Aptamer-assisted superparamagnetic iron oxide nanoparticles as multifunctional drug delivery platform for chemo-photodynamic combination therapy

Superparamagnetic iron oxide nanoparticles (SPION) were widely employed as targeted drug delivery platform due to their unique magnetic property and effortless surface modification. However, the lack of targeting accuracy has been a big obstacle for SPION used in precise medicine. Herein, the tumor-targeting of SPION was enhanced by the conjugation of an aptamer-hybridized nucleic acid structure. The aptamer modified on the surface of SPION was composed of a double-stranded DNA (dsDNA) and a G-quadruplex DNA (AS1411) structure, which carried a chemical anticancer drug, daunomycin (DNM) and a photosensitizer molecule, namely 5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin (TMPyP), respectively. The aptamer-dsDNA conjugated SPION nanocarriers (named Apt-S8@SPION) exhibited good stability in serum and nuclease DNase I. The drug-loaded nanocarriers (TMPyP&DNM&Apt-S8@SPION) have high cellular cytotoxicity to A549 and C26 cells which are represently nucleolin-overexpressing cancer cells. The nucleolin-blocking experiments unambiguously evidenced that the formed nanomedicine could target to the cell surface via the specific AS1411-nucleolin interaction, which increased the efficiency of cell uptake. Meanwhile, the TMPyP&DNM&Apt-S8@SPION nanospheres could produce cytotoxic reactive oxygen species efficiently by irradiation of visible light for establishing a new type of PDT to cancer cells. Therefore, the designed TMPyP&DNM&Apt-S8@SPION nanoparticles have magnetic-aptamer dual targeting and combined chemo-photodynamic therapy, and thus were supposed to be ideal drug delivery vehicles with great potential in the era of precision medicine.