Abstract
Over the past decade, non-coding RNA-based therapeutics have proven as a great potential for the development of targeted therapies for cancer and other diseases. The discovery of the critical function of microRNAs (miRNAs) has generated great excitement in developing miRNA-based therapies. The dysregulation of miRNAs contributes to the pathogenesis of various human diseases and cancers by modulating genes that are involved in critical cellular processes, including cell proliferation, differentiation, apoptosis, angiogenesis, metastasis, drug resistance, and tumorigenesis. miRNA (miRNA mimic, anti-miRNA/antagomir) and small interfering RNA (siRNA) can inhibit the expression of any cancer-related genes/mRNAs with high specificity through RNA interference (RNAi), thus representing a remarkable therapeutic tool for targeted therapies and precision medicine. siRNA and miRNA-based therapies have entered clinical trials and recently three novel siRNA-based therapeutics were approved by the Food and Drug Administration (FDA), indicating the beginning of a new era of targeted therapeutics. The successful clinical applications of miRNA and siRNA therapeutics rely on safe and effective nanodelivery strategies for targeting tumor cells or tumor microenvironment. For this purpose, promising nanodelivery/nanoparticle-based approaches have been developed using a variety of molecules for systemic administration and improved tumor targeted delivery with reduced side effects. In this review, we present an overview of RNAi-based therapeutics, the major pharmaceutical challenges, and the perspectives for the development of promising delivery systems for clinical translation. We also highlight the passive and active tumor targeting nanodelivery strategies and primarily focus on the current applications of nanoparticle-based delivery formulations for tumor targeted RNAi molecules and their recent advances in clinical trials in human cancers.
Original language | English (US) |
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Article number | 114113 |
Pages (from-to) | 114113 |
Journal | Advanced Drug Delivery Reviews |
Volume | 182 |
DOIs | |
State | Published - Mar 2022 |
Keywords
- Cancer
- Nanoparticles
- Non-coding RNAs
- miRNA
- siRNA
- RNA, Small Interfering/administration & dosage
- MicroRNAs/administration & dosage
- Humans
- Neoplasms/drug therapy
- RNAi Therapeutics/methods
- RNA, Untranslated/administration & dosage
- Nanoparticle Drug Delivery System/chemistry
- RNA Interference/physiology
ASJC Scopus subject areas
- Pharmaceutical Science