Optimal Physicochemical Properties of Antibody–Nanoparticle Conjugates for Improved Tumor Targeting

Abstract

Tumor‐targeted antibody (mAb)/fragment‐conjugated nanoparticles (NPs) represent an innovative strategy for improving the local delivery of small molecules. However, the physicochemical properties of full mAb–NPs and fragment–NPs—that is, NP material, size, charge, as well as the targeting antibody moiety, and the linker conjugation strategies—remain to be optimized to achieve an efficient tumor targeting. A meta‐analysis of 161 peer‐reviewed studies is presented, which describes the use of tumor‐targeted mAb–NPs and fragment−NPs from 2009 to 2021. The use of these targeted NPs is confirmed to result in significantly greater tumor uptake of NPs than that of naked NPs (7.9 ± 1.9% ID g−1 versus 3.2 ± 0.6% ID g−1, respectively). The study further demonstrates that for lipidic NPs, fragment–NPs provide a significantly higher tumor uptake than full mAb–NPs. In parallel, for both polymeric and organic/inorganic NPs, full mAb–NPs yield a significant higher tumor uptake than fragment–NPs. In addition, for both lipidic and polymeric NPs, the tumor uptake is improved with the smallest sizes of the conjugates. Finally, the pharmacokinetics of the conjugates are demonstrated to be driven by the NPs and not by the antibody moieties, independently of using full mAb–NPs or fragment–NPs, confirming the importance of optimizing the NP design to improve the tumor uptake.

Behavior of Citrate-Capped Ultrasmall Gold Nanoparticles on a Supported Lipid Bilayer Interface at Atomic Resolution

“…The inability of the AuNP to successfully embed completely within the gel-phase bilayer (i.e., interfacial interaction) has potential implications for other hard–soft matter or lipid–NP interactions and other biological–bilayer interactions, as other materials with similar properties may exhibit similar behavior. The ability of the AuNP to localize within the central core of the fluid-phase bilayer has potential applications in targeting specific membrane embedded protein anchorage motifs (i.e., nonpolar/hydrophobic regions of proteins). , Specificity of these domains and functionality can be further enhanced via AuNP–protein/peptide conjugation, − while cell penetration can be enhanced via alteration of ligand coating and conjugation to cell-penetrating peptides . The ability of the AuNP to potentially translocate across the gel-phase bilayer upper leaflet surface allows it to potentially illicit effects and/or delivery compounds to the cell without direct interference with intracellular organelles or other cellular constituents.…”

Antibody‐Incorporated Nanomedicines for Cancer Therapy

“…[ 454 ] Additionally, Mittelheisser et al further confirmed that the tumor‐targeting antibody‐nanoparticle conjugates could exhibit significantly increased tumor uptake compared with non‐targetable nanoparticles in a recent meta‐analysis study. [ 655 ] Also, as mentioned before, various studies have demonstrated the enhanced tumor accumulation of antibody‐conjugated nanoparticles in comparison with that of non‐targetable nanoparticles in both in vitro cell models and in vivo mouse models. Besides, compared with non‐targetable nanoparticles, the antibody‐modified nanoparticles can realize enhanced anticancer efficacy since the antibody functionalization can promote the cellular uptake of the nanoparticles via the receptor‐mediated endocytic pathway.…”

Dye-sensitized lanthanide containing nanoparticles for luminescence based applications

“…The acryl function enabled to covalently bind the complexes to the host matrix thanks to its involvement in the copolymerization process and to avoid a possible leakage from the particles over time. At the same period, [Eu (48) 3 ] doped PSt NPs were also commercialized and have been extensively used by Härmä and colleagues over the years for improving bioanalytical methods (immunoassays, [136][137][138][139] cell imaging, 140 protein quantification 141 and protein aggregation 142,143 ). The 107 nm NPs in particular were found to contain 31000 chelates and to exhibit an Eu-based luminescence emission lifetime of circa 720 µs.…”

“…multiple analysis with a same sample 44 or multimodal analytical devices. 45 On the other hand, the larger size and composition of NPs compared to Ln complexes can bring significant issues regarding toxicity, 46,47 possible unwanted size dependent pharmacokinetic and bio-distribution properties, 48 or simple stability troubles such as leaching in biological media. 49,50…”

“…multiple analysis with a same sample 44 or multimodal analytical devices. 45 On the other hand, the larger size and composition of NPs compared to Ln complexes can bring significant issues regarding toxicity, 46,47 possible unwanted size dependent pharmacokinetic and biodistribution properties, 48 or simple stability troubles such as leaching in biological media. 49,50 With regards to these different considerations on Ln luminescence, the next chapters aim at reviewing the main works reporting on the three principal strategies developed so far for improving Ln luminescence with the help of nanoscopic scaffolds.…”