MRNA Guided Intracellular Self-Assembly of DNA-Gold Nanoparticle Conjugates as a Precise Trigger to Up-Regulate Cell Apoptosis and Activate Photothermal Therapy.

Abstract

The size of nanoparticles was generally accepted to have a close relationship with the penetration and retention properties among tumor sites, which is one of the most significant issues during nanomedicine delivery. Despite the outstanding stealth property when circulating and the penetration ability in tumor tissue, small nanoparticles still have the problem of inadequate retention time. Taking advantage of the precise self-assembly of DNA-nanoparticle conjugates, we developed an intracellular assembly system to realize the change of nanoparticle size from small to large as well as activation of therapeutic function inside cancer cells. A duplex sequence of cancer-cell-specific mRNA, survivin, was selected to hybridize with complementary sequence of gold nanoparticle-DNA (AuNP-DNA) conjugates in cancer cell cytoplasm, resulting in the specific and precise formation of intracellular assemblies. Enhanced retention behavior of AuNPs inside cancer cells was shown to be achieved because of the increased nanoparticle size. Meanwhile, an up-regulation effect of cell apoptosis and an activated photothermal therapy function were also created by the formation of AuNP aggregations, and eventually contributed to a high rate of cancer cells death up to 93.33%. In contrast, it exhibited almost no toxicity toward normal cells because of the absence of survivin-induced assembly. Therefore, this mRNA guided intracellular assembly system exhibited its potential as a new precise cancer therapy strategy, and also broadened the application field of DNA-conjugated nanoparticle assembly.