GOLD NANOPARTICLES CONJUGATED WITH RITUXIMAB FOR
THE TREATMENT OF CHRONIC LYMPHOCYTIC LEUKAEMIA
SANDA BOCA1,2 #, CIPRIAN LUCAN3 #, IOANA FRINC4 #, BOBE PETRUSHEV5, TIMEA SIMON1,2, CRISTIAN BERCE6, GRIGORE-ARISTIDE GAFENCU7, DELIA DIMA4, ALINA TANASE8, SONIA SELICEAN7, VALENTINA PILECZKI7,9, LAURA POP7, VLAD MOISOIU7, ANCA
BUZOIANU10, ADRIAN FLOREA11, ALEXANDRU IRIMIE12,13, SIMION ASTILEAN1,2, ANCA BOJAN4,14, IOANA BERINDAN-NEAGOE7,10, CIPRIAN TOMULEASA4,7*
1Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute in Bio-Nano-Sciences, “Babes-
Bolyai” University Cluj-Napoca, Romania
2Faculty of Physics, “Babes-Bolyai” University, Cluj-Napoca, Romania
3Department of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
4Department of Haematology, “Ion Chiricuta” Oncology Institute, Cluj-Napoca, Romania
5Department of Pathology, Emergency County Hospital, Cluj-Napoca, Romania
6Animal Facility, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
7Research Center for Functional Genomics and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy,
Cluj-Napoca, Romania
8Department of Stem Cell Transplantation, Fundeni Clinical Institute, Bucharest, Romania
9Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
10Department of Pharmacology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
11Department of Cell and Molecular Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
12 Department of Surgical and Gynaecological Oncology, “Ion Chiricuta” Oncology Institute, Cluj-Napoca, Romania
13Department of Surgery, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
14Department of Haematology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
*corresponding author: ciprian.tomuleasa@umfcluj.ro
#These authors contributed equally to the current paper, being all three considered co-first authors.
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Abstract:
Despite the considerable progress in the chronic lymphocytic leukaemia (CLL) therapy, relapse or progression to a Richter
syndrome still appears. Thus, a more targeted therapeutic option is required. This can be achieved by increasing the
concentration of the cytostatic drug in the tumour while reducing its systemic toxicity. In the continuous effort toward the
development of more efficient therapeutics, in the current study we report rituximab conjugated gold nanoparticles for CLL
treatment. The formation of rituximab-nanoconjugates was proved by physico-chemical characterization (UV-Vis spectroscopy,
zeta potential and dynamic light scattering) and their intracellular internalization was assessed by dark field and transmission
electron microscopy. The therapeutic effect of the newly-designed drugs was investigated by cell counting and MTT assays.
Results showed that the effect of our drug-nanocarrier is superior compared to that of the drug alone, data confirmed by stateof-
the-art analyses of internalization, cell biology (flow cytometry, apoptosis and autophagy assay), genomics (RT-PCR for
MS4A1) and proteomics (confocal microscopy and western blotting for CD20). The present work demonstrates that
rituximab nanoconjugates can get an efficient trans-membrane delivery inside CLL cells, being validated as real-potential
therapeutics with increased efficacy compared to the drug alone.






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