Targeted Nanotheransotics: Integration of Preclinical MRI and CT in the Molecular Imaging and Therapy of Advanced Diseases.

The integration of preclinical magnetic resonance imaging (MRI) and computed tomography (CT) methods has significantly enhanced the area of therapy and imaging of targeted nanomedicine. Nanotheranostics, which make use of nanoparticles, are a significant advancement in MRI and CT imaging. In addition to giving high-resolution anatomical features and functional information simultaneously, these multifunctional agents improve contrast when used. In addition to enabling early disease detection, precise localization, and personalised therapy monitoring, they also enable early disease detection. Fusion of MRI and CT enables precise in vivo tracking of drug-loaded nanoparticles. MRI, which provides real-time monitoring of nanoparticle distribution, accumulation, and release at the cellular and tissue levels, can be used to assess the efficacy of drug delivery systems. The precise localization of nanoparticles within the body is achievable through the use of CT imaging. This technique enhances the capabilities of MRI by providing high-resolution anatomical information. CT also allows for quantitative measurements of nanoparticle concentration, which is essential for evaluating the pharmacokinetics and biodistribution of nanomedicine. In this article, we emphasize the integration of preclinical MRI and CT into molecular imaging and therapy for advanced diseases.

Redox-Sensitive Poly(lactic-co-glycolic acid) Nanoparticles of Palbociclib: Development, Ultrasound/Photoacoustic Imaging, and Smart Breast Cancer Therapy.

Breast cancer is one of the leading causes of mortality in women globally. The efficacy of breast cancer treatments, notably chemotherapy, is hampered by inadequate localized delivery of anticancer agents to the tumor site, resulting in compromised efficacy and increased systemic toxicity. In this study, we have developed redox-sensitive poly(lactic-co-glycolic acid) (PLGA) nanoparticles for the smart delivery of palbociclib (PLB) to breast cancer. The particle size of formulated PLB@PLGA-NPs (nonredox-sensitive) and RS-PLB@PLGA-NPs (redox-sensitive) NPs were 187.1 ± 1.8 nm and 193.7 ± 1.5 nm, respectively. The zeta potentials of nonredox-sensitive and redox-sensitive NPs were +24.99 ± 2.67 mV and +9.095 ± 1.87 mV, respectively. The developed NPs were characterized for morphological and various physicochemical parameters such as SEM, TEM, XRD, DSC, TGA, XPS, etc. The % entrapment efficiency of PLB@PLGA-NPs and RS-PLB@PLGA-NPs was found to be 85.48 ± 1.29% and 87.72 ± 1.55%, respectively. RS-PLB@PLGA-NPs displayed a rapid drug release at acidic pH and a higher GSH concentration compared to PLB@PLGA-NPs. The cytotoxicity assay in MCF-7 cells suggested that PLB@PLGA-NPs and RS-PLB@PLGA-NPs were 5.24-fold and 14.53-fold higher cytotoxic compared to the free PLB, respectively. Further, the cellular uptake study demonstrated that redox-sensitive NPs had significantly higher cellular uptake compared to nonredox-sensitive NPs and free Coumarin 6 dye. Additionally, AO/EtBr assay and reactive oxygen species analysis confirmed the superior activity of RS-PLB@PLGA-NPs over PLB@PLGA-NPs and free PLB. In vivo anticancer activity in dimethyl-benz(a)anthracene-induced breast cancer rats depicted that RS-PLB@PLGA-NPs was highly effective in reducing the tumor size, hypoxic tumor, and tumor vascularity compared to PLB@PLGA-NPs and free PLB. Further, hemocompatibility study reveals that the developed NPs were nonhemolytic to human blood. Moreover, an in vivo histopathology study confirmed that both nanoparticles were safe and nontoxic to the vital organs.

Anti-Parkinson potential of hesperetin nanoparticles: in vivo and in silico investigations.

Parkinson's disease (PD) is characterised by the gradual demise of dopaminergic neurons. In recent years, there has been significant interest in herbal treatments. In this study, hesperetin nanoparticles (HTN) were developed and compared their anti-PD potential with hesperetin (HT) on rotenone induced PD rats. Molecular docking was also performed to evaluate the binding affinity of hesperetin on pathological protein, i.e. D2 dopamine receptors (DR2), using Auto Dock Vina tools. The results showed a higher binding relationship of HTN on dopamine receptors (-7.2 kcal/mol) compared to L-dopa (-6.4 kcal/mol), supporting their potential as drug candidates for PD therapy. HTN was effectively synthesised using the fabrication technique and characterised by zeta potential and SEM analysis. HTN had favourable characteristics, including a size of 249.8 ± 14.9 nm and a Z-potential of -32.9 mV. After being administered orally, HTN demonstrated a notable anti-Parkinsonian effects, indicated by the significant improvement in motor function as assessed by the rota rod test (p < .001***), pole test (p < .001***), stair test (p < .01**), wood walk test (p < .01**) and an increase in substantia nigra (SN) antioxidant levels, CAT (p < .001***), SOD (p < .001***), GSH (p < .01**). Additionally, HTN led to increased dopamine levels (p < .01**) and a decrease in the oxidant system, MDA levels (p < .01**). Furthermore, histopathological examination revealed decreased SN neuronal necrosis in diseased animals treated with HTN compared to those treated with HT in a rat model of Parkinson's disease. Therefore, HTN can be regarded as a viable platform for efficient therapy of PD.