Synthesis and Characterization of PEGylated Near-IR-Emitting Ag2S Quantum Dots for Tumor Imaging and Therapy

摘要

Introduction Near-infrared (NIR) emitting semiconductor quantum dots (QPs) have emerged as a new class of fluorescent probes in recent years due to better penetration depth into the tissue and elimination or significant reduction of tissue autofluorescence. Ag2S quantum dots are the most popular NIR emitting quantum dots in recent years because dramatically improved cytocompatibility compared to heavy metal containing, more traditional QPs such as PbS, PbSe, CdHgTe.PM Previously, we have developed cationic polyethyleneimine (PEI)-25 kPa and 2MPA coated Ag2S QPs with high quantum yields. However, cationic QPs show some toxicity. In order to reduce such toxicity and prevent adsorption of blood components, we pegylated the cationic Ag2S QPs. PEGylation also enabled Doxorubicin® (Pox) loading to these NIR QPs. Hence, PEG-PEI/2MPA coated aqueous Ag2S NIRQPs showed enhanced cytocompatability, theranostic and diagnostic potential. Materials Branched polyethyleneimine (PEI) (Mw 25 kPa) and N,N'-carbonyldiimidazole (CPI) were obtained from Aldrich. Methoxy polyethylene glycol (mPEG-OH, 2 kP) and chloroform were purchased from Rapp Polymere and Merck Millipore, respectively. Methods PEI and 2-MPA coated Ag2S QPs have been synthesized according to our previos report. PEGylation was performed using CPI chemistry by activation of hydroxyl terminal groups of the mPEG with CPI and conjugation of activated mPEG to QPs. Finally, washed samples were loaded with Pox. All cytotoxicity and optical imaging studies were performed with HeLa cells. Results PEI/2MPA Ag2S QPs have been conjugated with mPEG using CPI chemistry. NMR proved the conjugation. Particles were stable and highly luminescent even after PEGylation (Figure 1 a). Poxorubicin was loaded in PEGylated particles in high efficiency (Figure 1b). PEGylation improved the viability of HeLa cells especially at high doses (Figure 1c). Yet, Pox reduced viability. Piscussion In this study, PEI and 2MPA coated and PEGylated Ag2S QPs have been developed as new theranostic nanoparticles which allows optical imaging at the NIR window and effective delivery of a cancer drug into cells. Particles were stable in aqueous medium and luminesce strongly around 820 nm. Pox which is mostly used cancer drug was loaded to the PEGylated particles to evaluate the QPs as a cancer drug delivery agent. In addition to increased viability of cells after PEGylation, Pox loading increased the toxicty, provin g effcient delivery of Pox into the cells which was confirmed by confocal microscopy (Figure 1d). The drug release and apoptosisecrosis studies will be performed as next steps. Conclusion As a conclusion, we have developed PEGylated cationic Ag2S QPs with high stability and strong luminesence in the NIR region. Such particles have high cytocompatability to be used as safe optical imaging and drug delivery agents. This was demonstrated with Pox loading and delivery into HeLa cells.