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  • AuNP RGD was also analyzed by mixing the

    2022-04-29

     AuNP-RGD was also analyzed by mixing the nanoparticles in PBS me-dium and determining the hydrodynamic diameters by DLS measure-ments over a period of 7 days (Fig. 3C). The synthesized nanoparticles displayed near constant hydrodynamic diameters over this period of time, establishing its high colloidal stability in physiological conditions. These results further corroborated the findings of highly negative zeta potential of AuNP-RGD in aqueous medium.
    It is pertinent to mention here that in the past, several strate-gies have been reported for synthesis of functionalized Au nano-particles with better shape and size control [1,11,13,28,29]. The objective of the present work was to develop a simple and effi-cient approach for synthesis of clinically relevant radioactive doses of intrinsically radiolabeled 198Au nanoparticles for poten-tial use in targeted cancer therapy. Having a uniform shape and size of nanoparticles is desirable in nanomedicine as otherwise the observed biological effect would be an average of the effects of different species [6]. However, most of the reported procedures which involve better shape and size control involve numerous steps which are difficult to perform in a hot-cell facility while attempting to synthesize large radioactive doses of intrinsically radiolabeled nanoparticles. Therefore, a facile approach for radiosynthesis was developed in the present study even though
    A
    Magnetization [Mxy(t)] 
    PBS
    PBS
    Serum
    Serum
    C
    Hydrodynamic diameter (nm) 
    Fig. 3. (A) Measurement of magnetic T2 relaxation time for AuNP-RGD in mouse serum and PBS media at 25 °C. (B) Variation in T2 relaxation time of AuNP-RGD with time when mixed with excess volume of mouse serum and PBS. (C) Variation in hydrodynamic diameter of AuNP-RGD over a period of 7 days when incubated in excess volume of PBS.
    there was some compromise on the shape and size of the nanoparticles.
    3.2. Cell viability study with AuNP-RGD
    For proving the potential utility of AuNP-RGD as a new agent for can-cer targeting, the viability of A549 and CHO UNC1999 (MTT assay) was exam-ined at various concentrations of the nanoparticles (Fig. 4). The viability of A549 cells was not significantly affected by co-incubation with 0– 200 μg/mL of AuNP-RGD for 24 h, whereas the CHO cells exhibited a small decrease only when incubated with relatively high concentrations of the nanoparticles. The results of this study indicated the high in vitro biocompatibility of AuNP-RGD and thus demonstrated its suitability for biomedical applications.
    × 1014 n·cm−2·s−1 for 7 d in the Dhruva reactor at Bhabha Atomic Re-search Centre (Table 1). Production of 198Au was carried out in 6 differ-ent batches and consistent yields were obtained in all the batches. If translated for clinical studies, the quantity of 198Au produced in a typical batch would be adequate for synthesis of clinically relevant doses of in-trinsically radiolabeled 198AuNP-RGD for administration to multiple patients.
    3.4. Synthesis and quality control of intrinsically radiolabeled 198AuNP-RGD
    Clinically relevant doses (N37 GBq which is suitable for treatment in multiple patients) of 198AuNP-RGD could be synthesized (Table 1). The overall yield of 198AuNP-RGD was N85% and reproducible results were obtained in all the batches.
    Prior to using 198AuNP-RGD for preclinical studies, stringent quality control analysis is essential in order to determine the suitability of the intrinsically radiolabeled nanoparticles for such applications. The radionuclidic purity of 198AuNP-RGD was assayed by γ-spectrometry using HPGe detector (Fig. 5). The γ-spectrum showed peaks corre-sponding to 198Au. However, the 158.4 keV and 208.2 keV peaks corre-sponding to 199Au were also detected indicating the presence of this radioisotope as a radionuclidic impurity in 198AuNP-RGD. In fact, the co-production of 199Au along with 198Au cannot be avoided as it is formed by double neutron capture reaction on 197Au target. Neverthe-less, the level of this radionuclidic impurity in 198AuNP-RGD is low
    Concentration (g/mL)
    Fig. 4. Cell viability assay carried out after incubation of A549 and CHO cells with AuNP-RGD (concentration range: 0–200 μg/mL) for 48 h. 
    and therefore its presence is not expected to have any serious impact to-wards practical utilization of the intrinsically radiolabeled nanoparti-cles. The radiochemical purity of 198AuNP-RGD was determined by radio-TLC developed in saline in 0.02 M HCl medium. The radio-TLC pat-terns of 198AuNP-RGD and free 198Au solution are shown in Fig. 6. By comparison of the chromatographic patterns, the radiochemical purity of 198AuNP-RGD was determined to be N99%. Size exclusion chromato-graphic pattern obtained by passing 198AuNP-RGD through PD-10 col-umn further corroborated the results of radiochemical purity studies by radio-TLC technique (Fig. 7). After passing through the 0.22 μm filter, 198AuNP-RGD solution was found to be sterile. The level of endotoxins in 198AuNP-RGD samples was b5 endotoxin unit (EU)/mL, which is within the acceptable limit for clinical use [17].