Hydrophobic Cysteine Poly(disulfide)-based Redox-Hypersensitive Nanoparticle Platform for Cancer Theranostics.

Selective tumor targeting and drug delivery are critical for cancer treatment. Stimulus-sensitive nanoparticle (NP) systems have been designed to specifically respond to significant abnormalities in the tumor microenvironment, which could dramatically improve therapeutic performance in terms of enhanced efficiency, targetability, and reduced side-effects. We report the development of a novel L-cysteine-based poly (disulfide amide) (Cys-PDSA) family for fabricating redox-triggered NPs, with high hydrophobic drug loading capacity (up to 25 wt% docetaxel) and tunable properties. The polymers are synthesized through one-step rapid polycondensation of two nontoxic building blocks: L-cystine ester and versatile fatty diacids, which make the polymer redox responsive and give it a tunable polymer structure, respectively. Alterations to the diacid structure could rationally tune the physicochemical properties of the polymers and the corresponding NPs, leading to the control of NP size, hydrophobicity, degradation rate, redox response, and secondary self-assembly after NP reductive dissociation. In vitro and in vivo results demonstrate these NPs' excellent biocompatibility, high selectivity of redox-triggered drug release, and significant anticancer performance. This system provides a promising strategy for advanced anticancer theranostic applications.

DNA stabilized silver nanoclusters for ratiometric and visual detection of Hg²âº and its immobilization in hydrogels.

DNA oligomers are particularly interesting templates for making silver nanoclusters (AgNCs) as different emission colors can be obtained by varying the DNA sequence. Many AgNCs have been used as Hg²âº sensors since Hg²âº induces fluorescence quenching. From an analytical chemistry standpoint, however, these 'light off' sensors are undesirable. In this work, taking advantage of the fact that some AgNCs are not as effectively quenched by Hg²âº, we design a sensor with AgNCs containing two emission peaks. The red peak is strongly quenched by Hg²âº while the green peak shows a concomitant increase, producing an orange-to-green visual fluorescence transformation. Using this AgNC, we demonstrate ratiometric detection with a detection limit of 4 nM Hg²âº. This sensor is further immobilized in a hydrogel matrix and this gel is also capable of detecting Hg²âº with a visual response.

Correlation of photobleaching, oxidation and metal induced fluorescence quenching of DNA-templated silver nanoclusters.

Few-atom noble metal nanoclusters have attracted a lot of interest due to their potential applications in biosensor development, imaging and catalysis. DNA-templated silver nanoclusters (AgNCs) are of particular interest as different emission colors can be obtained by changing the DNA sequence. A popular analytical application is fluorescence quenching by Hg(2+), where d(10)-d(10) metallophilic interaction has often been proposed for associating Hg(2+) with nanoclusters. However, it cannot explain the lack of response to other d(10) ions such as Zn(2+) and Cd(2+). In our effort to elucidate the quenching mechanism, we studied a total of eight AgNCs prepared by different hairpin DNA sequences; they showed different sensitivity to Hg(2+), and DNA with a larger cytosine loop size produced more sensitive AgNCs. In all the cases, samples strongly quenched by Hg(2+) were also more easily photobleached. Light of shorter wavelengths bleached AgNCs more potently, and photobleached samples can be recovered by NaBH4. Strong fluorescence quenching was also observed with high redox potential metal ions such as Ag(+), Au(3+), Cu(2+) and Hg(2+), but not with low redox potential ions. Such metal induced quenching cannot be recovered by NaBH4. Electronic absorption and mass spectrometry studies offered further insights into the oxidation reaction. Our results correlate many important experimental observations and will fuel the further growth of this field.

Blue emitting gold nanoclusters templated by poly-cytosine DNA at low pH and poly-adenine DNA at neutral pH.

Blue fluorescent gold nanoclusters were prepared in the presence of poly-cytosine DNAs at low pH and poly-adenine at neutral pH using citrate as the reducing agent; various buffer conditions affecting the synthesis have been explored.