Cancer is the greatest challenge in human healthcare today. Cancer causes 7.6 million deaths and economic losses of around 1 trillion dollars every year. Early diagnosis and effective treatment of cancer are crucial for saving lives. Driven by these needs, we report the development of a multifunctional plasmonic shell–magnetic core nanotechnology-driven approach for the targeted diagnosis, isolation, and photothermal destruction of cancer cells. Experimental data show that aptamer-conjugated plasmonic/magnetic nanoparticles can be used for targeted imaging and magnetic separation of a particular kind of cell from a mixture of different cancer cells. A targeted photothermal experiment using 670-nm light at 2.5 W/cm2 for 10 minutes resulted selective irreparable cellular damage to most of the cancer cells. We also showed that the aptamer-conjugated magnetic/plasmonic nanoparticle-based photothermal destruction of cancer cells is highly selective. We discuss the possible mechanism and operating principle for the targeted imaging, separation, and photothermal destruction using magnetic/plasmonic nanotechnology.
Dithiothreitol (DTT)-based displacement is widely utilized for separating ligands from their gold nanoparticle (AuNP) conjugates, a critical step for differentiating and quantifying surface-bound functional ligands and therefore the effective surface density of these species on nanoparticle-based therapeutics and other functional constructs. The underlying assumption is that DTT is smaller and much more reactive toward gold compared with most ligands of interest, and as a result will reactively displace the ligands from surface sites thereby enabling their quantification. In this study, we use complementary dimensional and spectroscopic methods to characterize the efficiency of DTT displacement. Thiolated methoxypolyethylene glycol (SH-PEG) and bovine serum albumin (BSA) were chosen as representative ligands. Results clearly show that (1) DTT does not completely displace bound SH-PEG or BSA from AuNPs, and (2) the displacement efficiency is dependent on the binding affinity between the ligands and the AuNP surface. Additionally, the displacement efficiency for conjugated SH-PEG is moderately dependent on the molecular mass (yielding efficiencies ranging from 60 to 80% measured by ATR-FTIR and ≈90% by ES-DMA), indicating that the displacement efficiency for SH-PEG is predominantly determined by the S-Au bond. BSA is particularly difficult to displace with DTT (i.e., the displacement efficiency is nearly zero) when it is in the so-called normal form. The displacement efficiency for BSA improves to 80% when it undergoes a conformational change to the expanded form through a process of pH change or treatment with a surfactant. An analysis of the three-component system (SH-PEG + BSA + AuNP) indicates that the presence of SH-PEG decreases the displacement efficiency for BSA, whereas the displacement efficiency for SH-PEG is less impacted by the presence of BSA.
The known activities of NSC109268 as proteasome or phosphatase inhibitor could explain the phenotype of S-phase delay by assuming a higher initial DNA damage load, inhibition of DNA translesion synthesis or extended checkpoint arrest.
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