Optimizing the Size of Micellar Nanoparticles for Efficient siRNA Delivery |
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Authors: | Shi Liang Xian‐Zhu Yang Xiao‐Jiao Du Hong‐Xia Wang Hong‐Jun Li Wei‐Wei Liu Yan‐Dan Yao Yan‐Hua Zhu Yin‐Chu Ma Jun Wang Er‐Wei Song |
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Institution: | 1. Breast Tumor Center, Sun Yat‐sen Memorial Hospital, Sun Yat‐sen University, Guangzhou, P. R. China;2. Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, P. R. China;3. Department of Medical Materials and Rehabilitation Engineering, School of Medical Engineering, Hefei University of Technology, Hefei, Anhui, P. R. China;4. The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, P. R. China |
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Abstract: | Delivery of small interfering RNA (siRNA) by nanocarriers has shown promising therapeutic potential in cancer therapy. However, poor understanding of the correlation between the physicochemical properties of nanocarriers and their interactions with biological systems has significantly hindered its anticancer efficacy. Herein, in order to identify the optimal size of nanocarriers for siRNA delivery, different sized cationic micellar nanoparticles (MNPs) (40, 90, 130, and 180 nm) are developed that exhibit similar siRNA binding efficacies, shapes, surface charges, and surface chemistries (PEGylation) to ensure size is the only variable. Size‐dependent biological effects are carefully and comprehensively evaluated through both in vitro and in vivo experiments. Among these nanocarriers, the 90 nm MNPs show the optimal balance of prolonged circulation and cellular uptake by tumor cells, which result in the highest retention in tumor cells. In contrast, larger MNPs are rapidly cleared from the circulation and smaller MNPs are inefficiently taken up by tumor cells. Accordingly, 90 nm MNPs carrying polo‐like kinase 1 (Plk1)‐specific siRNA (siPlk1) show superior antitumor efficacy, indicating that 90 nm could either be the optimal size for systemic delivery of siRNA or close to it. Our findings provide valuable information for rationally designing nanocarriers for siRNA‐based cancer therapy in the future. |
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Keywords: | cancer therapy drug delivery nanocarriers siRNA size effect |
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