Rationale: Despite considerable advances, the
reactive oxygen species (ROS)-mediated
cancer treatment suffers from the problems of up-regulation of adaptive
antioxidants in
cancer cells as well as side effects to normal cells. Therefore, development of a new generation of
cancer-specific nanomedicine capable of amplifying oxidative stress would be of great interest for accurate and effective
cancer treatment. Methods: Herein,
transferrin (Tf)-decorated,
dihydroartemisinin (DHA), L-
buthionine-sulfoximine (BSO), and CellROX-loaded liposomal nanoparticles (Tf-DBC NPs) were developed for precise
cancer theranositcs. Tf-DBC NPs could specifically recognize
cancer cells via Tf-Tf receptor binding and be uptaken into the lysosomes of
cancer cells, where Tf-DBC NPs were activated to release Fe(II), DHA, and BSO. ROS was generated by DHA in the presence of Fe(II), and GSH was depleted by BSO to disrupt the redox balance in
cancer cells. Furthermore, CellROX, as a
fluorescent probe for imaging of intracellular oxidative stress, was used to monitor the therapeutic efficacy. Results: The integration of Tf, DHA, and BSO into the acidic pH-responsive
liposomes selectively and effectively killed
cancer cells and prevented the oxidative injury to normal cells. The high oxidative state was visualized at the
tumor site and the amplification of oxidative stress enabled
tumor eradication by Tf-DBC NPs, demonstrating the successful implementation of this novel strategy in vivo. Conclusion: Our study provides a new paradigm for the design of ROS-mediated
therapeutics and offers a promising perspective for precise
cancer treatment.