Abstract
BackgroundGene and chemical therapy has become one of the rising stars in the field of molecular medicine during the last two decades. However, there are still numerous challenges in the development of efficient, targeted, and safe delivery systems that can avoid siRNA degradation and reduce the toxicity and adverse effects of chemotherapy medicine.ResultsIn this paper, a highly efficient AS1411 aptamer modified, dsDNA and MMP-2 cleavable peptide-fabricated gold nanocage vehicle, which could load doxorubicin hydrochloride (DOX) and siRNAs to achieve a combination of tumor responsive genetic therapy, chemotherapy, and photothermal treatment is presented. Our results show that this combined treatment achieved targeted gene silencing and tumor inhibition. After nearly one month of treatment with DOX-loaded Au-siRNA-PAA-AS1411 nanoparticles with one dose every three days in mice, a synergistic effect promoting the eradication of long-lived tumors was observed along with an increased survival rate of mice. The combined genetic, chemotherapeutic, and photothermal treatment group exhibited more than 90% tumor inhibition ratio (tumor signal) and a ~ 67% survival rate compared with a 30% tumor inhibition ratio and a 0% survival rate in the passive genetic treatment group.ConclusionsThe development of nanocarriers with double-stranded DNA and MMP-2 cleavable peptides provides a new strategy for the combined delivery of gene and chemotherapy medicine. Au-siRNA-PAA-AS1411 exerts high anticancer activities on lung cancer, indicating immense potentials for clinical application.
Highlights
Gene and chemical therapy has become one of the rising stars in the field of molecular medicine during the last two decades
The Au nanoparticles were first modified with thiolated-DNA-2 and thiolated anti-vascular endothelial growth factor (VEGF) small interfering RNA (siRNA) through Au-S bonds (DNA-2 : siRNA = 1:10 molar ratio), reacted with equal molar ratios of modified Polyacrylic acid (PAA)-1 and PAA-2
The results showed that the Au-siRNA-PAA-AS1411 gold nanocages could target the lung tumor, and they exhibited a long retention time
Summary
Gene and chemical therapy has become one of the rising stars in the field of molecular medicine during the last two decades. Gene therapy is an efficient and promising approach to treating malignant tumors by either degrading mRNAs or inhibiting their translation. Increasing attention has been focused on gene therapy due to its potential use in treating a variety of diseases, including cancers, by delivering genetic drugs to the target tumor sites [2,3,4]. The development of VEGF-targeted genetic drugs, including VEGF-A receptors, small molecule tyrosine kinase inhibitors and antibodies, has been widely investigated, and these drugs have been confirmed to be efficient anti-angiogenesis therapies [10,11,12]. A suitable gene delivery system that can protect nucleic acids from degradation and selectively deliver a sufficient amount of siRNAs to target sites is needed
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