Jianxu Zhang

Co-assembled hybrids of proteins and carbon dots for intracellular protein delivery

A general and simple strategy for intracellular protein delivery was developed by co-assembling carbon dots and proteins. Compared to free proteins, this delivery system can protect proteins against enzymatic hydrolysis and effectively deliver EGFP into HeLa cells.

Photothermally induced accumulation and retention of polymeric nanoparticles in tumors for long-term fluorescence imaging

The development of long-term tumor imaging is of great importance for effective theranostic systems. In this study, a temperature-responsive poly(ether amine) with a phase transition temperature around 43 °C was used to encapsulate indocyanine green (ICG), which is a near infrared fluorescent and photothermal agent. Upon photothermal treatment, the polymeric nanoparticles underwent an increase in size from the nano- to the microscale. The prepared ICG-loaded PEAs exhibited significant stability against photobleaching and excellent NIR imaging ability. The increase in particle size resulted in the accumulation and retention of nanoparticles at the tumor site upon photothermal treatment. The accumulation of nanoparticles facilitated long-term imaging of the tumor for up to 30 days after one injection. This study highlights the potential of the rational design of polymer nanoparticles for bioimaging and diagnostics.

GSH-triggered size increase of porphyrin-containing nanosystems for enhanced retention and photodynamic activity

Long retention of therapeutic agents in tumors is imperative for improving the therapeutic index. In this work, the GSH responsive porphyrin molecule (TPP 1) was synthesized, which is amphiphilic and linked by a disulfide bond. TPP 1 molecules could self-assemble into nanoparticles (TPP 1 NPs) with a size of about 100 nm in aqueous solution. The TPP 1 NPs exhibited high stability under different conditions and could form into large microparticles in the presence of glutathione (GSH). The TPP 1 NPs could be internalized by cancer cells, and they emitted enhanced red fluorescence compared to that of TPP 2 NPs (non-sensitive NPs) when cells were pretreated with GSH. In addition, in vitro MTT assays showed that TPP 1 NPs were biocompatible and could further be used as photosensitizers in nanoparticle formation. The cellular photodynamic activity of TPP 1 NPs was obviously higher than that of TPP 2 NPs, due to the increasing retention of TPP in cancer cells, which will generate more reactive oxygen species in cancer cells under light irradiation. These results highlight the potential of developing stimulus responsive nanoparticles for enhanced retention and improved therapeutic outcome.

Hybrids of carbon dots with subunit B of ricin toxin for enhanced immunomodulatory activity

Although Ricin toxin binding subunit B (RTB) can promote the activation of macrophages and modulate the cell-mediated immunity, its applications are severely limited due to the intrinsic properties of proteins, like poor stability and low efficacy of cellular uptake. In this work, the stable nanoparticles were prepared by supramolecular assembling of carbon dots (CDs) and RTB. The formed CDs-RTB possesses robust stability and can protect RTB against enzymatic hydrolysis. More importantly, CDs-RTB can promote macrophages proliferation, improve the generation of NO, IL-6 and TNF-α in RAW264.7 cells and increase the expression of mRNA, indicating the enhanced immunomodulatory activity of CDs-RTB. This work highlights the potential of using CDs as a simple and stable platform to assemble RTB and effectively promotes the application of RTB as the immunostimulant.

Nanoscale Melittin@Zeolitic Imidazolate Frameworks for Enhanced Anticancer Activity and Mechanism Analysis

The cytolytic peptide melittin (MLT) is an important candidate of anticancer drug owing to its hemolytic properties. Nevertheless, its clinical applications are severely restricted as a result of its nonspecific toxicities like hemolysis. In this work, we reported MLT-loaded zeolitic imidazolate framework-8 (MLT@ZIF-8) nanoparticles (NPs). The formed MLT@ZIF-8 NPs not only possess excellent stability but also efficiently inhibit the hemolysis bioactivity of MLT. Confocal scanning imaging and cytotoxicity experiments revealed that as-synthesized MLT@ZIF-8 NPs exhibit enhanced cellular uptake and cytotoxicity toward cancer cells compared to MLT. The mechanism is well investigated by a series of transcriptome analysis, which indicates that MLT@ZIF-8 NPs can regulate the expression of 3383 genes, and the PI3K/Akt-regulated p53 pathway is involved in MLT@ZIF-8 NPs induced A549 cells apoptosis. Finally, MLT@ZIF-8 NPs exhibit enhanced antitumor activity than free MLT in vivo, while no obvious systemic toxicity has been found. This work emphasizes the great potential of utilizing MOF as a simple and efficient nanoplatform for deliverying cytolytic peptides in cancer treatment, and also the investigation on the antitumor mechanism could provide theoretical support for clinical usage of MLT.