Aneta Borecki

A molecular precursor approach for the synthesis of composition-controlled ZnxCd1−xS and ZnxCd1−xSe nanoparticles

Ternary ZnxCd1−xS and ZnxCd1−xSe nanoparticles have been synthesized using a low temperature molecular precursor approach. The co-injection of silylated metal chalcogenolate complexes [(N,N′-TMEDA)Zn(ESiMe3)2] (E = S, 1; E = Se, 2) and [(N,N′-TMEDA)Cd(ESiMe3)2] (E = S, 3; E = Se, 4) to solutions of (N,N′-TMEDA)M(OAc)2 (M = Zn, Cd) in THF resulted in the formation of nanocrystalline quantum dots with particle sizes in the 2–3 nm range. Nanoparticles with Zn mole fractions (x) ranging from 0.95 to 0.05 can be achieved via manipulation of the reaction stoichiometry of 1(2) and 3(4). The size uniformity of the ternary nanoparticles permits control of the absorption properties by changing the metal ion composition. UV-visible and NMR spectroscopy, thermogravimetric analysis as well as X-ray and electron diffraction studies provide substantial evidence that the Zn(II) and Cd(II) ions are homogeneously mixed both within the cores of the nanoparticles and at the particle surfaces. Further control of the optical properties of the ternary materials was achieved via the growth of the particles in hot hexadecylamine while maintaining the Zn/Cd ratio.

Photodegradable poly(ester amide)s for indirect light-triggered release of paclitaxel

Stimuli-responsive micelles formed from amphiphilic copolymers are promising materials for the delivery of drugs and can potentially lead to enhanced biological properties and efficacies. Among the available stimuli, light is particularly attractive, as it can be highly localized in time and space. Described here is the development of a new fully photodegradable poly(ester amide) (PEA) backbone. Degradation in response to UV light was demonstrated by UV-vis spectroscopy, NMR spectroscopy, and size exclusion chromatography. Upon the incorporation of an L-aspartic acid-based monomer, providing carboxylic acid functional handles along the PEA backbone, the anticancer drug paclitaxel (PTX) was conjugated by an ester linkage and poly(ethylene oxide) was conjugated via an amide linkage to impart amphiphilicity. Micelles were prepared from the resulting amphiphilic copolymer and were demonstrated to break down in response to UV irradiation. This led to accelerated release of PTX, which is believed to result from the increased exposure of the ester linkages to water upon micelle disruption. The in vitro toxicities of both UV irradiated and non-irradiated micelles were also evaluated and compared to PTX in Cremophor EL–ethanol and to micelles without drug.

Tuning the hydrophobic cores of self-immolative polyglyoxylate assemblies

Polyglyoxylates are a recently-introduced class of self-immolative polymers, that depolymerize to small molecules upon the cleavage of a stimuli-responsive end-cap from the polymer terminus. The incorporation of different pendant ester groups or other aldehyde monomers offers the potential to tune the polymer properties, but this remains largely unexplored. With the goal of tuning the self-assembly and drug-loading properties of polyglyoxylate block copolymers, we explored the polymerization and copolymerization of n-butyl glyoxylate, L-menthyl glyoxylate, and chloral with ethyl glyoxylate to form UV light-responsive polyglyoxylates. The resulting polymers were coupled to poly(ethylene glycol) to afford amphiphilic block copolymers. Self-assembly of the different copolymers was studied and although each system formed solid particles, the cores of the assemblies differed in their stability, hydrophobicity, and their ability to load the hydrophobic drug celecoxib. All systems depolymerized and released the drug in response to UV light. The toxicity profiles for the assemblies were also evaluated using MDA-MB-231 cells. Overall, this work demonstrates that the properties of polyglyoxylates and their assemblies can be readily tuned through the incorporation of new monomers, thereby providing a promising platform for drug delivery and other applications.

Hybrid Polyester Self-Immolative Polymer Nanoparticles for Controlled Drug Release

Delivery systems have been developed to address problematic properties of drugs, but the specific release of drugs at their targets is still a challenge. Polymers that depolymerize end-to-end in response to the cleavage of stimuli-responsive end-caps from their termini, commonly referred to as self-immolative polymers, offer high sensitivity to stimuli and have potential for the development of new high-performance delivery systems. In this work, we prepared hybrid particles composed of varying ratios of self-immolative poly(ethyl glyoxylate) (PEtG) and slowly degrading poly(d,l-lactic acid) (PLA). These systems were designed to provide a dual release mechanism consisting of a rapid burst release of drug from the PEtG domains and a slower release from the PLA domains. Using end-caps responsive to UV light and reducing thiols, it was found that triggered particles exhibited partial degradation, as indicated by a reduction in their dynamic light-scattering count rate that depended on the PEtG:PLA ratio. The particles were also shown to release the hydrophobic dye Nile red and the drug celecoxib in a manner that depended on triggering and the PEtG:PLA ratio. In vitro toxicity assays showed an effect of the stimuli on the toxicity of the celecoxib-loaded particles but also suggested it would be ideal to replace the sodium cholate surfactant that was used in the particle synthesis procedure in order to reduce the background toxicity of the delivery system. Overall, these hybrid systems show promise for tuning and controlling the release of drugs in response to stimuli.