Ge Gao

Fluorescence studies on the interaction between chlorpromazine and model cell membranes

In this work, the interaction between a commonly used multifunctional fluorescent drug chlorpromazine (CPZ) and model cell membranes (liposomes, giant unilamellar vesicles and supported lipid membranes) was investigated using various fluorescence-based techniques (steady-state and time-resolved spectroscopy, confocal microscopy and flow cytometry). It was found that CPZ could substantially quench the fluorescence of lipid membrane fluorophores while the drug’s own fluorescence signal was significantly enhanced upon membrane interaction. The drug contact-induced fluorescence quenching response of the membrane fluorophores can be explained by the coexistence of both static and dynamic quenching processes, while the fluorescence enhancement of CPZ is attributed to the change in environmental polarity. Both fatty acid (tail)- and headgroup-labeled fluorophores in the lipid membranes were quenched immediately after the introduction of CPZ, indicating that the CPZ molecules reside at the lipid interfacial region and can interact with both the headgroups and tails of the lipids. In addition, fluorescence quenching was partly recoverable by water washing, indicating that the association of the CPZ molecules with the lipid membrane is not very strong. On the other hand, the significantly enhanced fluorescence intensity of CPZ after insertion into the less polar lipid bilayer enabled us to directly visualize the location of the drug molecules interacting with cell membranes. The current study provides important molecular-level knowledge about CPZ–cell membrane interactions using various model cell membranes, and represents a typical example of deciphering the drug and cell membrane interaction mechanisms using various fluorescence-based techniques.

Self-Assembled Rose Bengal-Exopolysaccharide Nanoparticles for Improved Photodynamic Inactivation of Bacteria by Enhancing Singlet Oxygen Generation Directly in the Solution

It is of great value to develop new antibacterial photodynamic therapy (PDT) strategies to improve antibacterial PDT efficacy of noncationic photosensitizers without introducing cytotoxicity, which is a great challenge for current leading efforts on antimicrobial PDT based on cell surface engineering. In this research, the hydrophobic and anionic photosensitizer rose bengal (RB) was chemically conjugated with bacterial exopolysaccharide (EPS) to generate an amphiphilic and negatively charged compound EPS-RB that could self-assemble into nanoparticles (NPs) in solution. These EPS-RB NPs possessed an increased singlet oxygen generation property in solution. As a result, EPS-RB exhibited improved photoinactivation for both Gram-negative and Gram-positive bacteria, leading to a record low RB working concentration, 8 μM or 500 nM for Escherichia coli or Staphylococcus aureus, respectively. Upon light irradiation, more EPS-RB bound to the cell surface and penetrated into bacteria than RB, with EPS-RB staying around the cell surface of the most irradiated E. coli while entering all irradiated S. aureus. Both scanning electron microscopy and fluorescence confocal imaging results show that the cell membrane of E. coli was damaged heavily but not S. aureus. All of these observations indicate that both the enhanced singlet oxygen production of EPS-RB NPs in solution and their consequently increased membrane binding and cellular penetration into the bacteria through the damaged cell membrane contribute to their significantly improved bacterial photoinactivation efficiency. In addition, EPS-RB has low cytotoxicity and negligible hemolytic activity, showing great biocompatibility. Therefore, the construction of EPS-RB provides a new strategy for the PDT effectiveness improvement of the separated cell/sensitizer systems and thus the design of next-generation antimicrobial agents.

Near-infrared light-controllable on-demand antibiotics release using thermo-sensitive hydrogel-based drug reservoir for combating bacterial infection

A near-infrared (NIR) light-triggerable thermo-sensitive hydrogel-based drug reservoir that can realize on-demand antibiotics release and hyperthermia-assisted bacterial inactivation was prepared to combat bacterial infection and promote wound healing. The drug reservoir was fabricated by mixing ciprofloxacin (Cip, a potent antibiotic)-loaded polydopamine (PDA) nanoparticles (NPs) and glycol chitosan (GC) to form an injectable hydrogel (PDA NP-Cip/GC hydrogel, abbreviated as Gel-Cip). On the one hand, the positive charge of GC and the adsorbability of PDA NPs made bacteria be readily trapped on the surface of Gel-Cip. On the other hand, the Gel-Cip exhibited minimal leakage under physiological conditions, but could boost Cip release upon NIR light irradiation. Meanwhile, NIR light irradiation could activate the photothermal PDA NPs, and the generated local hyperthermia induced the destruction of the bacterial integrity, leading to bacterial inactivation in a synergistic way. Moreover, the exceptional bacterial killing activity and outstanding wound healing ability of the system were also verified by the S. aureus-infected mouse skin defect model. Taken together, the light-activatable hydrogel-based platform allows us to release antibiotics more precisely, eliminate bacteria more effectively, and inhibit bacteria-induced infections more persistently, which will advance the development of novel antibacterial agents and strategies.

Quantum Dots for Cancer Therapy and Bioimaging

Quantum dots (QDs) usually refer to very small nanoparticles of only few nanometers in size. The optical and electronic properties of QDs differ from those of larger particles. QDs will emit light of specific frequencies if electricity or light is applied to them, and these frequencies can be precisely tuned by changing the dots’ size, shape, and material, giving rise to many applications. In this chapter, apart from the most common QDs, e.g., the cadmium (Cd)-containing semiconductor QDs, other types of QDs, including silver chalcogenide quantum dots, carbon quantum dots, silicon quantum dots, black phosphorus quantum dots, germanium quantum dots, and polymer dots are also introduced with an emphasis on their cancer therapy and imaging applications.