Nanoparticles (NPs) camouflaged in cell membranes represent novel biomimetic platforms that can mimic some of the membrane functions of the cells from which these membranes are derived, in biological systems. Studies using cell membrane coated NPs cover a large repertoire of membranes derived from cells such as red blood cells, immune cells, macrophages, and cancer cells. Cancer cell membrane coated nanoparticles (CCMCNPs) typically consist of a NP core with a cancer cell plasma membrane coat that can carry tumor-specific receptors and antigens for cancer targeting. The NP core can serve as a vehicle to carry imaging and therapeutic moieties. As a result, these CCMCNPs are being investigated for multiple purposes including cancer theranostics. Here we have discussed the key steps and major issues in the synthesis and characterization of CCMCNPs. We have highlighted the homologous binding mechanisms of CCMCNPs that are being investigated for cancer targeting, and have presented our data that identify BT474 CCMCNPs as binding to multiple cancer cell lines. Current preclinical applications of CCMCNPs for cancer theranostics and their advantages and limitations are discussed.

Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies. A compendium of markers such as CD44^high/CD24^low and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed a CD44-targeted monoclonal antibody photosensitizer conjugate for combined fluorescent detection and photoimmunotherapy (PIT) of CD44 expressing cells in TNBC. The CD44-targeted conjugate demonstrated acute cell killing of breast cancer cells with high CD44 expression. This cell death process was dependent upon CD44-specific cell membrane binding combined with near-infrared irradiation. The conjugate selectively accumulated in CD44-positive tumors and caused dramatic tumor shrinkage and efficient elimination of CD44-positive cell populations following irradiation. This novel phototheranostic strategy provides a promising opportunity for the destruction of CD44-positive populations that include cancer stem-like cells, in locally advanced primary and metastatic TNBC.