Aptamer-Gold Nanocluster Coupling–Decoupling for Efficient Cancer Theranostics

Abstract

Despite noteworthy progress in biomedical applications, aptamers encounter substantial obstacles in the realm of in vivo cancer theranostics, primarily due to the susceptibility of native aptamers to degradation and the compromised affinity of engineered aptamers. Herein, an aptamer/gold nanoclusters (Apt-M/AuNCs)-based system, featuring a facile noncovalent coupling and biomarker-responsive decoupling mechanism, is developed for activated tumor imaging and integrated gene-chemotherapy. Specifically, we employed the tumor biomarker legumain as a model imaging switch and manganese superoxide dismutase (MnSOD) mRNA as a therapeutic target, respectively, facilitated by tailored peptides (bioligands of AuNCs) and the aptamer AS1411-antisense mRNA (Apt-M). Compared to monomeric Apt-M, the Apt-M/AuNCs system exhibited significant improvements in both stability and binding affinity, subsequently translating to notable enhancements in imaging contrast and therapeutic efficacy. Endowed with remarkable biostability, affinity, and specificity, our work offers a facile route for efficient aptamer functionalization and subsequently superior theranostics performance, thereby holding great potential for broadening the application of aptamers into an ever-growing array of research fields.