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Published on: February 1, 2019
Delivery of therapeutic oligonucleotides in nanoscale
Lei Wu1, Wenhui Zhou2,3, Lihua Lin1
1School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, 510006, Guangdong, China.
Abstract:
Therapeutic oligonucleotides (TOs) represent one of the most promising drug candidates in the targeted cancer treatment due to their high specificity and capability of modulating cellular pathways that are not readily druggable. However, efficiently delivering of TOs to cancer cellular targets is still the biggest challenge in promoting their clinical translations. Emerging as a significant drug delivery vector, nanoparticles (NPs) can not only protect TOs from nuclease degradation and enhance their tumor accumulation, but also can improve the cell uptake efficiency of TOs as well as the following endosomal escape to increase the therapeutic index. Furthermore, targeted and on-demand drug release of TOs can also be approached to minimize the risk of toxicity towards normal tissues using stimuli-responsive NPs. In the past decades, remarkable progresses have been made on the TOs delivery based on various NPs with specific purposes. In this review, we will first give a brief introduction on the basis of TOs as well as the action mechanisms of several typical TOs, and then describe the obstacles that prevent the clinical translation of TOs, followed by a comprehensive overview of the recent progresses on TOs delivery based on several various types of nanocarriers containing lipid-based nanoparticles, polymeric nanoparticles, gold nanoparticles, porous nanoparticles, DNA/RNA nanoassembly, extracellular vesicles, and imaging-guided drug delivery nanoparticles.
Insights
Therapeutic oligonucleotides (TOs) show promise for cancer treatment. Nanoparticles enhance TO delivery, overcoming challenges for improved clinical translation and reduced toxicity.
Area of Science:
- Oncology
- Nanomedicine
- Drug Delivery
Background:
- Therapeutic oligonucleotides (TOs) offer high specificity for targeting difficult cellular pathways in cancer.
- Efficient delivery of TOs remains a significant hurdle for their clinical application.
- Nanoparticles (NPs) are emerging as key vectors for TO delivery, protecting them and enhancing tumor accumulation.
Purpose of the Study:
- To review the progress and challenges in delivering therapeutic oligonucleotides (TOs) for cancer treatment.
- To provide a comprehensive overview of various nanoparticle (NP) delivery systems for TOs.
- To discuss strategies for overcoming obstacles in the clinical translation of TO-based therapies.
Main Methods:
- Review of recent advancements in nanoparticle-based delivery of therapeutic oligonucleotides.
- Analysis of different nanocarrier types, including lipid-based, polymeric, gold, and porous nanoparticles.
- Discussion of extracellular vesicles and imaging-guided delivery systems for TOs.
Main Results:
- Nanoparticles improve TO stability, tumor targeting, cellular uptake, and endosomal escape.
- Stimuli-responsive NPs enable targeted and on-demand TO release, minimizing off-target toxicity.
- Diverse nanocarrier platforms show significant progress in enhancing TO therapeutic efficacy.
Conclusions:
- Nanoparticle-mediated delivery is crucial for overcoming the challenges associated with therapeutic oligonucleotide clinical translation.
- Continued research into various nanocarrier systems will further optimize TO efficacy and safety in cancer therapy.
- Advanced delivery strategies promise to unlock the full potential of TOs in precision oncology.
