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

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.

Antibody‐Incorporated Nanomedicines for Cancer Therapy

“…Considered as a hopeful approach to improve cancer diagnosis and treatment, nanoparticles allow tailored drug delivery with reduced systemic toxicity and enhanced targeting. [ 30 ] Nanoscale drug carriers which can realize targeted delivery of chemotherapeutic agents or therapeutic genes without affecting healthy cells have created new potential for cancer detection and treatment. [ 31 ] Bioconjugation is a strategy referring to the combination of biologically active molecules and nanoparticles through different methods, and it endows nanoparticles with novel and improved features.…”

“…Based on this study, anti‐CD30 mAbs were conjugated onto the nanoparticles with pre‐functionalized amino moieties for targeting the CD30 + lymphoma cells, and the corresponding experimental results validated the feasibility of using this dual functionalization strategy to achieve successful cancer treatment. [ 30 ] Furthermore, a pre‐formed protein corona of albumin or antibodies can avoid the plasma protein adsorption of nanoparticles by developing a protective coating. [ 78 ] For instance, Tonigold et al discussed the feasibility of pre‐adsorbing targeting antibodies on the surface of nanoparticles before the introduction of different concentrations of serum or plasma.…”

Dual-Functionalized Architecture Enables Stable and Tumor Cell-Specific SiO2NPs in Complex Biological Fluids

“…Once in contact with blood, NPs interact with a series of physiological components (e.g., amino acids, salts, and proteins), which can induce poor colloidal stability or changes in these particles' original chemical and biological identity, impairing their therapeutic efficiency [12][13][14][15]. Proteins and other biomolecules can be adsorbed on the surface of NPs (protein corona formation), masking their original functionality and hiding their target ability [16][17][18]. Protein corona can further lead to the formation of aggregates of NPs and the activation of unplanned biological pathways (e.g., the complement system) [16][17][18].…”

“…Proteins and other biomolecules can be adsorbed on the surface of NPs (protein corona formation), masking their original functionality and hiding their target ability [16][17][18]. Protein corona can further lead to the formation of aggregates of NPs and the activation of unplanned biological pathways (e.g., the complement system) [16][17][18]. The factors mentioned above hamper the biodistribution of nanomedicines and their targeting efficiency, therefore devising adverse effects.…”

“…Multiple functionalization strategies to produce colloidally stable NP dispersions with retained targeting capacity have been widely investigated recently [17,18,20,21]. While a panel of molecules (e.g., polyethylene glycol, zwitterionics, glycans, aptamers) can improve the stability of NPs in biological media by preventing the adsorption of proteins [22,23], developing methods that can meet the trade-off between targeting and colloidal stability of NPs in such media has proven to be a major challenge [8,10,11].…”