Selective Targeting of Lymphoma Cells by Monoclonal Antibody Grafted onto Zwitterionic-Functionalized Nanoparticles

Author(s)

Affonso de Oliveira, Jessica Fernanda ^{[1, 2]} ; da Silva, Raquel Frenedoso ^[2] ; Sousa Ribeiro, Iris Renata ^{[1, 2]} ; Saito, Angela ^[3] ; Melo-Hanchuk, Talita Diniz ^[4] ; Dias, Marilia Meira ^[3] ; Kobarg, Jorg ^{[4, 5]} ; Cardoso, Mateus Borba ^{[1, 2]}

Affiliation

^[1] Univ Estadual Campinas UNICAMP, IQ, Caixa Postal 6154, BR-13083970 Campinas, SP - Brazil

^[2] CNPEM, Lab Nacl Nanotecnol LNNano, Caixa Postal 6192, BR-13083970 Campinas, SP - Brazil

^[3] Lab Nacl Biociencias LNBio, Caixa Postal 6192, BR-13083970 Campinas, SP - Brazil

^[4] Univ Estadual Campinas UNICAMP, IB, Programa Posgrad Biol Func & Mol, Dept Bioquim & Biol Tecidual, Caixa Postal 6154, BR-13083970 Campinas, SP - Brazil

^[5] Univ Estadual Campinas UNICAMP, Fac Ciencias Farmaceut, Caixa Postal 6154, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION; v. 37, n. 3 FEB 2020.
• Web of Science Citations: 1

Abstract

Nanomedicine is considered a promising alternative to improve cancer diagnosis and treatment. Particularly, the use of nanoparticles (NPs) has enabled the encapsulation of highly toxic anticancer drugs, facilitated ultimate targeting, and allowed tailoring of drug delivery. However, when in biological fluids, these NPs are coated by proteins which hide the targeting moieties and suppress the engineered biological outcome. Herein, how the Ki-1 monoclonal antibody (mAb) can preserve its targetability through grafting on the surface of zwitterionic-functionalized nanoparticles, is unveiled. Zwitterions, known for their stealth ability, are used to minimize unspecific NPs protein adsorption and consequently maintain mAb functionality. In this work, Ki-1 mAb is used as it recognizes TNFRSF8 (CD30(+)) transmembrane protein overexpressed on CD30(+) lymphoma cells such as L540 cells. While nonfunctionalized NPs show negligible toxic effects toward L540 cells, the Ki-1-functionalized structure demonstrates cytotoxicity, since they undergo cellular uptake, suggesting a receptor-mediated internalization. This dual-functionalization strategy provides a promising multifunctional nanoplatform toward future personalized medicine applications, minimizing unspecific protein adsorption on NPs and ensuring selective cancer cell targeting. (AU)

• FAPESP's process: 14/22322-2 - Functionalization of silica nanoparticles: increasing biological interaction
• Grantee: Mateus Borba Cardoso
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/25406-5 - Organizing matter: colloids formed by association of surfactants, polymers and nanoparticles
• Grantee: Watson Loh
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/22429-9 - Synthesis of mesoporous silica nanoparticles functionalized with monoclonal antibodies: an alternative to Hodgkin (HL) and anaplastic large cell CD30+ (ALCL - CD30+) lymphomas treatment
• Grantee: Jessica Fernanda Affonso de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/21318-0 - Targeting of functionalized nanoparticles in microfluidics systems containing multiple organoids
• Grantee: Iris Renata Sousa Ribeiro
• Support Opportunities: Scholarships in Brazil - Doctorate