Self-deliverable and self-immolative prodrug nanoassemblies as tumor targeted nanomedicine with triple cooperative anticancer actions.

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 self-deliverable 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 self-assembling 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.

Diffuse Large B-Cell Lymphoma Arising within Ileal Neobladder: An Expanding Spectrum of Diffuse Large B-Cell Lymphoma Associated with Chronic Inflammation.

Diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI), specifically arising in ileal neobladder, is a rare neoplasm. We present an unusual case of Epstein- Barr virus (EBV)-positive DLBCL-CI arising within neobladder with detailed clinical, histological, and immunophenotypical features in an immunocompetent patient. An 88-year-old male was admitted for gross hematuria. He had undergone radical cystectomy and ileal neobladder 17 years ago for invasive bladder cancer. Computed tomography showed enhancing lesions on dome and posterior wall of neobladder with mucosal thickening and multiple enlarged retroperitoneal lymphadenopathies. Transurethralresection of neobladder lesion revealed the diffuse infiltration of large lymphoid cells which were positive for CD20, CD30, and multiple myeloma oncogen-1 with EBV-encoded small RNAs co-localizing, and diagnosis of EBV-positive DLBCL-CI was made. After multi-agent chemotherapy, the lesion disappeared. We suggest that clinicians should consider the possibility of DLBCL-CI in patients presented with hematuria during follow-up after bladder reconstruction.