(643h) Fabrication and Characterization of Quantum Dot-Loaded Polymeric Nanocarriers

The use of nanoparticles in drug delivery can address many of the difficulties faced by traditional drug delivery methods such as systemic toxicity, transport limitations, and drug solubility. By loading drugs into biocompatible polymeric nanoparticles, drugs that were previously not usable due to their solubility or toxicity can now be used. Because the properties of the polymeric carriers can be manipulated, it is possible now to improve circulatory residence time, targeting, and drug-release depending upon application needs. However, many questions about on nanoparticle biodistribution and accumulation in tissues still remain and so a method for tracking these particles is necessary. Fluorescent imaging agents are currently of high interest in biological application studies due to their high contrast and resolution potential. Quantum dots (QDs) such as CdSe nanoparticles coated with ZnS are particularly interesting due to their high quantum yield and photostability which allows for minimal use of materials while achieving good detectability. However, the presence of heavy metals in QDs pose a potential toxicity problem. Hydrophobic modification of quantum dots can be used to trap them in a hydrophobic polymer core and therefore mitigate the concern for high toxicity effects while making use of their fluorescence for particle tracking and biodistribution studies.

We report the fabrication of colloidally-stable core-shell nanoparticles comprised of hydrophobically modified CdSe/ZnS quantum dots and the poly(ethylene glycol)-b-poly(D,L-lactide) block copolymer [mPEG(5 kDa)-b-PDLLA(10 kDa)]. The CdSe/ZnS quantum dots with diameter ~ 5 nm were obtained from a commercial source. The block copolymer was synthesized by ring-opening polymerization of D,L-lactide in the presence of mPEG using stannous octoate as the catalyst. The nanoparticles were prepared by Flash Nanoprecipitation which takes advantage of low solubilities of the hydrophobically modified QDs to encapsulate them in the hydrophobic PDLLA cores of the nanoparticles. The method’s scalability and efficacy in producing well-defined nanoparticles makes it a particularly attractive approach.

Nanoparticles were fabricated with hydrodynamic diameters in the range of 80-100 nm and polydispersity indices less than 0.2 as measured by dynamic light scattering. The zeta potentials of the particles were typically -20 mV in phosphate buffered saline diluted 100X. Fluorescence studies show that the nanoparticles containing the quantum dots could be excited at wavelengths of 480 nm and below and had an emission peak at 530 nm. These nanoparticles were colloidally stable in cell-growth media supplemented with fetal bovine serum (FBS) for periods up to 12 hours. Cell culture studies with macrophage cells show that they were not immunogenic. ELISA tests showed that the nanoparticles induced levels of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFa) in both M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophage cells similar to those of mock negative control experiments. Further results will be presented on how these nanoparticles are taken up by macrophages.