Background: Despite therapeutics based on siRNA have an immense potential for the treatment
of incurable diseases such as cancers. However, the in vivo utilization of siRNA and also the delivery
of this agent to the target site is one of the most controversial challenges. The helpful assistance
by nanoparticles can improve stable delivery and also enhance efficacy. More nanoparticle-based
siRNA therapeutics is expected to become available in the near future.
Methods: The search strategy followed the guidelines of the Centre of Reviews and Dissemination. The studies
were identified from seven databases (Scopus, Web of Science, Academic Search Premiere, CINAHL,
Medline Ovid, Eric and Cochrane Library). Studies was selected based on titles, abstracts and full texts.
Results: One hundred twenty nine papers were included in the review. These papers defined hurdles in
RNAi delivery and also strategies to overcome these hurdles. This review discussed the existing hurdles
for systemic administration of siRNA as therapeutic agents and highlights the various strategies to overcome
these hurdles, including lipid-based nanoparticles and polymeric nanoparticles, and we also
briefly reviewed chemical modification.
Conclusion: Delivery of siRNA to the target site is the biggest challenge for its application in the clinic.
The findings of this review confirmed by encapsulation siRNA in the nanoparticles can overcome these
challenges. The rapid progress in nanotechnology has enabled the development of effective nanoparticles
as the carrier for siRNA delivery. However, our data about siRNA-based therapeutics and also
nanomedicine are still limited. More clinical data needs to be completely understood in the benefits and
drawbacks of siRNA-based therapeutics. Prospective studies must pay attention to the in vivo safety
profiles of the different delivery systems, including uninvited immune system stimulation and cytotoxicity.
In essence, the development of nontoxic, biocompatible, and biodegradable delivery systems for
medical application of RNAi-based therapeutics is needed.