Bioinspired lipoproteins-mediated photothermia remodels tumor stroma to improve cancer cell accessibility of second nanoparticles

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 bLPmediated 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.

Engineering precision nanoparticles for drug delivery

“…Other studies use magnetic NPs 63 or AuNPs 64,65 , which are simple to use, in biomarker detection assays, thereby saving time and money if compared with existing methods that require substantial sample processing. In addition to diagnostic screening, some therapeutic applications of NPs aim to remodel the tumour microenvironment to promote particle accumulation and penetration, and thus increase drug efficacy, and/or to sensitize tumours to a particular therapy [66][67][68] . For example, tumour-associated endothelial cells can be manipulated by a NP-delivered microRNA, which alters the tumour vasculature and thereby sensitizes the tumour to traditional cancer therapies 67 .…”

<p>Her2-Targeted Multifunctional Nano-Theranostic Platform Mediates Tumor Microenvironment Remodeling and Immune Activation for Breast Cancer Treatment</p>

“…27 Therefore, the DOX-loaded nanoparticles we developed can enhance the ICD effect at a tumor site specifically. Moreover, tumor microenvironment remodeling mediated by photothermal therapy increases the accessibility of nanoparticles to tumor cells, 19 which undoubtedly amplifies the antitumor and ICD effect brought by DOX. However, we only developed a BT474 breast cancer cell nude mice model, and lacked a BT474/Adr breast cancer model.…”

Metastatic status of sentinel lymph nodes in breast cancer determined with photoacoustic microscopy via dual-targeting nanoparticles

“…Breast cancer cells are well known to overexpress CD44 proteins. Recently, Tao et al reported that SR-B1 is also expressed on breast cancer cells 26 . Previously, we developed an HPPS nanoparticle with strong SR-B1 targeting ability 24 .…”

“…Previously, we developed a high-density lipoprotein (HDL)-mimicking peptide–phospholipid scaffold (HPPS) with hydrodynamic diameters of 10–30 nm 24 that can migrate to LNs by size-dependent passive transport 21 , 25 . Moreover, HPPS nanoparticles can target scavenger receptor class B type 1 (SR-B1), which is expressed on breast cancer cells 26 . Herein, we developed a novel dual-targeting nanoparticle by inserting the negatively charged HA-1,2-dimyristoyl phosphatidylethanolamine (DMPE) into a single-layer phospholipid of HPPS, denoted HA-HPPS.…”