Journal
NANOSCALE
Volume 12, Issue 45, Pages 22945-22951Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0nr05652a
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Funding
- KIST
- Pioneer Research Center Program [2014M3C1A3054141]
- National Research Foundation (NRF) of Korea - Korean government (MSIT) [2020R1A2C2008213]
- Bio & Medical Technology Development Program of the NRF - MSIT [2020M3E5E2037598]
- National Research Foundation of Korea [2E30350, 2020M3E5E2037598, 2020R1A2C2008213] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Aptamer-drug conjugates (ApDCs) are promising anticancer therapeutics with cancer cell specificity. However, versatile in vivo applications of ApDCs are hampered by their limited serum stability and inability to reach the tumour upon systemic administration. Here, we describe DNA nanoparticles of ApDCs as a platform for tumour-targeted systemic delivery of ApDCs. DNA nanoparticles of approximately 75 nm size were fabricated by self-assembly of a polymerised floxuridine (FUdR)-incorporated AS1411 aptamer produced via rolling circle amplification. The DNA nanoparticles of ApDCs showed highly efficient cancer cell uptake, enhanced serum stability, and tumour-targeted accumulation. These properties could be successfully utilised for tumour-specific apoptotic damage by ApDCs, leading to significant suppression of tumour growth without considerable systemic toxicity. Molecular analysis revealed that the enhanced anticancer potency was due to the synergic effect induced by the simultaneous activation of p53 by AS1411 and the inhibition of thymidylate synthase by FUdR, respectively, both of which were generated from the DNA nanoparticles. We therefore expect that the DNA nanoparticles of ApDCs can be a promising platform for tumour-targeted delivery of various nucleoside-incorporated ApDCs to treat cancer.
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