Quantum dots have been used in biomedical research for imaging, diagnostics and sensing purposes. However, concerns over the cytotoxicity of their heavy metal constituents and conflicting results from in vitro and small animal toxicity studies have limited their translation towards clinical applications. Here, we show in a pilot study that rhesus macaques injected with phospholipid micelle-encapsulated CdSe/CdS/ZnS quantum dots do not exhibit evidence of toxicity. Blood and biochemical markers remained within normal ranges following treatment, and histology of major organs after 90 days showed no abnormalities. Our results show that acute toxicity of these quantum dots in vivo can be minimal. However, chemical analysis revealed that most of the initial dose of cadmium remained in the liver, spleen and kidneys after 90 days. This means that the breakdown and clearance of quantum dots is quite slow, suggesting that longer-term studies will be required to determine the ultimate fate of these heavy metals and the impact of their persistence in primates.

This contribution introduces the use of cadmium-free CuInS(2) quantum dots (QDs) for targeted and multiplexed optical imaging of tumors in mice. CuInS(2)/ZnS QDs were synthesized in a non-aqueous phase using the hot colloidal synthesis method. Previous challenges involving stable aqueous dispersion of highly luminescent CuInS(2)/ZnS QDs have been overcome by encapsulating them within functionalized phospholipid micelles, which also facilitated their conjugation with folic acid for targeted delivery. Luminescence signals of QDs of multiple colors were readily differentiated from background autofluorescence in whole animal optical imaging. In addition, two-photon excitation studies revealed that the prepared water-dispersible QDs are suitable for two-photon in vitro and in vivo imaging. This study demonstrates the important key steps in realizing of the potential of CuInS(2) QDs as low-toxicity, photostable, cadmium-free and highly luminescent probes for cancer detection and sensing.

Among the five serine incorporator (SERINC) family members, SERINC5 (Ser5) was reported to strongly inhibit HIV-1 replication, which is counteracted by Nef. Ser5 produces 5 alternatively spliced isoforms: Ser5-001 has 10 putative transmembrane domains, whereas Ser5-004, -005, -008a, and -008b do not have the last one. Here, we confirmed the strong Ser5 anti-HIV-1 activity and investigated its isoforms' expression and antiviral activities. It was found that Ser5-001 transcripts were detected at least 10-fold more than the other isoforms by real-time quantitative PCR. When Ser5-001 and its two isoforms Ser5-005 and Ser5-008a were expressed from the same mammalian expression vector, only Ser5-001 was stably expressed, whereas the others were poorly expressed due to rapid degradation. In addition, unlike the other isoforms, which are located mainly in the cytoplasm, Ser5-001 is localized primarily to the plasma membrane. To map the critical determinant, Ser5 mutants bearing C-terminal deletions were created. It was found that the 10th transmembrane domain is required for Ser5 stable expression and plasma membrane localization. As expected, only Ser5-001 strongly inhibits HIV-1 infectivity, whereas the other Ser5 isoforms and mutants that do not have the 10th transmembrane domain show very poor activity. It was also observed that the Nef counteractive activity could be easily saturated by Ser5 overexpression. Thus, we conclude that Ser5-001 is the predominant antiviral isoform that restricts HIV-1, and the 10th transmembrane domain plays a critical role in this process by regulating its protein stability and plasma membrane targeting. IMPORTANCE Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) express a small protein, Nef, to enhance viral pathogenesis in vivo.Nef has an important in vitro function, which is to make virus particles more infectious, but the mechanism has been unclear. Recently, Nef was reported to counteract a novel anti-HIV host protein, SERINC5 (Ser5). Ser5 has five alternatively spliced isoforms, Ser5-001, -004, -005, -008a, and -008b, and only Ser5-001 has an extra C-terminal transmembrane domain. We now show that the Ser5-001 transcripts are produced at least 10-fold more than the others, and only Ser5-001 produces stable proteins that are targeted to the plasma membrane. Importantly, only Ser5-001 shows strong anti-HIV-1 activity. We further demonstrate that the extra transmembrane domain is required for Ser5 stable expression and plasma membrane localization. These results suggest that plasma membrane localization is required for Ser5 antiviral activity, and Ser5-001 is the predominant isoform that contributes to the activity.KEYWORDS HIV-1, Nef, SERINC3, SERINC5, infectivity, restriction factor

The usually measured attenuation (extinction) spectra of gold nanorods in water include two unresolving contributions: absorption and scattering. The present study is to separate these two contributions by measuring the total scattering losses as a function of wavelengths. Knowing the total-attenuation spectrum and the scattering-loss spectrum, the pure absorption spectrum can be finally determined for a given sample system. Two approaches are employed for experimentally estimating the pure scattering losses: one is direct measurement using a calibrated large-area photodetector to collect the scattered energy along a certain solid angle; the other is comparison measurement by using polystyrene microspheres in water as a standard sample whose scattering cross section is known well. These two methods have given nearly the same results and are finally compared with the theoretical calculations.