Abstract
Rare Earth up-conversion nanoparticles NaYF4:20%Yb,2%Er@PEI (UCNPs) were generated via a one-step hydrothermal technique at relatively reduced temperatures. Photosensitizer Ce6 and anti-EpCAM, a highly expressed monoclonal antibody in cancer stem cells of hepatocellular carcinoma, were linked to UCNP surfaces via the formation of amide linkage between carboxyl from Ce6 or anti-EpCAM and abundant amino from PEI, leading to the formation of Ps-Ce6 and anti-EpCAM-UCNPs-Ce6 nanoparticles. The synthesized nanoparticles characterized by XRD, TEM, and IR, and their zeta potential, ROS generation ability, Ce6 loading rate, and up-conversion fluorescence properties were investigated. It has been revealed that all the products were uniformly dispersed nanoparticles (25–32 nm), which crystallized primarily as hexagonal structures, and their up-conversion fluorescence spectra were similar to that of NaYF4:20%Yb,2%Er. The Ce6 loading rate in the anti-EpCAM-UCNPs-Ce6 nanoparticles was about 2.9%, thereby resulting in good ROS generation ability. For anti-EpCAM-UCNPs-Ce6, the biosafety, targeting effect, and PDT effect exposed under near-infrared (NIR) laser (980 nm) were evaluated using human liver cancer cells (BEL-7404). The results showed that it has good biocompatibility and biosafety as well as high targeting and PDT treatment efficiencies, which renders it a potential experimental material for the near-infrared PDT study.
Highlights
As one of the most common malignant tumors globally, morbidity and mortality rates for hepatic tumors rank 6th and 4th, respectively, from all clinically observed tumor models [1]
If the anti-epithelial cell adhesion molecule (EpCAM) and photosensitizer are assembled on the surface of UCNPs via chemical reactions, it would presumably result in a good NIR-photodynamic therapy (PDT) method with high targeting ability and low side effects for hepatocellular carcinoma. ere are a few reports on the conjugation of specific antibodies with UCNPs; most of them were coated with mesoporous silica
Due to the abundance of positive charges on the surface of PEI, UCNPs treated with PEI have a rather high zeta potential. e zeta potentials of chlorin e6 (Ce6) and anti-EpCAM were reduced to 17.5 mV and 10.2 mV, respectively, when they chemically bound to the amino groups on the PEI surface, substantially reducing the damage caused by positive charges on cell membranes. e modest amount of positive charge on the surface of nanoparticles, on the other hand, prevents nanoparticle aggregation and allows them to penetrate cells
Summary
As one of the most common malignant tumors globally, morbidity and mortality rates for hepatic tumors rank 6th and 4th, respectively, from all clinically observed tumor models [1]. E up-conversion nanoparticles (UCNPs) suitable for biological application can be synthesized with many chemical methods together with further surface functional modification by photosensitizers, hydrophilic groups, targeting agent, specific antibodies, and so on, to facilitate the PDT for deep-tissue cancers, improving selectivity and biocompatibility and reducing side effects [19–21]. If some specific molecules are conjugated onto the surface of UCNPs, such as the monoclonal antibody anti-EpCAM, which can target the surface marker epithelial cell adhesion molecule (EpCAM) of the cancer stem cells of hepatocellular carcinoma, the nanosystem would possess an active targeting effect. If the anti-EpCAM and photosensitizer are assembled on the surface of UCNPs via chemical reactions, it would presumably result in a good NIR-PDT method with high targeting ability and low side effects for hepatocellular carcinoma. After binding with EpCAMexpressing hepatoma cells, PDT could be achieved after irradiation at 980 nm
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