仿生脂蛋白介导的光热疗法重塑肿瘤基质，提高第二纳米颗粒对癌细胞的可达性。
Bioinspired lipoproteins-mediated photothermia remodels tumor stroma to improve cancer cell accessibility of second nanoparticles.
机构信息
State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
School of Pharmacy, Shenyang Pharmaceutical University, Benxi, 117000, Liaoning, China.
出版信息
Nat Commun. 2019 Jul 25;10(1):3322. doi: 10.1038/s41467-019-11235-4.
The tumor stromal microenvironments (TSM) including stromal cells and extracellular matrix (ECM) form an abominable barrier hampering nanoparticles accessibility to cancer cells, significantly compromising their antitumor effects. Herein, we report a bioinspired lipoprotein (bLP) that can induce efficient photothermia to remodel TSM and improve second bLP accessibility to cancer cells for antitumor therapy. The multiple stromal cells and ECM components in TSM are remarkably disrupted by bLP-mediated photothermal effects, which cause a 4.27-fold enhancement of second bLP accumulation in tumor, deep penetration in whole tumor mass and 27.0-fold increase of accessibility to cancer cells. Of note, this bLP-mediated TSM-remodeling to enhance cancer cell accessibility (TECA) strategy produces an eminent suppression of tumor growth and results in a 97.4% inhibition of lung metastasis, which is superior to the counterpart liposomes. The bLP-mediated TECA strategy provides deeper insights into enhancing nanoparticle accessibility to cancer cells for antitumor therapy.
肿瘤基质微环境（TSM）包括基质细胞和细胞外基质（ECM），形成了一个恶劣的屏障，阻碍了纳米颗粒与癌细胞的接触，显著降低了它们的抗肿瘤效果。在此，我们报告了一种仿生脂蛋白（bLP），它可以诱导有效的光热作用来重塑 TSM，并提高第二个 bLP 对癌细胞的可及性，以进行抗肿瘤治疗。TSM 中的多种基质细胞和 ECM 成分被 bLP 介导的光热效应显著破坏，这导致第二个 bLP 在肿瘤中的积累增加了 4.27 倍，在整个肿瘤质量中的深度渗透增加了 27.0 倍，对癌细胞的可及性增加了 27.0 倍。值得注意的是，这种 bLP 介导的 TSM 重塑以增强癌细胞可及性（TECA）策略显著抑制了肿瘤生长，并导致肺转移的抑制率达到 97.4%，优于相应的脂质体。bLP 介导的 TECA 策略为增强纳米颗粒对癌细胞的可及性以进行抗肿瘤治疗提供了更深入的见解。
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