Reassembly of 89Zr-Labeled Cancer Cell Membranes into Multicompartment Membrane-Derived Liposomes for PET-Trackable Tumor-Targeted Theranostics

Abstract

Nanoengineering of cell membranes holds great potential to revolutionize tumor-targeted theranostics, owing to their innate biocompatibility and ability to escape from the immune and reticuloendothelial systems. However, tailoring and integrating cell membranes with drug and imaging agents into one versatile nanoparticle are still challenging. Here, multicompartment membrane-derived liposomes (MCLs) are developed by reassembling cancer cell membranes with Tween-80, and are used to conjugate ⁸⁹Zr via deferoxamine chelator and load tetrakis(4-carboxyphenyl) porphyrin for in vivo noninvasive quantitative tracing by positron emission tomography imaging and photodynamic therapy (PDT), respectively. Radiolabeled constructs, ⁸⁹Zr-Df-MCLs, demonstrate excellent radiochemical stability in vivo, target 4T1 tumors by the enhanced permeability and retention effect, and are retained long-term for efficient and effective PDT while clearing gradually from the reticuloendothelial system via hepatobiliary excretion. Toxicity evaluation confirms that the MCLs do not impose acute or chronic toxicity in intravenously injected mice. Additionally, ⁸⁹Zr-labeled MCLs can execute rapid and highly sensitive lymph node mapping, even for deep-seated sentinel lymph nodes. The as-developed cell membrane reassembling route to MCLs could be extended to other cell types, providing a versatile platform for disease theranostics by facilely and efficiently integrating various multifunctional agents.

Systematic noninvasive tracking and quantitative investigation of ⁸⁹Zr-labeled multicompartment membrane-derived liposomes (⁸⁹Zr-Df-MCLs) is performed to demonstrate rapid clearance of ⁸⁹Zr-Df-MCLs, which is estimated to be over 63% injected dose (ID) at 72 h post-injection through the hepatobiliary route. ⁸⁹Zr-Df-MCLs are developed as contrast agents for positron emission tomography for in vivo imaging of tumors and mapping of lymph nodes, as well as for fluorescence imaging and photodynamic therapy after loading with a porphyrin cargo.

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