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Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery
Published on: May 2, 2019
Inorganic nanocarriers for siRNA delivery for cancer treatments
Ganeshlenin Kandasamy1, Dipak Maity2
1Department of Biomedical Engineering, School of Electrical and Communication, Vel Tech Rangarajan Dr. Sagunthala R&D Institute of Science and Technology, Avadi, Chennai, India.
Abstract:
RNA interference is one of the emerging methodologies utilized in the treatment of a wide variety of diseases including cancer. This method specifically uses therapeutic RNAs (TpRNAs) like small interfering RNAs (siRNAs) to regulate/silence the cancer-linked genes, thereby minimizing the distinct activities of the cancer cells while aiding in their apoptosis. But, many complications arise during the transport/delivery of these TpRNAs that include poor systemic circulation, instability/degradation inside the body environment, no targeting capacity and also low cellular internalization. These difficulties can be overcome by using nanocarriers to deliver the TpRNAs inside the cancer cells. The following are the various categories of nanocarriers-viral vectors (e.g. lentivirus and adenovirus) and non-viral nanocarriers (self-assembling nanocarriers and inorganic nanocarriers). Viral vectors suffer from disadvantages like high immunogenicity compared to the non-viral nanocarriers. Among non-viral nanocarriers, inorganic nanocarriers gained significant attention as their inherent properties (like magnetic properties) can aid in the effective cellular delivery of the TpRNAs. Most of the prior reports have discussed about the delivery of TpRNAs through self-assembling nanocarriers; however very few have reviewed about their delivery using the inorganic nanoparticles. Therefore, in this review, we have mainly focussed on the delivery of TpRNAs-i.e. siRNA, especially programmed death ligand-1 (PD-L1), survivin, B-cell lymphoma-2 (Bcl-2), vascular endothelial growth factor and other siRNAs using the inorganic nanoparticles-mainly magnetic, metal and silica nanoparticles. Moreover, we have also discussed about the combined delivery of these TpRNAs along with chemotherapeutic drugs (mainly doxorubicin) andin vitroandin vivotherapeutic effectiveness.
Insights
Inorganic nanoparticles offer a promising solution for delivering therapeutic RNAs (TpRNAs) like siRNAs to cancer cells, overcoming common delivery challenges for improved cancer treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapeutics
Background:
- RNA interference (RNAi) uses therapeutic RNAs (TpRNAs), such as small interfering RNAs (siRNAs), to silence cancer-driving genes.
- Effective delivery of TpRNAs is hindered by poor circulation, instability, lack of targeting, and low cellular uptake.
- Nanocarriers, particularly inorganic nanoparticles, show potential to overcome these delivery challenges.
Purpose of the Study:
- To review the use of inorganic nanoparticles for the delivery of TpRNAs, focusing on siRNAs targeting cancer-related genes.
- To highlight the advantages of inorganic nanocarriers over viral vectors and self-assembling nanocarriers.
- To discuss the combined delivery of TpRNAs with chemotherapeutic agents and their therapeutic efficacy.
Main Methods:
- Review of literature on inorganic nanoparticles (magnetic, metal, silica) for TpRNA delivery.
- Focus on siRNA delivery for genes like PD-L1, survivin, Bcl-2, and VEGF.
- Analysis of combined TpRNA and doxorubicin delivery strategies.
Main Results:
- Inorganic nanoparticles enhance systemic circulation, stability, targeting, and cellular internalization of TpRNAs.
- Magnetic nanoparticles offer unique properties for guided cellular delivery.
- Combined delivery of TpRNAs and doxorubicin demonstrates synergistic therapeutic effects.
Conclusions:
- Inorganic nanoparticles represent a superior platform for siRNA delivery in cancer therapy.
- Targeted delivery and combination therapies using inorganic nanocarriers hold significant promise for cancer treatment.
- Further research into inorganic nanoparticle-mediated RNAi is crucial for clinical translation.
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