We review the syntheses, optical properties, and biological applications of cadmium selenide (CdSe) and cadmium selenide-zinc sulfide (CdSe-ZnS) quantum dots (QDs) and gold (Au) and silver (Ag) nanoparticles (NPs). Specifically, we selected the syntheses of QDs and Au and Ag NPs in aqueous and organic phases, size- and shape-dependent photoluminescence (PL) of QDs and plasmon of metal NPs, and their bioimaging applications. The PL properties of QDs are discussed with reference to their band gap structure and various electronic transitions, relations of PL and photoactivated PL with surface defects, and blinking of single QDs. Optical properties of Ag and Au NPs are discussed with reference to their size- and shape-dependent surface plasmon bands, electron dynamics and relaxation, and surface-enhanced Raman scattering (SERS). The bioimaging applications are discussed with reference to in vitro and in vivo imaging of live cells, and in vivo imaging of cancers, tumor vasculature, and lymph nodes. Other aspects of the review are in vivo deep tissue imaging, multiphoton excitation, NIR fluorescence and SERS imaging, and toxic effects of NPs and their clearance from the body.

Strand breakages and nucleobase damages in plasmid DNA (pDNA) by CdSe-ZnS quantum dots (QDs) are investigated under different conditions of photoactivation. Here, streptavidin functionalized CdSe-ZnS QDs are conjugated to biotinylated pDNA, and photosensitized strand breakages and nucleobase damages in the conjugates are investigated using atomic force microscopy (AFM) imaging, gel electrophoreses analyses, and assay of reactive oxygen intermediates (ROI). Also, reactions of photoactivated pDNA-QD conjugates with base excision repair enzymes such as formamidopyrimidine glycosylase (Fpg) and endonuclease III (Endo III) show damages of purine and pyrimidine bases. The base excision repair enzymes recognize and remove the damaged bases. The base excision reactions of photoactivated pDNA-QD conjugates resulted in pDNA strand breakages, which appeared as sheared bands in agarose gel images. On the basis of AFM imaging, reactions of Fpg and Endo III with damaged pDNA, ROI assay, and literature reports, we attribute the breakage and damage of pDNA to its reactions with ROI. The production of ROI by photoactivated QDs is confirmed by nitroblue tetrazolium (NBT) assay. The current work shows that photoactivation of QD-conjugated nucleic acids for an extended period of time is not favorable for their stability. On the other hand, photoinduced production of ROI by QDs is an emerging research area with potential applications in the photodynamic therapy of cancer. In this regard, photosensitized damage of pDNA observed in the current work shows possibilities of QDs in nucleus-targeted photodynamic therapy.

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Efficient intracellular delivery of quantum dots (QDs) and unravelling the mechanism underlying the intracellular delivery are essential for advancing the applications of QDs toward in vivo imaging and therapeutic interventions. Here, we show that clathrin-mediated endocytosis is the most important pathway for the intracellular delivery of peptide-conjugated QDs. We selected an insect neuropeptide, namely, allatostatin (AST1, APSGAQRLYG FGL-NH(2)), conjugated it with CdSe-ZnS QDs, and investigated the intracellular delivery of the conjugate in living cells such as human epidermoid ovarian carcinoma cells (A431) and mouse embryonic fibroblast cells (3T3). We selected AST1 to investigate the intracellular delivery of QDs because we recently found it to be efficient for delivering QDs in living mammalian cells. Also, the receptors of AST1 in insects show functional and sequence similarity to G-protein-coupled galanin receptors in mammals. We employed flow cytometry and fluorescence microscopy and investigated the contributions of clathrin-mediated endocytosis, receptor-mediated endocytosis, and charge-based cell penetration or transduction to the intracellular delivery of QD-AST1 conjugates. Interestingly, the intracellular delivery was suppressed by approximately 57% when we inhibited the regulatory enzyme phosphoinositide 3-kinase (PI3K) with wortmannin and blocked the formation of clathrin-coated vesicles. In parallel, we investigated clathrin-mediated endocytosis by colocalizing QD560-labeled clathrin heavy-chain antibody and QD605-AST1. We also estimated galanin receptor-mediated endocytosis of QD-AST1 at <10% by blocking the cells with a galanin antagonist and transduction at <30% by both removing the charge of the peptide due to arginine and suppressing the cell-surface charge due to glycosaminoglycan. In short, the current work shows that multiple pathways are involved in the intracellular delivery of peptide-conjugated QDs, among which clathrin-mediated endocytosis is the most important.