Patient-Specific Nanoparticle Targeting in Human Leukemia Blood

Y Ju; S Li; AEQ Tan; EH Pilkington; PT Brannon; M Plebanski; J Cui; F Caruso; KJ Thurecht; C Tam; SJ Kent

Journal article

Patient-Specific Nanoparticle Targeting in Human Leukemia Blood

Y Ju, S Li, AEQ Tan, EH Pilkington, PT Brannon, M Plebanski, J Cui, F Caruso, KJ Thurecht, C Tam, SJ Kent

ACS Nano | AMER CHEMICAL SOC | Published : 2024

DOI: 10.1021/acsnano.4c09919

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Abstract

Antibody-directed targeting of chemotherapeutic nanoparticles to primary human cancers holds promise for improving efficacy and reducing off-target toxicity. However, clinical responses to targeted nanomedicines are highly variable. Herein, we prepared and examined a matrix of 9 particles (organic and inorganic particles of three surface chemistries with and without antibody functionalization) and developed an ex vivo model to study the person-specific targeting of nanoparticles in whole blood of 15 patients with chronic lymphocytic leukemia (CLL). Generally, anti-CD20-functionalized poly(ethylene glycol) (PEG) nanoparticles efficiently targeted CLL cells, leading to low off-target phagocyto..

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University of Melbourne Researchers

Yi David Ju Author

Paul Brannon Author

Frank Caruso Author

Constantine Tam Author

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Grants

Awarded by RMIT University

Funding Acknowledgements

We thank the participation of volunteers for their generous involvement and provision of blood samples. We thank D. Westerman, D. Ritchie, M. Dickinson, and A. Whitechurch (Peter MacCallum Cancer Centre) and R. Koldej (Royal Melbourne Hospital) for assistance with subject recruitment. We thank C.B. Howard and P. Huda (University of Queensland) for providing the BsAbs and T.H. Amarasena (University of Melbourne) for technical assistance. We acknowledge the Materials Characterisation and Fabrication Platform (MCFP) at The University of Melbourne for the use of the confocal microscopy and SIM. Transmission electron microscopy analyses were conducted using the facilities at the Biosciences Microscopy Unit, School of Bioscience, The University of Melbourne. We acknowledge the Ramaciotti Centre for Cryo-Electron Microscopy for instrument use. This study was supported by an Australian Research Council (ARC) Discovery Project (DP210103114 to F.C., S.J.K., Y.J.), an ARC Discovery Early Career Researcher Award (DE230101542, Y.J.), a Maxwell Eagle Endowment Award for Cancer Research (Y.J. and S.J.K.), an RMIT Vice-Chancellor's Postdoctoral Fellowship (Y.J.), an NHMRC program grant (GNT1149990, S.J.K. and F.C.), and NHMRC Investigator grants (S.J.K.; K.T.; and GNT2016732 to F.C.). Figures a, a, and Table of Contents graphic were created with BioRender.com.