Abstract
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.
Highlights
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
By analyzing the particle size, morphology, and compositions of these formulations with natural mature high-density lipoproteins (HDL), the nanosystems of D-bLP and M-bLP could be termed as bioinspired lipoproteins
Thereby, D-bLP-mediated TSM remodeling caused notable improvement of second DiI/M-bLP accumulation in tumor, which was superior to the counterpart liposomal formulations
Summary
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. 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. TAM are believed to shape the tumor stroma by producing proteolytic enzymes and matrix-associated proteins, and are pivotal constructors of tumor collagenous matrix through regulation of CAF16 These stroma cells and multiple ECM components form the tumor stromal microenvironments (TSM) barriers[13,14,15]. We here design a bioinspired lipoprotein (bLP) nanosystem that, respectively, loads photothermal agent of DiOC18(7) (DiR) (termed as D-bLP) and anticancer drug of mertansine (termed as M-bLP), aiming at remodeling TSM barriers with D-bLP-mediated photothermia and augmenting the accessibility of second-wave M-bLP to cancer cells in tumor for efficient suppression of tumor relapse and metastasis (Fig. 1)
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