Abstract
Retrieval of circulating tumor cells (CTC) has proven valuable for assessing a patient's cancer burden, evaluating response to therapy, and analyzing which drug might treat a cancer best. Although most isolation methods retrieve CTCs based on size, shape, or capture by tumor-specific antibodies, we explore here the use of small molecule tumor-specific ligands linked to magnetic beads for CTC capture. We have designed folic acid-biotin conjugates with different linkers for the capture of folate receptor (FR) + tumor cells spiked into whole blood, and application of the same technology to isolate FR + CTCs from the peripheral blood of both tumor-bearing mice and non-small cell lung patients. We demonstrate that folic acid linked via a rigid linker to a flexible PEG spacer that is in turn tethered to a magnetic bead enables optimal CTC retrieval, reaching nearly 100% capture when 100 cancer cells are spiked into 1 mL of aqueous buffer and ~ 90% capture when the same quantity of cells is diluted into whole blood. In a live animal model, the same methodology is shown to efficiently retrieve CTCs from tumor-bearing mice, yielding cancer cell counts that are proportional to total tumor burden. More importantly, the same method is shown to collect ~ 29 CTCs/8 mL peripheral blood from patients with non-small cell lung cancer. Since the ligand-presentation strategy optimized here should also prove useful in targeting other nanoparticles to other cells, the methods described below should have general applicability in the design of nanoparticles for cell-specific targeting.
Original language | English (US) |
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Article number | 8555 |
Pages (from-to) | 8555 |
Journal | Scientific Reports |
Volume | 12 |
Issue number | 1 |
DOIs | |
State | Published - May 20 2022 |
Keywords
- Animals
- Carcinoma, Non-Small-Cell Lung
- Cell Count
- Cell Line, Tumor
- Cell Separation/methods
- Folic Acid
- Humans
- Ligands
- Lung Neoplasms
- Mice
- Molecular Weight
- Neoplastic Cells, Circulating/pathology
ASJC Scopus subject areas
- General