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Small molecule fluorophores often face challenges such as short blood half-life, limited physicochemical and optical stability, and poor pharmacokinetics. To overcome these limitations, we conjugated the zwitterionic near-infrared fluorophore ZW800-PEG to human serum albumin (HSA), creating HSA-ZW800-PEG. This conjugation notably improves chemical, physical, and optical stability under physiological conditions, addressing issues commonly encountered with small molecules in biological applications. Additionally, the high molecular weight and extinction coefficient of HSA-ZW800-PEG enhances biodistribution and tumor targeting through the enhanced permeability and retention effect. The unique distribution and elimination dynamics, along with the significantly extended blood half-life of HSA-ZW800-PEG, contribute to improved tumor targetability in both subcutaneous and orthotopic xenograft tumor-bearing animal models. This modification not only influences the pharmacokinetic profile, affecting retention time and clearance patterns, but also enhances bioavailability for targeting tissues. Our study guides further development and optimization of targeted imaging agents and drug-delivery systems.
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Neoplasias , Albumina Sérica Humana , Animais , Humanos , Distribuição Tecidual , Neoplasias/diagnóstico por imagem , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos , Corantes Fluorescentes , IonóforosRESUMO
The cost-minimization hypothesis proposes that positive allometry in sexually selected traits can be explained if the proportional energetic maintenance costs of weapons decrease as traits increase in size. Energetic maintenance costs are the costs of maintaining homeostasis. They are slow, persistent energy sinks that are distinct from ephemeral costs of growth. Because some tissues expend more energy on maintenance than others, energetic maintenance costs can be inferred from proportional tissue composition. For example, soft tissues require more energy for maintenance than exoskeleton, so an arthropod claw that is 50% soft tissue and 50% exoskeleton would have higher energetic maintenance costs than one that is 30% soft tissue and 70% exoskeleton. I tested the cost-minimization hypothesis using proportional tissue composition as a proxy for energetic maintenance costs in snapping shrimp (Alpheus heterochaelis and Alpheus estuariensis) and fiddler crabs (Uca pugilator). As predicted, larger weapons comprised proportionally less soft tissue mass and more exoskeleton mass than smaller weapons. Furthermore, I extended cost-minimization to explain trait exaggeration: individuals might exaggerate traits by investing more mass in exoskeleton. As predicted, exoskeleton mass proportional to weapon mass increased as exaggeration increased. These results support and extend the cost-minimization hypothesis to explain positive allometry and weapon exaggeration.
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Artrópodes , Braquiúros , Exoesqueleto Energizado , Animais , Humanos , Fenótipo , Caracteres Sexuais , Comportamento SexualRESUMO
Many crustaceans produce sounds that might be used in communication. However, little is known about sound detection in crustaceans, hindering our understanding of crustacean acoustic communication. Sound detection has been determined only for a few species, and for many species, it is unclear how sound is perceived: as particle motion or sound pressure. Snapping shrimp are amongst the loudest and most pervasive marine sound sources. They produce snaps during interactions with conspecifics, and they also interact with soniferous heterospecifics. If they can hear, then sound could facilitate key behavioral interactions. We measured the auditory sensitivity of the snapping shrimp, Alpheus richardsoni, using auditory evoked potentials in response to a shaker table that generated only particle motion and an underwater speaker that generated both particle motion and sound pressure. Auditory detection was most sensitive between 80 and 100 Hz, and auditory evoked potentials were detected up to 1500 Hz. Snapping shrimp responded to both the shaker table and the underwater speaker, demonstrating that they detect acoustic particle motion. Crushing the statocyst reduced or eliminated hearing sensitivity. We conclude that snapping shrimp detect acoustic particle motion using the statocyst, they might detect conspecifics and heterospecifics, and hearing could facilitate key behavioral interactions.
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Estimulação Acústica , Vias Auditivas/fisiologia , Penaeidae/fisiologia , Som , Testes de Impedância Acústica , Comunicação Animal , Animais , Potenciais Evocados Auditivos , Audição/fisiologia , Movimento (Física) , Limiar Sensorial , Microtomografia por Raio-XRESUMO
Evolutionary theory suggests that individuals should express costly traits at a magnitude that optimizes the trait bearer's cost-benefit difference. Trait expression varies across a species because costs and benefits vary among individuals. For example, if large individuals pay lower costs than small individuals, then larger individuals should reach optimal cost-benefit differences at greater trait magnitudes. Using the cavitation-shooting weapons found in the big claws of male and female snapping shrimp, we test whether size- and sex-dependent expenditures explain scaling and sex differences in weapon size. We found that males and females from three snapping shrimp species (Alpheus heterochaelis, Alpheus angulosus, and Alpheus estuariensis) show patterns consistent with tradeoffs between weapon and abdomen size. For male A. heterochaelis, the species for which we had the greatest statistical power, smaller individuals showed steeper tradeoffs. Our extensive dataset in A. heterochaelis also included data about pairing, breeding season, and egg clutch size. Therefore, we could test for reproductive tradeoffs and benefits in this species. Female A. heterochaelis exhibited tradeoffs between weapon size and egg count, average egg volume, and total egg mass volume. For average egg volume, smaller females exhibited steeper tradeoffs. Furthermore, in males but not females, large weapons were positively correlated with the probability of being paired and the relative size of their pair mates. In conclusion, we identified size-dependent tradeoffs that could underlie reliable scaling of costly traits. Furthermore, weapons are especially beneficial to males and burdensome to females, which could explain why males have larger weapons than females.
From deer antlers to crab claws, weapons are some of the most elaborate and enormous structures in the animal kingdom. Within a species, weapon size generally increases with the size and condition of an individual, and those with larger weapons are usually better at fending off more diminutive competitors. Although it may seem desirable for all individuals to have large weapons, size varies greatly within a species. The 'handicap principle' proposes that the cost of bearing a weapon dictates the variation in weapon size. Smaller or less fit individuals pay more for weapons than larger or fitter animals, so smaller individuals tend to grow smaller weapons. Although popular, only a handful of studies have demonstrated experimental evidence that supports this theory. To test the handicap principle, Dinh and Patek studied a group of crustaceans known as snapping shrimp. Each shrimp has one enlarged claw that it uses as a weapon to fire imploding vapor bubbles at opponents during fights. Larger snapping shrimp have bigger enlarged claws and tend to win more contests. Males also have larger weapons than females, and this sex difference is amplified during the breeding season. Dinh and Patek studied weapon size in several species of snapping shrimp. Measurements showed that after controlling for body size, individuals with larger weapons had smaller abdomens, suggesting there is a tradeoff between weapon size and abdomen size. Furthermore, small males exhibited the steepest tradeoff, in line with the handicap principle. Snapping shrimp also showed sex-specific costs and benefits. After controlling for body size, females with larger weapons produced fewer and smaller eggs, while males with larger weapons were more likely to be paired with females and generally paired with larger females. This suggests that weapons are particularly burdensome to female shrimp and particularly beneficial to males, especially during the breeding season. These findings provide elusive evidence for the handicap principle and extend the theory to explain sex and seasonal differences in the size of snapping shrimp weapons. More broadly, the findings highlight the value of studying both male and female animal weapons when, historically, the focus has been on male weaponry.
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Decápodes , Caracteres Sexuais , Animais , Feminino , Masculino , Evolução Biológica , Estações do AnoRESUMO
Optical tissue phantoms (OTPs) have been extensively applied to the evaluation of imaging systems and surgical training. Due to their human tissue-mimicking characteristics, OTPs can provide accurate optical feedback on the performance of image-guided surgical instruments, simulating the biological sizes and shapes of human organs, and preserving similar haptic responses of original tissues. This review summarizes the essential components of OTPs (i.e., matrix, scattering and absorbing agents, and fluorophores) and the various manufacturing methods currently used to create suitable tissue-mimicking phantoms. As photobleaching is a major challenge in OTP fabrication and its feedback accuracy, phantom photostability and how the photobleaching phenomenon can affect their optical properties are discussed. Consequently, the need for novel photostable OTPs for the quantitative evaluation of surgical imaging devices is emphasized.
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Near-infrared (NIR) cyanine dyes showed enhanced properties for biomedical imaging. A systematic modification within the cyanine skeleton has been made through a facile design and synthetic route for optimal bioimaging. Herein, we report the synthesis of 11 NIR cyanine fluorophores and an investigation of their physicochemical properties, optical characteristics, photostability, and in vivo performance. All synthesized fluorophores absorb and emit within 610-817 nm in various solvents. These dyes also showed high molar extinction coefficients ranging from 27,000 to 270,000 cm-1 M-1, quantum yields 0.01 to 0.33, and molecular brightness 208-79,664 cm-1 M-1 in the tested solvents. Photostability data demonstrate that all tested fluorophores 28, 18, 20, 19, 25, and 24 are more photostable than the FDA-approved indocyanine green. In the biodistribution study, most compounds showed tissue-specific targeting to selectively accumulate in the adrenal glands, lymph nodes, or gallbladder while excreted to the hepatobiliary clearance route. Among the tested, compound 23 showed the best targetability to the bone marrow and lymph nodes. Since the safety of cyanine fluorophores is well established, rationally designed cyanine fluorophores established in the current study will expand an inventory of contrast agents for NIR imaging of not only normal tissues but also cancerous regions originating from these organs/tissues.
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Two of the most pressing challenges facing bioimaging are nonspecific uptake of intravenously administered contrast agents and incomplete elimination of unbound targeted agents from the body. Designing a targeted contrast agent that shows fast clearance from background tissues and eventually the body after complete targeting is key to the success of image-guided interventions. Here, this work describes the development of renally clearable near-infrared contrast agents and their potential use for dual-channel image-guided tumor targeting. cRGD-ZW800-PEG (800 nm channel) and ZW700-PEG (700 nm channel) are able to visualize tumor margins and tumor vasculature simultaneously and respectively. These targeted agents show rapid elimination from the bloodstream, followed by renal clearance, which together significantly lower off-target background signals and potential toxicity. To demonstrate its applicability, this multispectral imaging is performed in various tumor-bearing animal models including lung cancer, pancreatic neuroendocrine tumors, breast, and ovarian cancer.
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Meios de Contraste , Neoplasias Pulmonares , Animais , Imagem Óptica/métodos , Espectroscopia de Luz Próxima ao Infravermelho , Corantes FluorescentesRESUMO
Thirteen red-shifted pentamethine dimethyl and diethylamino tetrahydroxanthylium derivatives have been successfully synthesized via the microwave-assisted approach. The optimized conditions developed in the synthesis provided an excellent yield in expedited reaction time. These newly synthesized dyes show well-defined optical properties resulting from the diverse substitutions at the central meso positions. The majority of the compounds have a maximum wavelength of absorbance within 946-1022 nm with extinction coefficients in the range of 9700-110,680 M-1 cm-1 in various solvents such as MeOH, EtOH, DMSO, DCM, MeCN, and DMF. These fluorophores, to the best of our knowledge, are the first NIR-II small molecules synthesized using microwave chemistry. We also investigated these dyes for their NIR fluorescence imaging capabilities. Diethylamino-substituted compounds and bromination resulted in higher uptake in the adrenal gland compared to dimethylamino fluorophores. In addition, micellar structures of compounds 7 and 15 improved the targetability of the original dyes to the bone marrow, lymph nodes, and nerves. Overall, NIR-II imaging has the potential to visualize biologically targeted tissues in living organisms.
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MHI-I2 (1) and QuatCy-I2 (2) were compared in terms of properties important for early-stage photodynamic therapy preclinical candidates. Thus, experiments were performed to monitor dark cytotoxicities, light/dark cytotoxicity ratios, selectivity of localization in tumors over other organs, and clearance from the plasma.
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BACKGROUND: Due to the deep tissue penetration and reduced scattering, NIR-II fluorescence imaging is advantageous over conventional visible and NIR-I fluorescence imaging for the detection of bone growth, metabolism, metastasis, and other bone-related diseases. METHODS: Bone-targeted heptamethine cyanine fluorophores were synthesized by substituting the meso-carbon with a sulfur atom, resulting in a bathochromic shift and increased fluorescence intensity. The physicochemical, optical, and thermal stability of newly synthesized bone-targeted NIR fluorophores was performed in aqueous solvents. Calcium binding, bone-specific targeting, biodistribution, pharmacokinetics, and 2D and 3D NIR imaging were performed in animal models. RESULTS: The newly synthesized S-substituted heptamethine fluorophores demonstrated a high affinity for hydroxyapatite and calcium phosphate, which improved bone-specific targeting with signal-background ratios > 3.5. Particularly, P800SO3-PEG showed minimum nonspecific uptake, and most unbound molecules were excreted into the urinary bladder. Histological analyses demonstrated that P800SO3-PEG remained stable in the bone for over two weeks and was incorporated into bone matrices. Interestingly, the flexible thiol ethylene glycol linker on P800SO3-PEG induced a promising photothermal effect upon NIR laser irradiation, demonstrating potential theranostic imaging. CONCLUSIONS: P800SO3-PEG shows a high affinity for bone tissues, deeper tissue imaging capabilities, minimum nonspecific uptake in the major organs, and photothermal effect upon laser irradiation, making it optimal for bone-targeted theranostic imaging.
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Sound-sensitive organisms are abundant on coral reefs. Accordingly, experiments suggest that boat noise could elicit adverse effects on coral reef organisms. Yet, there are few data quantifying boat noise prevalence on coral reefs. We use long-term passive acoustic recordings at nine coral reefs and one sandy comparison site in a marine protected area to quantify spatio-temporal variation in boat noise and its effect on the soundscape. Boat noise was most common at reefs with high coral cover and fish density, and temporal patterns reflected patterns of human activity. Boat noise significantly increased low-frequency sound levels at the monitored sites. With boat noise present, the peak frequencies of the natural soundscape shifted from higher frequencies to the lower frequencies frequently used in fish communication. Taken together, the spectral overlap between boat noise and fish communication and the elevated boat detections on reefs with biological densities raises concern for coral reef organisms.