title: Investigation of the stability and cellular uptake of self-associated monoclonal antibody (MAb) nanoparticles by non-small lung cancer cells.
abstract: The inability to deliver MAbs to intracellular targets still remains a limitation to their application in cancer therapy and diagnosis. Selective targeting of MAbs to oncoproteins in cancer cells while avoiding their accumulation in normal cells may reduce some of the well-documented adverse effects accompanying antibody therapy. One of the remarkable characteristics of malignant cells is the alteration in the biological properties of the cellular plasma membrane. Taking advantage of this alteration, we hope to selectively deliver self-associated MAb nanoparticles to cancer cells while reducing their accumulation in normal cells. We hypothesized that self-associated MAb nanoparticles can be preferentially taken up by non-small lung cancer cells in comparison to normal cells due to the absence or dysfunction of tight junctions (TJ) in confluent cancer cells and increased permeability of the cancer cell membrane. Self-associated bevacizumab nanoparticles were prepared and characterized for particle size and biochemical stability. Fluorescence microscopy, TEM, and flow cytometry revealed that these bevacizumab nanoparticles were internalized by A549 cells three times more than MRC-5 cells. Macropinocytosis and energy-dependent pathways were elucidated to be involved in their uptake by A549 cells. Further, uptake was by nonspecific interaction with cell membrane. Results obtained from this study suggest that self-associated MAb nanoparticles can be selectively delivered to cancer cells.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, United States.
authors.forename: Asha R
authors.initials: AR
authors.lastname: Srinivasan
authors.forename: Ashakumary
authors.initials: A
authors.lastname: Lakshmikuttyamma
authors.forename: Sunday A
authors.initials: SA
authors.lastname: Shoyele
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D004705:Endocytosis / Q000502:physiology; D006801:Humans; D053758:Nanoparticles / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal