Self-Assembly of Intelligent Nanoplatform for Endogenous H2S-Triggered Multimodal Cascade Therapy of Colon Cancer.

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.

Correlation between serum anti-C1q antibody levels and renal pathological characteristics and prognostic significance of anti-C1q antibody in lupus nephritis.

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.