期刊
NANO LETTERS
卷 18, 期 3, 页码 1908-1915出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.7b05263
关键词
tumor microenvironment; macrophage-membrane coating; cascade-responsiveness; biomimetic delivery system; breast-cancer targeting
类别
资金
- National Science Fund for Distinguished Young Scholars [81425023]
- National Natural Science Foundation of China [81373355]
- Fudan-SIMM Joint Research Fund [FU-SIMM 20174009]
- NSF [DMR-1309525]
- NIH [R01 1R01CA207584, R21 CA198684]
- Beckman Institute Graduate Fellowship at the University of Illinois at Urbana-Champaign
Various delivery vectors have been integrated within biologically derived membrane systems to extend their residential time and reduce their reticuloendothelial system (RES) clearance during systemic circulation. However, rational design is still needed to further improve the in situ penetration efficiency of chemo-drug-loaded membrane delivery-system formulations and their release profiles at the tumor site. Here, a macrophage membrane-coated nanoparticle is developed for tumor-targeted chemotherapy delivery with a controlled release profile in response to tumor microenvironment stimuli. Upon fulfilling its mission of tumor homing and RES evasion, the macrophage-membrane coating can be shed via morphological changes driven by extracellular microenvironment stimuli. The nanoparticles discharged from the outer membrane coating show penetration efficiency enhanced by their size advantage and surface modifications. After internalization by the tumor cells, the loaded drug is quickly released from the nanoparticles in response to the endosome pH. The designed macrophage-membrane-coated nanoparticle (cskc-PPiP/PTX@Ma) exhibits an enhanced therapeutic effect inherited from both membrane-derived tumor homing and step-by-step controlled drug release. Thus, the combination of a biomimetic cell membrane and a cascade-responsive polymeric nanoparticle embodies an effective drug delivery system tailored to the tumor microenvironment.
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