Sequentially responsive size reduction and drug release of core-satellite nanoparticles to enhance tumor penetration and effective tumor suppression

Poor tumor accumulation remains a serious challenge for nanomedicines to achieve ideal antitumor outcomes.The different size preferences for systematic circulation,tumor retention and deep permeation have attracted great attention when designing antineoplastic nano-delivery system.Herein,we developed a nano-system which can shrink its size in tumor microenvironment to achieve better tumor retention and penetration.In this work,the cationic bovine serum albumin-protected,doxorubicin-loaded gold nanoclusters(CAuNC-DOX)and amino-functionalized mesoporous silica nanoparticles(MSN)are connected by Fe^(2+)and are further coated with hyaluronic acid(HA)to obtain a core-satellite MSN-Fe-CAuNCDOX@HA nano system(MFADH).When reaching the tumor site,the HA shell,which endows the system with both good biocompatibility and preferable tumor targeting ability,was disintegrated,followed by acid-stimulated release of small-sized pharmacological unit—CAuNC-DOX for further tumor penetration.As demonstrated in both in vitro and in vivo results,MFADH showed excellent antitumor effect,providing a proof of concept for the feasibility of shrinkable nanoplatforms in tumor treatment.