Surfactant protein D inhibits lipid-laden foamy macrophages and lung inflammation in chronic obstructive pulmonary disease.

Increased levels of surfactant protein D (SP-D) and lipid-laden foamy macrophages (FMs) are frequently found under oxidative stress conditions and/or in patients with chronic obstructive pulmonary disease (COPD) who are also chronically exposed to cigarette smoke (CS). However, the roles and molecular mechanisms of SP-D and FMs in COPD have not yet been determined. In this study, increased levels of SP-D were found in the bronchoalveolar lavage fluid (BALF) and sera of ozone- and CS-exposed mice. Furthermore, SP-D-knockout mice showed increased lipid-laden FMs and airway inflammation caused by ozone and CS exposure, similar to that exhibited by our study cohort of chronic smokers and COPD patients. We also showed that an exogenous recombinant fragment of human SP-D (rfhSP-D) prevented the formation of oxidized low-density lipoprotein (oxLDL)-induced FMs in vitro and reversed the airway inflammation and emphysematous changes caused by oxidative stress and CS exposure in vivo. SP-D upregulated bone marrow-derived macrophage (BMDM) expression of genes involved in countering the oxidative stress and lipid metabolism perturbations induced by CS and oxLDL. Our study demonstrates the crucial roles of SP-D in the lipid homeostasis of dysfunctional alveolar macrophages caused by ozone and CS exposure in experimental mouse emphysema, which may provide a novel opportunity for the clinical application of SP-D in patients with COPD.

Two-Photon Photoexcited Photodynamic Therapy with Water-Soluble Fullerenol Serving as the Highly Effective Two-Photon Photosensitizer Against Multidrug-Resistant Bacteria.

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 C60(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 C60(OH)30 fullerenol to act as a promising two-photon photosensitizer proceeding with PDT to easily eliminate MDR species.

Amino-Functionalized Nitrogen-Doped Graphene Quantum Dots for Efficient Enhancement of Two-Photon-Excitation Photodynamic Therapy: Functionalized Nitrogen as a Bactericidal and Contrast Agent.

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.

Water-Soluble Fullerenol with Hydroxyl Group Dependence for Efficient Two-Photon Excited Photodynamic Inactivation of Infectious Microbes.

We successfully prepared water-soluble fullerenol [C60(OH)46] that exhibited a high singlet oxygen quantum yield and efficiently generated reactive oxygen species. Additionally, the water-soluble C60(OH)46 with a higher composition of exposed hydroxyl groups had superior two-photon stability and characteristics compared with that with a lower composition of such groups. Therefore, the prepared fullerenol can be an effective two-photon photosensitizer. The water-soluble C60(OH)46 had favorable two-photon properties. During two-photon photodynamic therapy, the water-soluble C60(OH)46 had substantial antimicrobial activity against Escherichia coli at an ultralow-energy level of 211.2 nJ pixel-1 with 800 scans and a photoexcited wavelength of 760 nm.

Amino-Functionalized Nitrogen-Doped Graphene-Quantum-Dot-Based Nanomaterials with Nitrogen and Amino-Functionalized Group Content Dependence for Highly Efficient Two-Photon Bioimaging.

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 (AbEGFR) was used for labeling to increase specificity. Two-photon imaging (TPI) of amino-N-GQD (6.2%)-polymer-AbEGFR-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-AbEGFR-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.