Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 9, Issue 37, Pages 31543-31556Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.7b09624
Keywords
nanodiamonds; siRNA; gene delivery; HPV
Funding
- Bio & Medical Technology Development Prograin of the NRF, - Korean government, MSIP [NRF-2014M3A9A9073811]
- Basic Science Research Program through the National Research Foundation of Korea (NRF), - Ministry of Science, ICT & Future Planning [NRF-2015R1C1A2A01053307]
- National Research Foundation of Korea [2014M3A9A9073811] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Nanodiamonds have been discovered as a new exogenous material source in biomedical applications. As a new potent form of nanodiamond (ND), polyamidoamine-decorated nanodiamonds (PAMAM-NDs) were prepared for E7 or E6 oncoprotein-suppressing siRNA gene delivery for high risk human papillomavirus-induced cervical cancer, such as types 16 and 18. It is critical to understand the physicochemical properties of siRNA complexes immobilized on cationic solid ND surfaces in the aspect of biomolecular structural and conformational changes, as the new inert carbon material can be extended into the application of a gene delivery vector. A spectral study of siRNA/PAMAM-ND complexes using differential scanning calorimetry and circular dichroism spectroscopy proved that the hydrogen bonding and electrostatic interactions between siRNA and PAMAM-NDs decreased endothermic heat capacity. Moreover, siRNA/PAMAM-ND complexes showed low cell cytotoxicityand significant suppressing effects for forward target E6 and E7 oncogenic genes, proving functional and therapeutic efficacy. The cellular uptake of siRNA/PAMAM-ND complexes at 8 h was visualized by macropinocytes and direct endosomal escape of the siRNA/PAMAM-ND complexes. It is presumed that PAMAM-NDs provided a buffering cushion to adjust the pH and hard mechanical stress to escape endosomes. siRNA/PAMAM-ND complexes provide a potential organic/inorganic hybrid material source for gene delivery carriers.
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