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1.
Adv Sci (Weinh) ; : e2401424, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39231370

RESUMEN

Autodynamic cancer therapy possesses tremendous potential for enhancing therapeutic efficacy by initiating the treatment process autonomously within targeted cells. However, challenges related to biocompatibility and targeted delivery have hindered its clinical translation owing to the induction of adverse effects and cytotoxicity in healthy cells. In this study, a novel approach for auto-initiated dynamic therapy by conjugating zwitterionic near-infrared fluorophores to a cell-penetrating peptide is proposed. This enables efficient cellular uptake and specific targeting of therapy to desired cells while avoiding off-target uptake. The zwitterionic bioconjugate causes cancer-specific toxicity following its internalization into the targeted cells, triggered by specific intracellular conditions in lysosomes. This innovative approach enables selective targeting of lysosomes in malignant cells while minimizing cytotoxic effects on normal cells. By targeting lysosomes, the method overcomes inherent risks and side effects associated with conventional cancer treatments, offering a selective and effective approach to cancer therapy.

2.
Int J Mol Sci ; 25(1)2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38203730

RESUMEN

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.


Asunto(s)
Neoplasias , Albúmina Sérica Humana , Animales , Humanos , Distribución Tisular , Neoplasias/diagnóstico por imagen , Disponibilidad Biológica , Sistemas de Liberación de Medicamentos , Colorantes Fluorescentes , Ionóforos
3.
J Dent Child (Chic) ; 86(2): 93-100, 2019 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-31395114

RESUMEN

Purpose: To determine if there is a positive correlation between increased body mass index (BMI) and dental development in children.
Methods: The records of 500 six- to 13-year-old children were reviewed, and 250 were included in the study. BMI was calculated for each patient. Panoramic radiographs were evaluated, and dental age was estimated using Cameriere's formula. Delta values (dental age, chronological age) were analyzed using the Kruskal-Wallis test. All tests of hypotheses were two-sided at an alpha level of 0.05.
Results: A statistically significant difference in delta was observed among different BMI categories (P <0.001). Larger deltas were observed for obese patients compared to normal weight patients (P = 0.027) and underweight patients (P = 0.012). Prepubertal patients were observed to have larger deltas than pubertal patients (P < 0.001). Differences between sexes were not significant (P = 0.930).
Conclusion: Obese children were more advanced dentally than normal or under-weight children. Older children were more dentally advanced than their chronological age when compared to younger children. As children grew older, the difference between dental age and chronological age decreased.


Asunto(s)
Determinación de la Edad por los Dientes , Obesidad , Adolescente , Índice de Masa Corporal , Peso Corporal , Niño , Humanos , Radiografía Panorámica , Estados Unidos
4.
Artículo en Inglés | MEDLINE | ID: mdl-18280966

RESUMEN

OBJECTIVES: The objective of this study was to determine the relationship between HIV infection and tooth loss. Based on periodontal reports, we hypothesize HIV+ patients experience greater tooth loss than systemically healthy patients. STUDY DESIGN: This was a retrospective cross-sectional chart study involving 193 HIV+ patients and 192 controls matched on age, race, gender, and smoking status. The relationships between tooth loss and age, race, gender, smoking, CD4+ cell count, and viral load were determined. This study used a 2-year follow-up/maintenance period and was conducted during the era of highly active antiretroviral therapy (HAART). RESULTS: Tooth loss between groups was not significantly different at any time point: (1) before dental treatment; (2) after initial periodontal and restorative treatment; and (3) following a 2-year maintenance period. Age, race, and smoking were risk factors for tooth loss. Among HIV+ individuals, CD4+ cell count and viral load did not influence tooth loss. CONCLUSIONS: HIV infection, in the era of HAART, does not appear to be a risk factor for tooth loss. We also did not find any association between tooth loss and indices of HIV disease progression.


Asunto(s)
Atención Dental para Enfermos Crónicos , Infecciones por VIH/complicaciones , Pérdida de Diente/etiología , Adulto , Factores de Edad , Anciano , Análisis de Varianza , Terapia Antirretroviral Altamente Activa/efectos adversos , Recuento de Linfocito CD4 , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Fumar , Xerostomía/inducido químicamente
5.
J Am Chem Soc ; 124(50): 15094-8, 2002 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-12475355

RESUMEN

We report temperature-dependent excited-state lifetime measurements on [Ru(bpy)(2)dppz](2+) in both protic and aprotic solvents. These experiments yield a unifying picture of the excited-state photophysics that accounts for observations in both types of solvent. Our measurements support the notion of bpy-like and phz-like states associated with the dppz ligand and show that the ligand orbital associated with the bright state is similar in size to the corresponding orbital in the (3)MLCT state of [Ru(bpy)(3)](2+). In contrast to the current thinking, the experiments presented here indicate that the light-switch effect is not driven by a state reversal. Rather, they suggest that the dark state is always lowest in energy, even in aprotic solvents, and that the light-switch behavior is the result of a competition between energetic factors that favor the dark state and entropic factors that favor the bright (bpy) state.


Asunto(s)
Compuestos Organometálicos/química , Fenazinas/química , Rutenio/química , Sondas de ADN/química , Cinética , Mediciones Luminiscentes , Fotoquímica , Termodinámica
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