Abstract
Precise delivery of radionuclides and anticancer drugs to tumor tissue is crucial to ensuring drug synergism and optimal therapeutic effects in radionuclide-based combination radio-chemotherapy. However, current codelivery vectors often rely on physical embedment/adsorption to load anticancer drugs, which lacks precise mechanisms for drug loading and release, resulting in unpredictable combination effects. Herein, a macrocyclic-albumin conjugate (MAC) that enables precise loading and controlled release of anticancer drugs is presented. By conjugating multiple macrocyclic hosts (sulfonate azocalix[4]arenes, SAC4A) to albumin molecules, the MAC facilitates the precise loading of anticancer drugs through host-guest interactions and site-specific labeling of radionuclides. Furthermore, the MAC degrades under hypoxic conditions, enabling the release of loaded drugs upon reaching tumor tissues. Through precise loading and targeted delivery of radionuclides and anticancer drugs, MAC achieves efficient cancer diagnosis and combined radio-chemotherapy in breast cancer cell (4T1)-bearing mice. Considering that SAC4A can load many anticancer drugs, MAC may provide a promising platform for effective combination radio-chemotherapy.
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