Folate-Receptor-Mediated Delivery of InP Quantum Dots for Bioimaging Using Confocal and Two-Photon Microscopy

Abstract

A novel method for the synthesis of highly monodispersed hydrophillic InP-ZnS nanocrystals and their use as luminescence probes for live cell imaging is reported. Hydrophobic InP-ZnS nanocrystals are prepared by a new method that yields high-quality, luminescent core-shell nanocrystals within 6-8 h of total reaction time. Then by carefully manipulating the surface of these passivated nanocrystals, aqueous dispersions of folate-conjugated nanocrystals (folate-QDs) with high photostability are prepared. By use of confocal microscopy, we demonstrate the receptor-mediated delivery of folic acid conjugated quantum dots into folate-receptor-positive cell lines such as KB cells. These folate-QDs tend to accumulate in multi-vescicular bodies of KB cells after 6 h of incubation. Receptor-mediated delivery was confirmed by comparison with the uptake of these particles in folate-receptor-negative cell lines such as A549. Efficient two-photon excitation of these particles and two-photon imaging using these particles are also demonstrated. The use of these InP-ZnS nanoparticles and their efficient two-photon excitation can be potentially useful for deep tissue imaging for future in vivo studies.

Folate‐mediated cell uptake of shell‐crosslinked spheres and cylinders

“…9 By virtue of its high binding affinity toward the cell surface FR, which is overexpressed in a number of pathologic cells, selective delivery of nonspecific drugs that are conjugated to folate can be achieved. Derivatization of folate has been successfully exploited in the targeted delivery of proteins, 10,11 liposomes, 12 DNA nanoparticles, 13,14 synthetic organic 15,16 and inorganic nanoparticles, 17,18 and polymers. 19 As a targeting ligand, folate has many important advantages compared to monoclonal antibodies, such as low immunogenicity, high specificity, and resistance to denaturation, etc.…”

Immobilization of biomolecules on the surface of inorganic nanoparticles for biomedical applications

“…More importantly, no signs of morphological damage to the cells were observed upon treatment with various QDs, thereby illustrating their low cytotoxicity. The observed staining pattern is indeed due to the functionalized QDs, which have been demonstrated in several reports [91][92][93][94][95]. In addition to monoclonal antibody conjugation, QDs were also conjugated with a polyclonal antibody, anti-PSCA, for the specific targeting of human pancreatic cancer cells.…”

Passive tumor targeting and imaging by using mercaptosuccinic acid-coated near-infrared quantum dots

“…46 In this preparation, 4 mmol of MSA was dissolved in 5 mL of chloroform solution. The mixture was then stirred for 20 minutes, and 2 mL of concentrated (~20 mg/mL) QD dispersion was mixed with this solution.…”