Journal
BIOMATERIALS
Volume 287, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2022.121681
Keywords
Cancer; Retinoic acid; Hybrid prodrug; Self-assembly; Drug self-delivery
Funding
- National Research Foundation of Korea [2020M2D9A3094215]
- Ministry of Science and ICT, Republic of Korea
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Stimulus-responsive self-assembling prodrug-based nanomedicine has emerged as a novel paradigm in controlled drug delivery, showing potential in cancer treatment by releasing multiple active substances and exerting cooperative anticancer effects.
Stimulus-responsive self-assembling prodrug-based nanomedicine has emerged as a novel paradigm in controlled drug delivery. All-trans retinoic acid (RA), one of vitamin A metabolites, induces apoptotic cancer cell death, but its clinical applications are limited by weak anticancer efficacy. To fully maximize the therapeutic potential of RA, we exploited the unique chemistry of arylboronic acid which undergoes hydrogen peroxide (H2O2)-triggered degradation to release quinone methide (QM) that alkylates glutathione (GSH) to disrupt redox homeostasis and is also converted into hydroxybenzyl alcohol (HBA) to suppress the expression of vascular endothelial growth factor (VEGF). Here, we report that boronated retinoic acid prodrug (RABA) can be formulated into selfdeliverable nanoassemblies which release both RA and QM in a H2O2-triggered self-immolative manner to exert cooperative anticancer activities. RABA nanoassemblies exert anticancer effects by inducing reactive oxygen species (ROS)-mediated apoptosis, eliciting immunogenic cell death (ICD) and suppressing angiogenic VEGF expression. The excellent anticancer efficacy of RABA nanoassemblies can be explained by benefits of selfassembling prodrug-based drug self-delivery and cooperative anticancer actions. The design strategy of RABA would provide a new insight into the rational design of self-deliverable and self-immolative boronated prodrug nanoassemblies for targeted cancer therapy.
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