Department of Bioengineering, School of Engineering and Applied Sciences , University of Pennsylvania , Philadelphia , Pennsylvania 19104 , United States.
Department of Radiology, Division of Neuroradiology , Hospital of the University of Pennsylvania , Philadelphia , Pennsylvania 19104 , United States.
ACS Nano. 2020 Jan 28;14(1):142-152. doi: 10.1021/acsnano.9b05660. Epub 2019 Dec 23.
Drug delivery to solid tumors is hindered by hydrostatic and physical barriers that limit the penetration of nanocarriers into tumor tissue. When exploiting the enhanced permeability and retention (EPR) effect for passive targeting of nanocarriers, the increased interstitial fluid pressure and dense extracellular matrix in tumors limits the distribution of the nanocarriers to perivascular regions. Previous strategies have shown that magnetophoresis enhances accumulation and penetration of nanoparticles into solid tumors. However, because magnetic fields fall off rapidly with distance from the magnet, these methods have been limited to use in superficial tumors. To overcome this problem, we have developed a system comprising two oppositely polarized magnets that enables the penetration of magnetic nanocarriers into more deeply seeded tumors. Using this method, we demonstrate a 5-fold increase in the penetration and a 3-fold increase in the accumulation of magnetic nanoparticles within solid tumors compared to EPR.
药物递送至实体瘤受到静水压力和物理屏障的阻碍,限制了纳米载体进入肿瘤组织的穿透能力。在利用增强型通透性和保留(EPR)效应进行纳米载体的被动靶向时,肿瘤中增加的细胞间液压力和致密的细胞外基质限制了纳米载体的分布仅限于血管周围区域。以前的策略表明,磁泳可增强纳米颗粒在实体瘤中的积累和穿透。然而,由于磁场从磁铁迅速衰减,这些方法仅限于用于浅层肿瘤。为了克服这个问题,我们开发了一种由两个极性相反的磁铁组成的系统,使磁性纳米载体能够穿透更深植入的肿瘤。使用这种方法,与 EPR 相比,我们证明了磁性纳米颗粒在实体瘤中的穿透增加了 5 倍,积累增加了 3 倍。
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