Institution: | 1. Laboratório Nacional de Nanotecnologia (LNNano), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), CEP 13083-970, Caixa Postal 6192, Campinas, SP, Brazil
Instituto de Química (IQ), Universidade Estadual de Campinas (UNICAMP), CEP 13083-970, Caixa Postal 6154, Campinas, SP, Brazil;2. Laboratório Nacional de Nanotecnologia (LNNano), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), CEP 13083-970, Caixa Postal 6192, Campinas, SP, Brazil;3. Laboratório Nacional de Biociências (LNBio), CEP 13083-970, Caixa Postal 6192, Campinas, SP, Brazil;4. Departamento de Bioquímica e Biologia Tecidual—Programa de Pós-graduação em Biologia Funcional e Molecular, Instituto de Biologia (IB), Universidade Estadual de Campinas (UNICAMP), CEP 13083-970, Caixa Postal 6154, Campinas, SP, Brazil;5. Departamento de Bioquímica e Biologia Tecidual—Programa de Pós-graduação em Biologia Funcional e Molecular, Instituto de Biologia (IB), Universidade Estadual de Campinas (UNICAMP), CEP 13083-970, Caixa Postal 6154, Campinas, SP, Brazil
Faculdade de Ciências Farmacêuticas, Universidade Estadual de Campinas (UNICAMP), CEP 13083-970, Caixa Postal 6154, Campinas, SP, Brazil |
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. |