Abstract
Cancer is a global health problem in need of transformative treatment solutions for improved patient outcomes. Many conventional treatments prove ineffective and produce undesirable side effects because they are incapable of targeting only cancer cells within tumors and metastases post administration. There is a desperate need for targeted therapies that can maximize treatment success and minimize toxicity. Nanoparticles (NPs) with tunable physicochemical properties have potential to meet the need for high precision cancer therapies. At the forefront of nanomedicine is biomimetic nanotechnology, which hides NPs from the immune system and provides superior targeting capabilities by cloaking NPs in cell-derived membranes. Cancer cell membranes expressing “markers of self” and “self-recognition molecules” can be removed from cancer cells and wrapped around a variety of NPs, providing homotypic targeting and circumventing the challenge of synthetically replicating natural cell surfaces. Compared to unwrapped NPs, cancer cell membrane-wrapped NPs (CCNPs) provide reduced accumulation in healthy tissues and higher accumulation in tumors and metastases. The unique biointerfacing capabilities of CCNPs enable their use as targeted nanovehicles for enhanced drug delivery, localized phototherapy, intensified imaging, or more potent immunotherapy. This review summarizes the state-of-the-art in CCNP technology and provides insight to the path forward for clinical implementation.
Highlights
Introduction to Cancer and NanomedicineCancer is a devastating global public health problem in desperate need of transformative solutions.It is the second leading cause of death in the United States and predicted to take 1700 lives per day in 2019 [1]
The cancer cell membrane-wrapped NPs (CCNPs) is composed of a poly(lactic-co-glycolic acid) (PLGA) core surrounded by a membrane derived from a 4T1 mouse breast cancer cell
Fang et al showed by Western blotting that CCNPs prepared by physically extruding PLGA NPs with B16-F10 mouse melanoma membranes collected by hypotonic lysis were positive for the membrane markers pan-cadherin, Na+ /K+ -ATPase, and gp100, but lacked the intracellular markers histone H3, cytochrome c oxidase, and glyceraldehyde 3-phosphate dehydrogenase [45]
Summary
Cancer is a devastating global public health problem in desperate need of transformative solutions. Ligands that are too densely packed on an NP surface can cause a non-cooperative effect on target receptor binding, increased uptake by immune cells, and nonspecific binding to perivascular cells after extravasation [21,23,24] This limits the NPs’ success due to low circulation time, early clearance from the body, and unwanted immune responses [16,18,19]. Serum proteins and opsonins can quickly coat ligand-targeted NPs in the bloodstream, rendering the targeting agents ineffective and increasing the rate of NP clearance from the body These shortcomings create a need for surface modifications that can better disguise nanovehicles from the immune system, prolong circulation time, and provide enhanced targeting and cell internalization capabilities.
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