Gold nanoclusters (AuNCs) have great potential to enhance tumor radiotherapy. However, their tumor accumulation efficiency is relatively low due to their ultrasmall size. In this study, an acid-responsive tumor targeting strategy is proposed by introducing l-cystine onto glutathione-coated AuNCs (l-Cys/GSH@AuNCs). l-Cys/GSH@AuNCs are able to swiftly respond to acid conditions to assembly into large clusters and aggregate in lysosomes upon internalization by tumor cells, leading to increased accumulation in cancer cells. Moreover, metal radioisotope 89Zr and 68Ga could be doped into AuNCs with high efficiency and stability. PET imaging of tumor-bearing mice reveals that radiolabeled l-Cys/GSH@AuNCs are primarily eliminated via the renal system but could respond to tumor acid microenvironment to accumulate in tumor high efficiently and remain in tumors for a long time period. As a result, radiotherapy in combination with l-Cys/GSH@AuNCs completely suppresses tumor growth. Our study paves a way for AuNCs to enhance tumor radiotherapy.
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Jiang et al. (2024) studied this question.
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