The fluorescent quantum dots (QDs) delivered small interfering RNAs (siRNAs) targeting β-secretase (BACE1) to achieve high transfection efficiency of siRNAs and reduction of β-amyloid (Aβ) in nerve cells. The CdSe/ZnS QDs with the conjugation of amino-polyethylene glycol (PEG) were synthesized. Negatively charged siRNAs were electrostatically adsorbed to the surface of QDs to develop QD-PEG/siRNA nanoplexes. The QD-PEG/siRNAs nanoplexes significantly promote the transfection efficiency of siRNA, and the siRNAs from non-packaged nanoplexes were widely distributed in cell bodies and processes and efficiently silenced BACE1 gene, leading to the reduction of Aβ. The biodegradable PEG polymer coating could protect QDs from being exposed to the intracellular environment and restrained the release of toxic Cd2⁺. Therefore, the QD-PEG/siRNA nanoplexes reported here might serve as ideal carriers for siRNAs. We developed a novel method of siRNA delivery into nerve cells. We first reported that the QD-PEG/siRNA nanoplexes were generated by the electrostatic interaction and inhibited the Alzheimer's disease (AD)-associated BACE1 gene. We also first revealed the dynamics of QD-PEG/siRNAs within nerve cells via confocal microscopy and the ultrastructural evidences under transmission electron microscopy (TEM). This technology might hold promise for the treatment of neurodegenerative diseases such as AD.

Thionated perylenediimides (PDIs) can potentially generate thermal and reactive oxygen species and thus can be used as theranostic agents for photothermal/photodynamic therapy. Herein, thionated cis-/trans-isomer PDI-CS and PDI-TS were designed and prepared to investigate thionation engineering on therapeutic performance. The results revealed that the photodynamic performance is less associated with the positon of sulfur atoms. By contrast, trans-isomer PDI-TS showed a photothermal conversion efficiency of up to 58.4%, which was 40% higher than that of PDI-CS (∼41.6%). An in vitro half-maximal inhibitory concentration of ∼7.78 μg mL⁻¹ was achieved for PDI-TS, which was 1.7-fold smaller than that of PDI-CS, strongly reasserting the regioisomer-modulated phototheranostic performance. Notably, the strong π–π and C⋯S interactions in PDI-TS nanoagents are essential factors attributed to their excellent photothermal performance, indicating that the optimization of non-bonding interactions is an ingenious way to improve phototheranostic performance. This work provides a facile means of creating thio-perylenediimides that possess excellent antitumor properties and a novel proof of concept to improve therapeutic performance through the optimization of non-bonding interactions.