An in vivo click strategy to overcome Circulation/Excretion dilemma in NanoMedicines – ClickNanoClear

Nanoparticles hold great promise for many applications ranging from in vitro diagnostic assays to in vivo imaging and drug delivery. The development of metallic, fluorescent, or contrast imaging nanoparticles (NPs), possessing distinct and unique optical and electronic properties have progressed dramatically. However, the optimization of the ADME (Absorption, Distribution, Metabolism and Excretion) profiles allowing NPs to display broad or highly restricted distribution, to control their circulation time and in particular their clearance from the organism, once they have accomplish their function, is particularly difficult. Indeed it has been widely shown that even well designed NPs tend to accumulate in diverse healthy organs after systemic administration. Today, fine-tuning NPs to reach the exact ADME profile remains a serious issue that often hampers translation of experimental data into nanomedical clinical practice.
Reconciling biodistribution suitable for therapeutic or in vivo imaging purposes with rapid excretion is a difficult task as these two characteristics are somehow antagonist. For example, significant efforts have recently been performed to limit NPs long-term accumulation leading to the development of smaller QDots and AuNPs with efficient renal clearance. However, designing smaller NPs with rapid clearance kinetic display considerably reduced circulation time in the bloodstream, limiting their access into the target site, and thus their potential for biomedical applications.
To address this issue, and control in vivo NPs clearance we thought to investigate the opportunity offered by in vivo click chemistry. Our idea is to engineer onto NPs azide groups that would act as safety pins allowing NP elimination from the body via in vivo click reaction with a clearing agent bearing a strained alkyne. This strategy offers an innovative approach to control elimination of circulating NPs by triggering their clearance from the organism as a result of in vivo biorthogonal click reaction.