RESUMEN
The specific in situ generation and activation of therapeutic agents with high spatiotemporal precision is expected to revolutionize cancer treatment. Here, we develop an intelligent nanoplatform (termed as NP-Cu), which is constructed by assembling photosensitizer chlorin e6 (Ce6), hypoxia-responsive prodrug banoxantrone (AQ4N) with clickable dibenzocyclooctyne (DIBO) functionalized lysine (D-K), and cyclen-Cu2+ complex, for improving combination anticancer therapy. Cyclen-Cu2+ complex-induced photodynamic therapy (PDT) quenching in NP-Cu can be effectively and selectively activated by tumor-overproduced hydrogen sulfide (H2S). More importantly, the reaction of endogenous H2S with Cu2+ can generate photothermal agent copper sulfide (CuS) for photothermal therapy (PTT). Furthermore, with the activation of PTT and PDT, intracellular hypoxic stress is amplified to trigger AQ4N-associated chemodynamic therapy (CDT), leading to light-enhanced cascade therapy of PDT, PTT and CDT. Therefore, we present a simple and practical strategy for developing pathological stimuli responsive combination therapy, which has the potential of advancing precision cancer medicine.
Asunto(s)
Neoplasias del Colon , Ciclamas , Nanopartículas , Fotoquimioterapia , Línea Celular Tumoral , Neoplasias del Colon/tratamiento farmacológico , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , FototerapiaRESUMEN
OBJECTIVE: To investigate the relationship between serum anti-C1q antibody levels and renal pathological characteristics in lupus nephritis as well as the prognostic significance of serum anti-C1q antibody. METHODS: Seventy-three patients with biopsy-proven lupus nephritis were enrolled. Anti-C1q antibody was measured in serum samples taken within 7 days before renal biopsy and remeasured at the end of the first and the third month after treatment. All patients were followed at least once a month for 3 months. A cross-sectional study analyzed the relationship between serum anti-C1q antibody levels and renal histopathology and nephritic activity, while a longitudinal study evaluated the prognostic significance of anti-C1q antibody levels in lupus nephritis. RESULTS: Fifty-eight of 73 patients (79.5%) were reported as having positive baseline serum anti-C1q antibody, with a mean level of 95.3 (+/- 55.2) U/ml. Significant differences were found in serum anti-C1q antibody levels between each World Health Organization (WHO) classification of lupus nephritis. The serum anti-C1q antibody level of WHO class IV was the highest. Serum anti-C1q antibody was positively correlated with the active and chronic indices in renal pathology. Patients with persistent high levels or increased titers of serum anti-C1q antibody tended to develop delayed remission in nephropathy. Serum anti-C1q antibody levels before and after treatment were relevant to renal remission, but serum anti-C1q antibody at the end of the third month after treatment was a stronger predictor for the prognosis after adjustment in the Cox's proportional hazards regression model. CONCLUSION: Serum anti-C1q antibody is a valuable noninvasive biological marker for evaluation of renal involvement and lupus prognosis.