JY, Rele SM, Liang Y, Zeidan RK, Kornbrust DJ, Davis ME (2007) Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA. Proc Natl Acad Sci U S A 104:5715–5721PubMedCrossRefPubMedCentral
25.
Howard KA, Rahbek UL, Liu X, Damgaard CK, Glud SZ, Andersen MØ, Hovgaard MB, Schmitz A, Nyengaard JR, Besenbacher F, Kjems J (2006) RNA interference in vitro and in vivo using a novel chitosan/siRNA nanoparticle system. Mol Ther 14:476–484PubMedCrossRef
26.
Kim WJ, Christensen LV, Jo S, Yockman JW, Jeong JH, Kim YH, Kim SW (2006) Cholesteryl oligoarginine delivering vascular endothelial growth factor siRNA effectively inhibits tumor growth in colon adenocarcinoma. Mol Ther 14:343–350PubMedCrossRef
27.
Peer D, Zhu P, Carman C, Lieberman J, Shimaoka M (2007) Selective gene silencing in activated leukocytes by targeting siRNAs to the integrin lymphocyte function-associated antigen-1. Proc Natl Acad Sci U S A 104:4095–4100PubMedCrossRefPubMedCentral
28.
Peer D, Park EJ, Morishita Y, Carman CV, Shimaoka M (2008) Systemic leukocyte-directed siRNA delivery revealing Cyclin D1 as an anti-inflammatory target. Science 319:627–630PubMedCrossRefPubMedCentral
29.
Jackson AL, Bartz SR, Schelter J, Kobayashi SV, Burchard J, Mao M, Li B, Cavet G, Linsley PS (2003) Expression profiling reveals off-target gene regulation by RNAi. Nat Biotechnol 21:635–637PubMedCrossRef
30.
Fedorov Y, Anderson EM, Birmingham A, Reynolds A, Karpilow J, Robinson K, Leake D, Marshall WS, Khvorova A (2006) Off-target effects by siRNA can induce toxic phenotype. RNA 12:1188–1196PubMedCrossRefPubMedCentral
31.
Judge AD, Sood V, Shaw JR, Fang D, McClintock K, MacLachlan I (2005) Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat Biotechnol 23:457–462PubMedCrossRef
32.
Takahashi N, Tamagawa K, Shimizu K, Fukui T, Maitani Y (2003) Effects on M5076-hepatic metastasis of retinoic acid and N-(4-hydroxyphenyl) retinamide, fenretinide entrapped in SG-liposomes. Biol Pharm Bull 26:1060–1063PubMedCrossRef
Metadata
Title
Amelioration of Colorectal Cancer Using Negative Lipidoid Nanoparticles to Encapsulate siRNA Against APRIL by Enema Delivery Mode
Authors
Weifeng Ding
Guihua Wang
Keke Shao
Feng Wang
Hua Huang
Shaoqing Ju
Hui Cong
Huimin Wang
Publication date
01-10-2014
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 4/2014
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-014-9779-5

Other articles of this Issue 4/2014

Pathology & Oncology Research 4/2014 Go to the issue

Research

The Predictive Value for Pulmonary Infection by Area Over the Neutrophil Curve (D-index) in Patients Who Underwent Reduced Intensity Hematopoietic Stem Cell Transplantation

Research

Oxidative DNA Damage as a Potential Early Biomarker of Helicobacter pylori Associated Carcinogenesis

Research

Frequency of Genetic and Epigenetic Alterations of p14ARF and p16INK4A in Head and Neck Cancer in a Hungarian Population

Research

Treatment of Refractory Hairy Cell Leukemia with a BRAF-inhibitor: Lessons to be Learnt

Research

Psychological Changes in Melanoma Patients During Ipilimumab Treatment Compared to Low-Dose Interferon Alpha Therapy—A Follow-Up Study of First Experiences

Research

HMGA1 Interacts with β-Catenin to Positively Regulate Wnt/β-Catenin Signaling in Colorectal Cancer Cells
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits