Abstract

B-cell non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy, capable of invading the brain, meninges, and nerve roots of the brain and spine, leading to high lethality. Herein, we designed and developed novel nanostructures for the first time by biofunctionalizing chitosan with two specific antibodies (i.e., anti-CD20, anti-CD19, and bispecific biopolymer-antibody) against NHL, conjugated with fluorescent nanoprobes. These bioengineered immunoconjugates formed water-dispersed hybrid colloidal nanostructures consisting of a photoluminescent ZnS-based quantum dots core and an antibody-modified chitosan macromolecular shell. The aim was to apply them simultaneously for the diagnosis, bioimaging, and immunotherapy of NHL cancers. The chitosan backbone was covalently functionalized with anti-CD20, anti-CD19, and both antibodies, resulting in biocompatible immunoconjugates through an eco-friendly aqueous process. Importantly, these biopolymer-antibody nanoimmunoconjugates exhibited bioaffinity for both antigenic membrane receptors, CD19 and CD20, which are overexpressed by NHL cancer cells. They served as fluorescent nanoprobes for bioimaging and specifically killing NHL cells, while remarkably preserving nonmalignant cells. Furthermore, biopsies from tumor tissues of a patient with NHL confirmed the effective anticancer potential for clinical applications in fluorescent ex vivo immunohistochemistry diagnosis of NHL cancers. It can be envisioned that these dual-antibody-modified biopolymer nanoarchitectures offer a new realm to be exploited in immunotheranostic applications for fighting cancer.