T cell force-responsive delivery of anticancer drugs using mesoporous silica microparticles

Abstract

T cell-based cancer immunotherapy has achieved great success in the clinic; however, only a small fraction of patients respond to this therapy. Strategies to specifically and safely augment anticancer activity through controlled delivery of T cell supporting factors or drugs for combination therapy remain of high interest. Here, we devised a T cell force-responsive system for selective delivery of anticancer drugs using a mesoporous silica microparticle capped with a DNA force sensor. Upon T cell receptor (TCR) triggering, T cells exerted synaptic forces, a unique biophysical stimulus, to rupture the force-sensitive DNA gatekeepers on the mesopores leading to rapid drug release. Our results demonstrated that this cellular force-responsive system specifically released anticancer drugs in a T cell force-dependent manner and significantly enhanced cancer cell killing in vitro and in vivo. This work opens a new horizon toward designing next-generation drug delivery systems in response to signaling-specific cellular forces.