Abstract
Multiple myeloma (MM) is the second most prevalent hematologic malignancy worldwide. Proteasome inhibitors (PIs) are currently first-line clinical therapies, yet drug resistance has become a major challenge in clinical diagnosis and treatment. The invasiveness of bone marrow biopsies and the low sensitivity of serum monoclonal protein assays impede the early and precise assessment of proteasome inhibitors (PIs) resistance. Circulating MM cells (CMMCs) enable minimally invasive, dynamic monitoring of PI efficacy but are limited by insufficient sensitivity and specificity of current detection methods. In this study, an engineered and robust immunomagnetic nanoprobe (Fe3O4@NH2- ${\mathrm{MIL}}_{\text {88 {B}}}$ @CD138/CD38) was fabricated, by effectively loading magnetic Fe3O4 nanoparticles onto metal-organic framework nanorods (NH2- ${\mathrm{MIL}}_{\text {88 {B}}}\text {)}$ functionalized with dual CD138 and CD38 antibodies. This nanoprobe created an efficient bio-interface to achieve high-efficiency CMMC capture within the range of $8\sim 250$ cells/ $300~\mu $ L. Using 1.0 mL peripheral blood from each patient, we captured CMMCs with the Fe3O4@NH2- ${\mathrm{MIL}}_{\text {88 {B}}}$ @CD138/CD38 nanoprobe and systematically evaluated the correlations between CMMC counts and key clinicopathologic parameters and clinical therapeutic response to PIs in MM patients. CMMC counts were associated with MM clinical stages. Moreover, dynamic changes in CMMC counts measured by this nanoprobe can sensitively reflect responses to PIs therapy. Specifically, CMMC counts were elevated in nearly all patients with progressive disease and decreased in patients with a favorable treatment response. This work provides a potential index for real-time assessing MM disease progression and PIs treatment outcomes.