The therapeutic potential of the Pat-HBc/RSG&ZnPcS4 nanocomplex was rigorously evaluated in obese (Ob/Ob) mice over a two-week treatment regimen involving two cycles of intravenous administration followed by abdominal laser irradiation. The study demonstrated significant anti-obesity effects, robust metabolic improvements, and an acceptable safety profile, supporting its translational viability.
Mice treated with Pat-HBc/RSG&ZnPcS4 exhibited a sustained and pronounced reduction in body weight—exceeding 10% after two cycles—compared to minimal changes in control, RSG-only, ZnPcS4-only, or combination groups without targeting. Daily monitoring revealed no significant differences in food intake across groups, confirming that weight loss was due to increased energy expenditure rather than appetite suppression. Visual inspection showed visibly leaner body contours, particularly in the abdominal region, with reduced fat pad mass confirmed at necropsy.
Photoacoustic imaging provided real-time, non-invasive assessment of treatment progression. Three-dimensional scans revealed a progressive decrease in adipose volume in iWAT, pWAT, and mWAT, with the most dramatic reduction observed in mWAT and pWAT—regions with high vascular density. Concurrently, vascular length density significantly increased, indicating active angiogenesis driven by RSG and facilitated by PDT-induced hypoxia. These findings were corroborated by histological analysis, which showed marked shrinkage of adipocytes and reduced lipid droplet size in all WAT depots, especially in pWAT and mWAT.
Metabolic health improved markedly. Fasting serum glucose and insulin levels declined, resulting in a lower insulin resistance index (IRI), suggesting enhanced insulin sensitivity. Oral glucose tolerance tests confirmed improved glucose clearance, further validating metabolic recovery. Hepatic steatosis was alleviated, as evidenced by reduced liver triglyceride content and less lipid accumulation on H&E staining, likely due to RSG’s ability to improve systemic insulin sensitivity and reduce lipotoxicity.
Histopathological evaluation of major organs—including liver, kidney, heart, lung, and spleen—revealed no signs of toxicity. Hematoxylin and eosin (H&E) staining showed normal tissue architecture with no inflammatory infiltrates, necrosis, or fibrosis. Serum biomarkers for hepatic function (ALT, AST), renal function (urea, creatinine), and cardiac function (CK, CK-MB, LDH) remained within normal ranges, indicating no organ damage. Notably, even baseline markers of oxidative stress (MDA, 4-HNE, 8-OHdG) were elevated in the Pat-HBc/RSG&ZnPcS4 group post-treatment, but this was not accompanied by clinical toxicity—suggesting controlled, localized oxidative stress confined to adipose tissue.
Immunogenicity was assessed in a separate cohort of mice sensitized with ovalbumin, HBc, or Pat-HBc. While wild-type HBc elicited strong IgG and Th2 responses (elevated IL-4), Pat-HBc induced significantly lower immunoglobulin levels and cytokine production, indicating that the insertion of the Pat peptide into the MIR region effectively masked immunogenic epitopes.MUC5AC Antibody In stock However, repeated dosing still triggered a measurable immune response, highlighting a need for future modifications such as PEGylation or use of protein orthologues to further reduce immunogenicity.Csk Antibody manufacturer
In conclusion, the Pat-HBc/RSG&ZnPcS4 complex demonstrates potent, targeted anti-obesity efficacy with favorable safety and tolerability in vivo.PMID:35217923 Its ability to induce durable fat loss, enhance metabolic function, and maintain organ integrity—while minimizing systemic toxicity—positions it as a promising candidate for clinical development. The integration of photoacoustic imaging for treatment guidance further enhances precision, enabling personalized therapy. Future work will focus on optimizing biocompatibility and long-term safety to advance this strategy toward human application.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com