Introduction MicroRNA-155 (miR-155) is an oncogenic microRNA, which is upregulated in

Introduction MicroRNA-155 (miR-155) is an oncogenic microRNA, which is upregulated in many human cancers including colorectal cancer (CRC). in both in vivo and in vitro experiments. Furthermore, inhibition of miR-155 by MSNs-anti-miR-155@PDA-Apt can enhance the sensitivity of SW480 to 5-fluorouracil chemotherapy. Conclusion Thus, our results suggested that MSNs-anti-miR-155@PDA-Apt is a promising nanoformulation for CRC treatment. strong class=”kwd-title” Keywords: miR-155, mesoporous silica nanoparticles, AS1411 aptamer, NF-B, 5-fluorouracil Introduction MicroRNAs (miRNAs) are a class of small (18C25 nucleotides) endogenous noncoding RNAs that can regulate gene expressions at the posttranscriptional level.1,2 The aberrant expressions of miRNAs have been became connected with tumor onset, development, and metastasis.3 Unlike brief interfering RNAs (siRNAs) with one particular focus on mRNA, miRNAs can perform gene-silencing impact by regulating buy Bosutinib multiple mRNAs, which will make them efficient equipment for the treating complex multigenic Mouse monoclonal to CTNNB1 illnesses including malignancies.4 Restoring miRNA function with miRNA mimics and inhibiting the function of the miRNA with antisense miRNA oligonucleotides (anti-miRs) will be the two main ways of modulate the experience of miRNA.5 Currently, many miRNA-based therapeutics are within the preclinical stage,6 and many miRNA-based drugs have previously moved into clinical trials for the treating cancer and Hepatitis C virus (HCV) infection.7C10 However, secure and efficient delivery of anti-miRs or miRNA mimics towards the tissue appealing remains a primary concern for the clinical applications of miRNA-based therapeutics.11 MicroRNA-155 (miR-155) is among the most salient oncogenic microRNA (oncomiR), that is upregulated in lots of human malignancies.12 Overexpression of miR-155 continues to be found to modify several cancer-related pathways involved with cell development, invasion, migration, stemness, and angiogenesis.13 Furthermore, overexpressed oncogenic miR-155 can be correlated with medicine resistance and genome instability also.14 Nuclear factor kappa B (NF-B) can be an important transcription factor that regulates the expression of target genes involved with cell growth, apoptosis, angiogenesis, immune system and inflammatory response15 and takes on a significant part along the way of tumor development and advancement.16 Previous research have shown that there surely is a confident feedback loop between NF-B and miR-155; consequently, targeting miR-155 could be an effective technique for the treating colorectal tumor (CRC).17,18 Many reports have demonstrated the potency of anti-miR-155 in the treating various miR-155-overexpressing tumors, including lymphoma,19,20 liver,21 lung,14 and breasts cancers.12 Recently, analysts possess explored many viral and nonviral vectors to provide miRNA anti-miRs or mimics to the prospective cells. Among these vectors, mesoporous silica nanoparticles (MSNs) have already been regarded as promising candidates because of the unique features, including tunable pore framework, huge surface and pore quantity, favorable biocompatibility, thermal stability, and easy surface modification.22C25 A series of stimuli-responsive gatekeepers have been developed for the controlled release of drugs from MSNs.26,27 Among them, polymerized dopamine (PDA), formed by the catechol group of dopamine in weak alkaline conditions (pH 8.5), can spontaneously bind to any material surface through covalent and noncovalent interactions.28,29 The PDA film on the surface of MSNs, which serves as a pH-sensitive gatekeeper to controlled release of drug in the acid environment of tumor, can also react with buy Bosutinib amine- or thiol-terminated active targeting ligands, such as SH-aptamer.30 AS1411 aptamer, the first US Food and Drug Administration-approved aptamer, can specifically bind to nucleolin, which is overexpressed on the cell surface of many tumors including CRC.31C35 In the present study, we explored the expression of miR-155 and NF-B in CRC tissues and cell lines and the possible relationship between miR-155 and NF-B. We further report anti-miR-155-loaded MSNs modified with polydopamine (PDA) and AS1411 aptamer (MSNs-anti-miR-155@PDA-Apt) for the targeted treatment of CRC (as shown buy Bosutinib in Scheme 1). Furthermore, we evaluate whether the inhibition of miR-155 by MSNs-anti-miR-155@PDA-Apt can enhance buy Bosutinib the sensitivity of SW480 to 5-FU chemotherapy. Open in a separate window Scheme 1 Schematic illustration of anti-miR-155-loaded MSNs-anti-miR-155@PDA-Apt nanoparticles for targeted therapy of colorectal cancer. Abbreviations: MSNs, mesoporous silica nanoparticles; PDA, polymerized dopamine; Apt, aptamer; NF-B, nuclear factor kappa B; miR-155, MicroRNA-155; P-gp, p-glycoprotein. Materials and methods Materials Cetyltrimethylammonium bromide (CTAB), tetraethyl buy Bosutinib orthosilicate (TEOS), 2-(3,4-dihydroxyphenyl) ethylamine (dopamine) hydrochloride, near infrared heptamethine cyanine.