Background: Although graphene quantum dots (GQDs) have received considerable research attention for their applications in various fields, the use of GQDs, such as nitrogen-doped GQDs (N-GQDs) and amino-functionalized N-GQDs (amino-N-GQDs), as photosensitizers to facilitate photodynamic therapy (PDT) has received limited research intention. To address this research gap, this study prepared novel amino-N-GQDs and investigated their properties. Methods: The amino-N-GQDs subjected to two-photon excitation (TPE) exhibited remarkable bactericidal capability in PDT. The bonding compositions of nitrogen and the amino-functionalized group played a critical role in their antimicrobial effects. Results: Compared with amino-group-free N-GQDs and amino-N-free GQDs, the amino-N-GQDs generated a higher amount of reactive oxygen species, demonstrating their superior efficacy for two-photon PDT. Additionally, the intrinsic luminescence properties and high photostability of the amino-N-GQDs demonstrate their suitability as an effective two-photon contrast agent for tracking bacteria during two-photon biomedical imaging. Conclusion: The amino-N-GQD and their remarkable properties may provide an efficient alternative approach for observing and easily eliminating malignant microbes in the future.

We fabricated nanomaterials comprising amino-functionalized and nitrogen-doped graphene quantum dots (amino-N-GQDs) and investigated their photostability and intrinsic luminescence in the near-infrared spectrum to determine their suitability as contrast agents in two-photon imaging (TPI). We observed that amino-N-GQDs with a higher amount of bonded nitrogen and amino-functionalized groups (6.2%) exhibited superior two-photon properties to those with a lower amount of such nitrogen and groups (4.9%). These materials were conjugated with polymers containing sulfur (polystyrene sulfonate, PSS) and nitrogen atoms (polyethylenimine, PEI), forming amino-N-GQD–PSS–PEI specimens (amino-N-GQD-polymers). The polymers exhibited a high quantum yield, remarkable stability, and notable two-photon properties and generated no reactive oxygen species, rendering them excellent two-photon contrast agents for bioimaging. An antiepidermal growth factor receptor (Ab_EGFR) was used for labeling to increase specificity. Two-photon imaging (TPI) of amino-N-GQD (6.2%)-polymer-Ab_EGFR-treated A431 cancer cells revealed remarkable brightness, intensity, and signal-to-noise ratios for each observation at a two-photon excitation power of 16.9 nJ pixel⁻¹ under 30 scans and a three-dimensional (3D) depth of 105 µm, indicating that amino-N-GQD (6.2%)-polymer-Ab_EGFR-treated cells can achieve two-photon luminescence with 71 times less power required for two-photon autofluorescence (1322.8 nJ pixel⁻¹ with 500 scans) of similar intensity. This economy can minimize photodamage to cells, rendering amino-N-GQD-polymers suitable for noninvasive 3D bioimaging.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), a rapidly progressing respiratory failure condition, results in a high mortality rate, especially in severe cases. Numerous trials have investigated various pharmacotherapy approaches, but their effectiveness remains uncertain. Here, we present an inhaled nanoformulation of fingolimod (FTY720)-nobiletin (NOB)- poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) with good biocompatibility and a sustained-release pharmacological effect. The formulation decreases the toxicity of FTY720 and increases the bioavailability of NOB since we use PLGA with a high biocompatibility to encapsulate FTY720 and NOB at the same time. In vitro, in comparison to treatment with the pure drug, we demonstrated that FTY720-NOB-PLGA NPs can reduce interleukin-6 (IL-6) and reactive oxygen species (ROS) release by macrophages after lipopolysaccharide (LPS) stimulation more efficiently. In vivo, we used an inhalation tower system that allowed the exposure of unanesthetized mice to aerosolized FTY720-NOB-PLGA NPs under controlled conditions. We demonstrated that inhaled FTY720-NOB-PLGA NPs can attenuate lung injury after LPS exposure by suppressing cytokine release, such as IL-6 and tumor necrosis factor-α (TNF-α). The trigger pathway of ALI, including nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and p38 mitogen-activated protein kinase, was also efficiently inhibited. Furthermore, the inhalation treatment provided a good safety profile, without detrimental effects on biochemical markers and lung function. We provided the feasibility of administering inhalation of NPs noninvasively with continuous monitoring of lung function. The aerosolized FTY720-NOB-PLGA NPs we developed show excellent promise for acute lung injury therapy in the future.

Background: Multidrug-resistant (MDR) bacterial strain is a serious medical problem. Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to many antibiotics and is often associated with several diseases such as arthritis, osteomyelitis, and endocarditis. The development of an alternative treatment for eliminating MDR bacteria such as MRSA has attracted a considerable amount of research attention. Moreover, the development of a material for highly efficient generation of reactive oxygen species (ROS) involving two-photon photodynamic therapy (PDT) is currently desirable. Materials and Methods: We present an example demonstrating that the use of water-soluble C ₆₀(OH) ₃₀ fullerenol with a 0.89 singlet oxygen quantum yield serving as a photosensitizer in PDT has the superior ability in effectively generating ROS. Results: It has ultra-low energy (228.80 nJ pixel^{− 1}) and can perform 900 scans under two-photon excitation (TPE) in the near-infrared region (760 nm) to completely eliminate the MDR species. Furthermore, the favorable two-photon properties are absorption of approximately 760 nm in wavelength, absolute cross-section of approximately 1187.50 Göeppert–Mayer units, lifetime of 6.640 ns, ratio of radiative to nonradiative decay rates of approximately 0.053, and two-photon stability under TPE. Conclusion: This enabled water-soluble C ₆₀(OH) ₃₀ fullerenol to act as a promising two-photon photosensitizer proceeding with PDT to easily eliminate MDR species.

Herein, GSH-sensitive hyaluronic acid-poly(lactic-co-glycolic acid) (HA-SS-PLGA) was synthesized. Surface modification of PLGA with hyaluronic acid produced a highly stable micelle at physiological pH while a micelle was destabilized at a higher GSH level. Fluorescence microscopy results showed that rhodamine-encapsulated micelle was taken up by brain cancer cells, while competitive inhibition was observed in the presence of free HA and free transferrin. In vitro cytotoxicity results revealed that transferrin-targeted nanoformulated AUY922 (TF-NP-AUY922) shows higher cytotoxicity than either free AUY922 or non-targeted AUY922-loaded micelles (NP-AUY922). In comparison to the control groups, free AUY922, TF-NP-AUY922 or NP-AUY922 treatment revealed the upregulation of HSP70, while the expression of HSP90 client proteins was simultaneously depleted. In addition, the treatment group induced caspase-dependent PARP cleavage and the upregulation of p53 expression, which plays a key role in apoptosis of brain cancer cells. In vivo and ex vivo biodistribution studies showed that cypate-loaded micelle was taken up and accumulated in the tumor regions. Furthermore, in vivo therapeutic efficacy studies revealed that the AUY922-loaded micelle significantly suppressed tumor growth in comparison to the free AUY922, or control groups using tumor-bearing NOD-SCID mice. Moreover, biochemical index and histological analysis revealed synthesized micelle does not show any significant cytotoxicity to the selected major organs. Overall, a synthesized micelle is the best carrier for AUY922 to enhance the therapeutic efficiency of brain cancer.

There is an urgent need for materials that can efficiently generate reactive oxygen species (ROS) and be used in photodynamic therapy (PDT) as two-photon imaging contrast probes. In this study, graphene quantum dots (GQDs) were subjected to amino group functionalization and nitrogen doping (amino-N-GQDs) via annealing and hydrothermal ammonia autoclave treatments. The synthesized dots could serve as a photosensitizer in PDT and generate more ROS than conventional GQDs under 60-s low-energy (fixed output power: 0.07 W·cm⁻²) excitation exerted by a 670-nm continuous-wave laser. The generated ROS were used to completely eliminate a multidrug-resistant strain of methicillin-resistant Staphylococcus aureus (MRSA), a Gram-positive bacterium. Compared with conventional GQDs, the amino-N-GQDs had superior optical properties, including stronger absorption, higher quantum yield (0.34), stronger luminescence, and high stability under exposure. The high photostability and intrinsic luminescence of amino-N-GQDs contribute to their suitability as contrast probes for use in biomedical imaging, in addition to their bacteria tracking and localization abilities. Herein, the dual-modality amino-N-GQDs in PDT easily eliminated multidrug-resistant bacteria, ultimately revealing their potential for use in future clinical applications.