Multiple Myeloma-Derived Cellular Lipids Enhance Targeting and Efficacy of Nanoliposome Formulations In Vitro

Multiple myeloma (MM) is a blood cancer characterized by the accumulation of abnormal plasma cells within the bone marrow (BM). The neoplastic expansion progressively disrupts normal blood cell production by outcompeting healthy hematopoietic cells. The disease is characterized by terminally differentiated B cells that secrete antibodies as part of an adaptive immune response. A serious threat confronting small drug molecule therapy for MM is the lack of selective drug targeting, ultimately resulting in insufficient accumulation of drugs to target cells, and harmful off-target drug effects. We now report on the use of cellular lipid extracts (LEs) originating from two different human multiple myeloma (target) cell lines, RPMI 8226 and NCI H929, to develop RPMI 8226 LE- and NCI H929 LE-modified nanoliposomes, respectively. Other ingredients included phospholipid DOPC (dioleoyl-phosphatidylcholine) and/or Chol (cholesterol). Additional cell lines included non-target (Y79-retinoblastoma, U937-lymphoma, K562-GFP-chronic myeloid leukemia) and (off-target) normal healthy PBMCs-peripheral blood mononuclear cells. The LE-modified nanoliposomes stably incorporated various cytotoxic agents, demonstrating novel formulation characteristics and cell-interaction profiles. RPMI 8226 LE enhanced nanoliposome targeting to source-originating RPMI 8226 cells, with diminished uptake by Y79 and PBMCs. The inclusion of Chol reduced targeting to RPMI 8226 cells. The RPMI 8226 LE enhanced nano-formulation effects against RPMI 8226 cells, but not against the Y79 control. Consistent with these findings, RPMI 8226 LE-modified nano-formulations enhanced extracellular lactate dehydrogenase release against RPMI 8226 cells, but not against the Y79 control. NCI H929 LE material also enhanced targeting and nano-formulation effects against source and non-originating source tumor cells from the BM. Designing nanoliposomes to mimic tumor cell membranes may represent a powerful strategy to treat multiple myeloma. Significance: Cellular membrane lipid extracts derived from multiple myeloma cells enhanced targeting and cytotoxicity while limiting damage to normal healthy cells. The inclusion of LE materials in drug delivery systems may represent a promising strategy to enhance cellular targeting and drug therapy for multiple myeloma.