The current interest for platinum N-heterocyclic carbene complexes in cancer research stems from their impressive toxicity reported against a range of different human cancer cells. To date, the demonstration of their in vivo efficacy relative to that of established platinum-based drugs has not been specifically addressed. Here, we introduce an innovative approach to increase the NHC-Pt complex potency whereby multiple NHC-Pt(II) complexes are coordinated along a polyethylenimine polymer (PEI) chain. We show that such NHC-Pt(II)-PEI conjugates induce human cancer cell death in vitro and in vivo in a xenograft mouse model with no observable side effects in contrast to oxaliplatin. Additional studies indicate nucleus and mitochondria targeting and suggest various mechanisms of action compared to classical platinum-based anticancer drugs.

Background:The activation of CD40 is essential for the development of humoral and cellular immune responses. Results: CD40 dimerizes through the extracellular region via the CRD1, and recombinant CRD1 potentiates CD40L activity. Conclusion: CD40-CRD1 participates to dimerization and is required for efficient receptor expression. Significance: CD40 self-assembly modulates signaling, possibly by maintaining the receptor in a quiescent state.