Small interfering RNA-based nanotherapeutics for treating skin-related diseases

ABSTRACTIntroduction RNA interference (RNAi) has demonstrated great potential in treating skin-related diseases, as small interfering RNA (siRNA) can efficiently silence specific genes. The design of skin delivery systems for siRNA is important to protect the nucleic acid while facilitating both skin targeting and cellular ingestion. Entrapment of siRNA into nanocarriers can accomplish these aims, contributing to improved targeting, controlled release, and increased transfection.Areas covered The siRNA-based nanotherapeutics for treating skin disorders are summarized. First, the mechanisms of RNAi are presented, followed by the introduction of challenges for skin therapy. Then, the different nanoparticle types used for siRNA skin delivery are described. Subsequently, we introduce the mechanisms of how nanoparticles enhance siRNA skin penetration. Finally, the current investigations associated with nanoparticulate siRNA application in skin disease management are reviewed.Expert opinion The potential application of nanotherapeutic RNAi allows for a novel skin application strategy. Further clinical studies are required to confirm the findings in the cell-based or animal experiments. The capability of large-scale production and reproducibility of nanoparticle products are also critical for translation to commercialization. siRNA delivery by nanocarriers should be optimized to attain cutaneous targeting without the risk of toxicity.KEYWORDS: SiRNARNAiskin deliverytopical applicationnanoparticle Article highlights RNAi-based treatment has proven to be ideal for mitigating skin diseases such as psoriasis, cutaneous malignancy, and cutaneous wounds.Nanocarriers can be vehicles to carry siRNA-based molecules into the skin.The proper design of siRNA-loaded nanoformulations is crucial to achieve the final therapeutic outcome.Nanoparticles are applied to circumvent insufficient cell uptake with the aim of releasing siRNA cargo in the cytoplasm.A fundamental role of topical nanocarriers used for siRNA-treated skin diseases is the increase in nucleic acid penetration depth and distribution in skin.Declaration of interestThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresA reviewer on this manuscript has disclosed that they are a founder of Aldena Therapeutics, a company working to deliver siRNA to the skin using a novel microneedle system. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.Additional informationFundingThe authors are grateful for the financial support from Ministry of Science and Technology of Taiwan (MOST-110-2320-B-182-011-MY3) and Chang Gung Memorial Hospital (CORPG2J0043).