Nanocarrier mediated delivery of siRNA/miRNA in combination with chemotherapeutic agents for cancer therapy: Current progress and advances

Abstract

Chemotherapeutic agents have certain limitations when it comes to treating cancer, the most important being severe side effects along with multidrug resistance developed against them. Tumor cells exhibits drug resistance due to activation of various cellular level processes viz. activation of drug efflux pumps, anti-apoptotic defense mechanisms etc. Currently, RNA interference (RNAi) based therapeutic approaches are under vibrant scrutinization to seek cancer cure. Especially small interfering RNA (siRNA) and micro RNA (miRNA), are able to knock down the carcinogenic genes by targeting the mRNA expression, which underlies the uniqueness of this therapeutic approach. Recent research focus in the regime of cancer therapy involves the engagement of targeted delivery of siRNA/miRNA in combinations with other therapeutic agents (such as gene, DNA or chemotherapeutic drug) for targeting permeability glycoprotein (P-gp), Multidrug resistant protein 1(MRP-1), B-cell lymphoma (BCL-2) and other targets that are mainly responsible for resistance in cancer therapy. RNAi-chemotherapeutic drug combinations have also been found to be effective against different molecular targets as well and can increase the sensitization of cancer cells to therapy several folds. However, due to stability issues associated with siRNA/miRNA suitable protective carrier is needed and nanotechnology based approaches have been widely explored to overcome these drawbacks. Furthermore, it has been univocally advocated that the co-delivery of siRNA/miRNA with other chemodrugs significantly enhances their capability to overcome cancer resistance compared to naked counterparts. The objective of this article is to review recent nanocarrier based approaches adopted for the delivery of siRNA/miRNA combinations with other anticancer agents (siRNA/miRNA/pDNA/chemodrugs) to treat cancer.

Regulatory role of microRNA184 in osteosarcoma cells

“…MicroRNAs (miRNAs), which widely exist in animals and plants, are non-coding, small, regulatory RNAs (Orang and Barzegari, 2014;Saadatian et al, 2014) that can negatively regulate gene expression. They function via complete or incomplete pairing with target genes, or by inhibiting the downstream transcription of target proteins, mRNA degradation, and protein translation (Gandhi et al, 2014). MiRNAs have numerous functions, affecting growth, metabolism, the endocrine system, hormone secretion, and embryonic stem cells, thereby regulating adaption to the environment.…”

RNAi-based Cancer Therapeutics: Are we there yet?

“…In the last decade or so, the RNA interference (RNAi) technology, mediated primarily by small interfering RNA (siRNAs) and micro RNA (miRNAs) has emerged as one of the most promising strategies for cancer therapeutics [6][7][8], primarily due to its high specificity, precise mechanism of action and potency [9]. The strategy is also advantageous in terms of its capability to target multiple oncogenes simultaneously.…”

Which one performs better for targeted lung cancer combination therapy: pre- or post-bombesin-decorated nanostructured lipid carriers?

“…(Gandhi et al, 2014;Tsouris et al, 2014). The efficacy of DOX, encapsulated in PEGylated liposome (Caelyx/Doxil), has been demonstrated by a number of authoritative clinical studies from preclinical studies to phase II studies (Yang et al, 2011).…”