Promising New NanoTheranostic Quantum dots Based on Ag2S-PEG-FA

Introduction There is a tremendous effort in the development of nontoxic QDs emitting in the near-infrared (NIR) for medical use, both as an optical imaging and as gene/drug delivery agents. This provides an opportunity for... [ view full abstract ]

Introduction
There is a tremendous effort in the development of nontoxic QDs emitting in the near-infrared (NIR) for medical use, both as an optical imaging and as gene/drug delivery agents. This provides an opportunity for deep tissue penetration and reduction of the tissue autofluoresence. Other important issues in practical application of QDs are the overall size, blood circulation, molecular targeting and stability. Ag2S quantum dots emerged as the most promising QDs in the last 5 years. They emit in the NIR region and are highly cyto-hemocompatible. Here, we report the first direct and size tuned synthesis of PEG coated Ag2S NIR QDs and their theranostic use for optical imaging and folic acid (FA) targeted DOX delivery to HeLa cells.

Methods
Ag2S, Na2S and MPEG-SH were dissolved in DIW under Argon at different ratios and at pH values between 3 or 7.5. Reactions were run at 90°C. For FA tagging 30mol% HOOC-PEG-SH was used in the coating and FA was conjugated with EDC/NHS. DOX.HCl was loaded to QDs at pH 6. MTT assay was used to analyze cytotoxicity of particles in HeLa and NIH-3T3 cells.

Results and Discussions
In the size and emission tunning of QDs, increasing Ag/S decreased the particle size. Synthesis at acidic pH produced larger QDs with stronger emission. Increasing PEG molecular weight from 2000 Da to 5000 Da increased the QY about 40 % with 43 nm red shift in peak maxima. All QDs were below 50 nm. Between 5-25 g/mL Ag dose, no significant cytotoxicity was observed in either cell lines. Folate targeted and DOX loaded particles delivered DOX to the cells more effectively than untagged QDs. About 50% drop in the viability with only 15 nM DOX was achieved with FA targeting.

Conclusions
Here, in a simple one step aq. synthesis, PEGylated Ag2S NIR QDs were synthesized with emission maxima between 847-930 nm with QY as high as 65 %, using HS-PEG coating. These particles were non-toxic to HeLa and NIH/3T3 even at mg range. Internalized particles, generates a strong NIR signal. FA-tagged particles showed excellent drug efficiency coupled with receptor mediated uptake.