Role of Nanoparticle Valency in the Nondestructive Magnetic-Relaxation-Mediated Detection and Magnetic Isolation of Cells in Complex Media

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Abstract
Nanoparticle-based diagnostics typically involve the conjugation of targeting ligands to the nanoparticle to create a sensitive and specific nanosensor that can bind and detect the presence of a target, such as a bacterium, cancer cell, protein, or DNA sequence. Studies that address the effect of multivalency on the binding and detection pattern of these nanosensors, particularly on magnetic relaxation nanosensors that sense the presence of a target in a dose-dependent manner by changes in the water relaxation times (ΔT2), are scarce. Herein, we study the effect of multivalency on the detection profile of cancer cells and bacteria in complex media, such as blood and milk. In these studies, we conjugated folic acid at two different densities (low-folate and high-folate) on polyacrylic-acid-coated iron oxide nanoparticles and studied the interaction of these magnetic nanosensors with cancer cells expressing the folate receptor. Results showed that the multivalent high-folate magnetic relaxation nanosensor performed better than its low folate counterpart, achieving single cancer cell detection in blood samples within 15 min. Similar results were also observed when a high molecular weight anti-folate antibody (MW 150 kDa) was used instead of the low molecular weight folic acid ligand (MW 441.4 kDa), although better results in terms of sensitivity, dynamic range, and speed of detection were obtained when the folate ligand was used. Studies using bacteria in milk suspensions corroborated the results observed with cancer cells. Taken together, these studies demonstrate that nanoparticle multivalency plays a key role in the interaction of the nanoparticle with the cellular target and modulate the behavior and sensitivity of the assay. Furthermore, as detection with magnetic relaxation nanosensors is a nondestructive technique, magnetic isolation and further characterization of the cancer cells is possible.

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