Main Article Content
Abstract
Background: Synthetic nanocarrier drug delivery systems face a fundamental biological challenge: the immune system recognizes them as foreign materials, triggering rapid opsonization, complement activation, and phagocytic clearance by the mononuclear phagocyte system that removes the majority of intravenously injected nanoparticles from circulation within minutes to hours, limiting their accumulation at intended therapeutic targets. Biomimetic nanocarriers — nanoparticles coated with natural cell membranes or functionalized with biological molecules derived from cells — address this challenge by disguising synthetic nanoparticle cores within biological cloaks that inherit the immune-evasive surface properties, cell-type-specific homing molecules, and functional proteins of the source cells, enabling nanocarriers to circulate in blood, penetrate biological barriers, and target specific tissues with a degree of biological specificity inaccessible to conventional PEGylated synthetic nanoparticles.
Objective: This review comprehensively examines the biological rationale, preparation technologies, characterization methods, mechanisms of immune evasion and cellular targeting, and therapeutic applications of biomimetic cell membrane-coated nanocarriers derived from red blood cells, white blood cells, platelets, cancer cells, stem cells, and hybrid membranes, with emphasis on research advances through 2024.
Results and Discussion: Cell membrane-coated nanocarriers from diverse source cells demonstrate superior circulation half-lives (two- to fivefold longer than equivalent PEGylated nanoparticles), organ- and cell-type-specific biodistribution patterns determined by the source cell's natural homing behavior, and preservation of functional surface proteins including CD47 (don't-eat-me signaling), integrin complexes (cell adhesion), and receptor ligands (homotypic targeting) that collectively provide biological targeting specificity unobtainable by synthetic surface functionalization. Hybrid membrane systems combining membrane components from two or more cell types create designer biomimetic surfaces with combined biological functions exceeding what any single cell membrane can provide.
Conclusion: Biomimetic cell membrane-coated nanocarriers represent one of the most biologically sophisticated drug delivery platforms to emerge in the past decade, offering immune evasion, biological targeting, and functional protein retention that collectively address the most fundamental limitations of synthetic nanocarrier systems. Scale-up of cell membrane extraction and coating processes, quality control of biological membrane preparations, and clarification of the regulatory pathway for this novel hybrid bio-synthetic product class are the principal translation barriers requiring resolution.