The conjugation of rhodamine B enables carrier-free mitochondrial delivery of functional proteins

The development of protein-based therapeutics faces many challenges, for example, carrier-dependence, safety concerns, endocytosis-dependence, and uncertain in vivo therapeutic outcomes. Small molecules are rarely used for intracellular organelle-targeting and disease tissue-specific carrier-independent delivery of therapeutic proteins. Here, we report that rhodamine B, after modification with proteins, is able to guide carrier-free delivery into mitochondria and tissue-dependent distributions of functional proteins through organic cation transporters (OCTs). The enrichment of the modified catalase in the cancer tissue efficiently suppresses xenograft human lung tumor in mice. This carrier-free delivery platform of proteins may emerge as a simple yet powerful approach for cancer treatment.