"Three-birds with one stone" self-assembled carrier-free drug delivery system for efficient inhibition of breast cancer growth and metastasis.

Metastasis is one of the leading causes of cancer-related death. Inhibition of cancer growth and metastasis are equally important for cancer treatment. The current widely used nanocarrier-based drug delivery strategies for cancer therapy suffer from complex preparation processes, poor loading capacity, poor controllability and unknown toxicity. In this context, present work developed a novel "three-birds with one stone" self-assembled carrier-free drug delivery system, named Ir-Gem@Cap, for efficient inhibition of breast cancer growth and metastasis. The carrier-free drug-drug conjugate M-Ir-Gem was initially developed by conjugating the hydrophilic drug gemcitabine and the hydrophobic photosensitizer (iridium(III) complex) through a alkyl ester group. The obtained M-Ir-Gem was then used for the delivery of capsaicin to obtain a "three-birds with one stone" drug delivery system Ir-Gem@Cap. After Ir-Gem@Cap enters the cancer cell, the ester bond would be hydrolyzed to release gemcitabine, iridium(III) complex photosensitizer and capsaicin, which can be used for chemotherapy, photodynamic therapy, and inhibition of the formation of circulating tumor cell clusters, respectively, thus effectively inhibiting tumor growth and metastasis. In vivo and in vitro experiment results indicated that Ir-Gem@Cap can effectively inhibit breast cancer growth and lung metastasis. This work not only serves as a proof-of-concept for the fabrication of a carrier-free drug delivery system but also offers a promising tumor therapeutic strategy for limiting tumor progression and metastasis.