Quantitative imaging of the sub-organ distributions of nanomaterials in biological tissues via laser ablation inductively coupled plasma mass spectrometry.

Nanomaterials have been employed in many biomedical applications, and their distributions in biological systems can provide an understanding of their behavior in vivo. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) can be used to determine the distributions of metal-based NMs in biological systems. However, LA-ICP-MS has not commonly been used to quantitatively measure the cell-specific or sub-organ distributions of nanomaterials in tissues. Here, we describe a new platform that uses spiked gelatin standards with control tissues on top to obtain an almost perfect tissue mimic for quantitative imaging purposes. In our approach, gelatin is spiked with both nanomaterial standards and an internal standard to improve quantitation and image quality. The value of the developed approach is illustrated by determining the sub-organ distributions of different metal-based and metal-tagged polymeric nanomaterials in mice organs. The LA-ICP-MS images reveal that the chemical and physical properties of the nanomaterials cause them to distribute in quantitatively different extents in spleens, kidneys, and tumors, providing new insight into the fate of nanomaterials in vivo. Furthermore, we demonstrate that this approach enables quantitative co-localization of nanomaterials and their cargo. We envision this method being a valuable tool in the development of nanomaterial drug delivery systems.

Synergistic Treatment of Multidrug-Resistant Bacterial Biofilms Using Silver Nanoclusters Incorporated into Biodegradable Nanoemulsions.

Multidrug resistance (MDR) in bacteria is a critical global health challenge that is exacerbated by the ability of bacteria to form biofilms. We report a combination therapy for biofilm infections that integrates silver nanoclusters (AgNCs) into polymeric biodegradable nanoemulsions (BNEs) incorporating eugenol. These Ag-BNEs demonstrated synergistic antimicrobial activity between the AgNCs and the BNEs. Microscopy studies demonstrated that Ag-BNEs penetrated the dense biofilm matrix and effectively disrupted the bacterial membrane. The Ag-BNE vehicle also resulted in more effective silver delivery into the biofilm than AgNCs alone. This combinacional system featured disruptionof biofilms by BNEs and enhanced delivery of AgNCs for synergy to provide highly efficient killing of MDR biofilms.

Bioorthogonal nanozymes for breast cancer imaging and therapy.

Bioorthogonal catalysis via transition metal catalysts (TMCs) enables the generation of therapeutics locally through chemical reactions not accessible by biological systems. This localization can enhance the efficacy of anticancer treatment while minimizing off-target effects. The encapsulation of TMCs into nanomaterials generates "nanozymes" to activate imaging and therapeutic agents. Here, we report the use of cationic bioorthogonal nanozymes to create localized "drug factories" for cancer therapy in vivo. These nanozymes remained present at the tumor site at least seven days after a single injection due to the interactions between cationic surface ligands and negatively charged cell membranes and tissue components. The prodrug was then administered systemically, and the nanozymes continuously converted the non-toxic molecules into active drugs locally. This strategy substantially reduced the tumor growth in an aggressive breast cancer model, with significantly reduced liver damage compared to traditional chemotherapy.

LA-ICP-MS and MALDI-MS image registration for correlating nanomaterial biodistributions and their biochemical effects.

Laser ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS) imaging and matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) are complementary methods that measure distributions of elements and biomolecules in tissue sections. Quantitative correlations of the information provided by these two imaging modalities requires that the datasets be registered in the same coordinate system, allowing for pixel-by-pixel comparisons. We describe here a computational workflow written in Python that accomplishes this registration, even for adjacent tissue sections, with accuracies within ±50 µm. The value of this registration process is demonstrated by correlating images of tissue sections from mice injected with gold nanomaterial drug delivery systems. Quantitative correlations of the nanomaterial delivery vehicle, as detected by LA-ICP-MS imaging, with biochemical changes, as detected by MALDI-MSI, provide deeper insight into how nanomaterial delivery systems influence lipid biochemistry in tissues. Moreover, the registration process allows the more precise images associated with LA-ICP-MS imaging to be leveraged to achieve improved segmentation in MALDI-MS images, resulting in the identification of lipids that are most associated with different sub-organ regions in tissues.

Bioassay-Guided Fractionation, Chemical Compositions and Antibacterial Activity of Extracts from Rhizomes of Globba schomburgkii Hook.f.

Bioassay-guided fractionation was conducted on dichloromethane extract from the rhizomes of Globba schomburgkii Hook.f., which have previously been reported as the part with the highest antibacterial activity. 10 fractions and 20 sub-fractions were obtained and evaluated for their potency against various strains of bacteria. The most active sub-fractions were 8 times more effective against Staphylococcus aureus and Micrococcus luteus than the original crude extract. Moreover, two pure compounds, namely petasol and (E)-15,16-dinorlabda-8(17),11-dien-13-one, were successfully isolated and characterized for the first time from this plant species. Untargeted compound analysis of all fractions and sub-fractions was performed by gas chromatography hyphenated with mass spectrometry, leading to positive identification of 167 compounds according to comparison with the mass spectrum and retention index database, 137 of which have never been reported for G. schomburgkii. The correlation between antibacterial activity and composition of each fraction suggests that the bioactive compounds could be 4,8-ß-epoxycaryophyllene, methyl isocostate, (E)-labda-8(17),12-diene-15,16-dial, α-kessyl acetate, zederone, clovanediol, ledene oxide-(I), alantolactone, or 8α,11-elemadiol.

α7-Nicotinic acetylcholine receptor antagonist QND7 suppresses non-small cell lung cancer cell proliferation and migration via inhibition of Akt/mTOR signaling.

Lung cancer, one of the most commonly found carcinoma type, has the highest mortality rate in cancer patients worldwide. Therapeutic interventions targeting to lung cancer become remaining the world significant challenge. Recently, the α7-nicotinic acetylcholine receptor (α7-nAChR) was reported to play an important role in the mechanism underlying lung cancer progression, being intriguing drug target for lung cancer therapy. Hence, the top four α7-nAChR antagonists (QND7, PPRD10, PPRD11 and PPRD12) among our previously developed ligands were proceeded to the in vitro anti-cancer evaluations in non-small cell lung cancer (NSCLC) cell lines (H460 and A549). In this study, we found that QND7 exhibited the highest cytotoxic effect and induced cell apoptosis in both cell lines at a level comparable to cisplatin, whereas the PPRD compounds showed much lower cytotoxicity. Low doses of QND7 and PPRD11 were able to suppress H460 and A549 cell proliferation, whereas PPRD10 and PPRD12 were considered ineffective. In an in vitro wound healing assay, QND7-treatment showed the greatest suppression of H460 and A549 cell migration. The variations in the anti-cancer activities of PPRD compounds might be, at least in part of, their non-selective antagonisms to serotonin receptor (5-HT3) and α4ß2-nAChR. Further investigation revealed that QND7 was able to minimize protein kinase B/mammalian target of rapamycin (Akt/mTOR) activity, in correlating to its anti-cancer effects. These findings warrant QND7 for further preclinical evaluation and demonstrate the potential of α7-nAChR as cancer drug target.

Volatile Chemical Composition, Antibacterial and Antifungal Activities of Extracts from Different Parts of Globba schomburgkii Hook.f.

Globba schomburgkii Hook.f. is an ornamental plant that has recently found increasing demand as cut flowers, hence generating a significant number of by-products from different parts of the plant. To investigate the further applications of these by-products, twelve crude extracts from rhizomes, stalks, leaves, and flowers were prepared by serial exhaustive extraction. The volatile composition of these extracts was analyzed by GC/MS; a total of 89 compounds were identified, most of which were sesquiterpenes as well as some labdane-type diterpenes. The antimicrobial activities of these extracts were evaluated, revealing a correlation between the terpenoid content and antibacterial activities. Notably, the dichloromethane extracts of rhizomes and flowers, which contained the highest amount of terpenoids (e. g., α-gurjunene, guaia-9,11-diene, γ-bicyclohomofarnesal, ß-caryophyllene, and caryophyllene oxide), displayed the most prominent antibacterial activities. This work demonstrates the potential use of the crude extracts from G. schomburgkii as natural antibacterial ingredients for pharmaceutical and other applications.