Abstract
As a widely used anticancer drug, doxorubicin (DOX) could induce cell death mainly via interfering with DNA activity; thus, DOX could perform therapeutic effects mainly in the cell nucleus. However, most of the reported drug delivery systems lacked the well localization in the nucleus and released DOX molecules into the cytoplasm. Due to formidable barriers formed in the nuclear envelope, only around 1% of DOX could reach the nucleus and keep active. Therefore, DOX molecules were inevitably overloaded to achieve the desired therapeutic efficacy, which would induce serious side effects. Herein, we developed a highly localized drug nanocarrier for in situ release of DOX molecules to their action site where they could directly interfere with the DNA activity. In this work, we used cationic polymer-modified upconversion nanoparticles (UCNPs) as the luminescence core and gene carrier, while aptamers served as the DNA nanotrain to load DOX. Finally, the prepared nanotheranostic agent displayed good targetability, high cell apoptosis ratio (93.04%) with quite lower concentration than the LC50 of DOX, and obvious inhibition on tumor growth.
Highlights
Nowadays, cancer has been a major human health problem great progress was made in its diagnosis and treatment (Skrott et al, 2017; Wu et al, 2019)
The obtained upconversion nanoparticles (UCNPs)@PDL nanoprobe would carry DNA nanotrains to selectively target cancer cells and locate in the nucleus where the anti-proliferating cell nuclear antigen (PCNA) aptamer would specially bind with PCNA to induce the in situ release of DOX molecules
The cationic polymer, PDL, was uniformly coated onto the surface of bared UCNPs proved by zeta-potential analysis
Summary
Cancer has been a major human health problem great progress was made in its diagnosis and treatment (Skrott et al, 2017; Wu et al, 2019). The obtained UCNPs@PDL nanoprobe would carry DNA nanotrains to selectively target cancer cells and locate in the nucleus where the anti-PCNA aptamer would specially bind with PCNA to induce the in situ release of DOX molecules. The constructed UCNPs@PDL@dsDNA/DOX nanotheranostic agent could fully perform the synergistic effect of anti-PCNA aptamer and DOX molecules and achieve the targeted location therapy to obtain satisfactory therapeutic efficacy. 8.0 mL Y(oleate) solution was followed, added, and SCHEME 1 | Procedure of the designed UCNPs@PDL@dsDNA/DOX nanotheranostic agent as the highly localized drug-delivery system. The prepared UCNPs@PDL@dsDNA/DOX nanoprobe (90 μg/mL) was added and cells were incubated for different times. The mouse was sacrificed to obtain the tumor section and main organs which were sliced for hematoxylin and eosin (H&E) staining, PCNA staining, and Ki67 staining
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