Full-route advances via biomimetic and biodegradable ultrasmall-in-nano architectures with radiation-photo synergy

Abstract

The overall therapeutic output is significantly affected by the route of nanomedicines in vivo, including the successive steps of delivery, exogenous excitation, and final metabolism, thus requiring the elaborate composition and structure of nanomedicines. To develop nanomedicines with the full-route advances, we have designed and architected the biomimetic and biodegradable ultrasmall-in-nano particles (UiNP, 80 nm) with the radiation-photo synergy for the first time, by utilizing cancer cell membrane (CCM) nanovehicles to camouflage multiple ultrasmall particles (UP6, 6 nm) composed of Chlorin e6 (Ce6) and hafnium (Hf) clusters via the covalent coordination. The UiNP with the camouflage effect, homotypic adhesion and suitable size can obtain 4-fold blood circulation half-live that of UP6 and 2.5-fold accumulation level that of nanoparticle (NP180, 180 nm), achieving delivery advance. Moreover, the UiNP not only exhibit a dual-modal X-ray therapy with radio-radiodynamic effect via energy transfer but also afford a dual-modal phototherapy with photodynamic-photothermal effect by adjusting the radiative-nonradiative transition of Ce6 within the confined space, thus balancing the killing efficacy and the penetration depth for therapeutic advance. Furthermore, benefiting from the ultrasmall size and intrinsic biodegradability of UP6 and CCM camouflage, the UiNP are less accumulated in reticuloendothelial organs than NP180 and thereby rapid metabolize via urine and feces, exerting the metabolic advance. Therefore, such novel UiNP architectures with full-route advances are much superior to the conventional agents, which can provide some insights for developing new types of ultrasmall-in-nano agents.