posted on 2024-05-16, 02:03authored byPeng Xie, Qiao Jin, Lingpu Zhang, Hanchen Zhang, Nicolás Montesdeoca, Johannes Karges, Haihua Xiao, Xinzhan Mao, Haiqin Song, Kun Shang
Tumor metastases and reoccurrence are considered the
leading causes
of cancer-associated deaths. As an emerging therapeutic method, increasing
research efforts have been devoted to immunogenic cell death (ICD)-inducing
compounds to solve the challenge. The clinically approved chemotherapeutic
Pt complexes are not or are only poorly able to trigger ICD. Herein,
the axial functionalization of the Pt(II) complex cisplatin with perfluorocarbon
chains into ICD-inducing Pt(IV) prodrugs is reported. Strikingly,
while the Pt(II) complex as well as the perfluorocarbon ligands did
not induce ICD, the Pt(IV) prodrug demonstrated unexpectantly the
induction of ICD through accumulation in the endoplasmic reticulum
and generation of reactive oxygen species in this organelle. To enhance
the pharmacological properties, the compound was encapsulated with
human serum albumin into nanoparticles. While selectively accumulating
in the tumorous tissue, the nanoparticles demonstrated a strong tumor
growth inhibitory effect against osteosarcoma inside a mouse model. In vivo tumor vaccine analysis also demonstrated the ability
of Pt(IV) to be an ideal ICD inducer. Overall, this study reports
on axially perfluorocarbon chain-modified Pt(IV) complexes for ICD
induction and chemoimmunotherapy in osteosarcoma.