Background/Objectives: An inhibitor of small Rho GTPase Cdc42, CASIN, has been shown to reduce cancer cell proliferation, migration, and invasion, yet it has several limitations, including rapid drug elimination and low bioavailability, which prevents its systemic administration. In this study, we designed and characterized a nanoparticle-based delivery system for CASIN encapsulated within poly(lactide-co-glycolide)-block-poly(ethylene glycol)-carboxylic acid endcap nanoparticles (PLGA-PEG-COOH NPs) for targeted inhibition of Cdc42 activity in colon cancer. Methods: We applied DLS, TEM, and UV–vis spectroscopy methods to characterize the size, polydispersity index, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release of the synthesized nanoparticles. The CCK-8 cell viability test was used to study colorectal cancer cell growth in vitro. Results: We showed that CASIN-PLGA-PEG-COOH NPs were smooth, spherical, and had a particle size of 86 ± 1 nm, with an encapsulation efficiency of 66 ± 5% and a drug-loading capacity of 5 ± 1%. CASIN was gradually released from NPs, reaching its peak after 24 h, and could effectively inhibit the proliferation of HT-29 (IC50 = 19.55 µM), SW620 (IC50 = 9.33 µM), and HCT116 (IC50 = 10.45 µM) cells in concentrations ranging between 0.025–0.375 mg/mL. CASIN-PLGA-PEG-COOH NPs demonstrated low hemolytic activity with a hemolytic ratio of less than 1% for all tested concentrations. Conclusion: CASIN-PLGA-PEG-COOH NPs have high encapsulation efficiency, sustained drug release, good hemocompatibility, and antitumor activity in vitro. Our results suggest that PLGA-PEG-COOH nanoparticles loaded with CASIN show potential as a targeted treatment for colorectal cancer and could be recommended for further in vivo evaluation.

Dihydroquercetin (DHQ), a powerful antioxidant and regulator of cellular metabolism, was proposed for therapy of neurodegenerative disorders. Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS) are serious neurodegenerative disorders with oxidative stress as an overlapping feature and unmet therapeutic needs. To date, few studies have explored the efficacy of DHQ in animal models of genetically driven neurodegeneration. Here, APPswe/PS1dE9 (APP/PS1) mice and their wild-type (WT) littermates were orally administered DHQ (0.6 mg/kg/day) for four months, starting at eight months of age. At the age of 12 months, behavioral evaluation was performed, followed by brain staining with Congo red for amyloid plaque scoring and immunohistochemical analysis of GFAP-positive cells for the assessment of astrogliosis. Malondialdehyde (MDA) levels in the prefrontal cortex were studied as a marker of oxidative stress. Second, two-month-old FUS[1-359]-Tg mice, which recapitulate the hallmarks of ALS, received DHQ for 1.5 months and were investigated for general physiological parameters, the onset of paralysis, motor functions, and density of motor neurons in the spinal cord. DHQ-treated APPswe/PS1dE9 mutants displayed a decrease in amyloid plaque density of small size (≤100 μm) in the cortex and thalamus, had normalized MDA levels, improved conditioned taste aversion and Y-maze learning, and ameliorated anxiety measures, whereas their hippocampus-dependent step-down and pellet displacement performance remained impaired. In the second study, DHQ-treated FUS[1-359]-Tg mice showed rescued density of spinal cord neurons, normalized liquid and diet intake, and improved coat state, while the onset of paralysis and motor scores were not significantly ameliorated. Thus, chronic administration of low doses of DHQ exerted neuroprotective effects in both AD and ALS genetic models, which partially translated to reduced manifestations of these diseases.