C–C Chemokine Ligand 2 (CCL2) Recruits Macrophage-Membrane-Camouflaged Hollow Bismuth Selenide Nanoparticles To Facilitate Photothermal Sensitivity and Inhibit Lung Metastasis of Breast Cancer

Abstract

Poor tumor accumulation, rapid clearance from blood circulation, and high risk of invasive and metastasis are the major barriers that encumber the conventional nanodrug-based tumor therapy. In this work, macrophage membrane (M)-camouflaged quercetin (QE)-loaded hollow bismuth selenide nanoparticles (abbreviated as M@BS-QE NPs) are fabricated for combination therapy of breast cancer. The resulting M@BS-QE NPs are comprehensively characterized, possessing prolonged circulation life, as well as accelerated and enhanced tumoritropic accumulation, compared with those of bare BS NPs because of the immune evading capacity, C-C chemokine ligand 2 (CCL2)-mediated recruitment properties, and active targeting ability. The subsequent QE release under near-infrared (NIR) laser irradiation can selectively sensitize cancer cells to photothermal therapy (PTT) by depleting heat shock protein 70 (HSP70, one malignancy-specific-overexpressed thermoresistance-related chaperone) to realize such a cascaded synergistic effect. At the same time, M@BS-QE NPs down-regulated p-Akt and matrix metalloproteinase-9 (MMP-9, which degrades the extracellular matrix to promote invasion and metastasis of tumors) signal axis to suppress breast cancer lung metastasis. Thus, our results provide a biomimetic strategy, using the characteristics of breast cancer and biological properties of macrophages, that hold great promise to enhance the therapeutic efficacy and improve the accuracy of treatment with minimal side effects on both primary and lung metastasis of breast cancer.

The Contribution of the Immune System in Bone Metastasis Pathogenesis

“…Distinct from M1, TAMs secret high levels of cytokines including IL-10 and TGF-β which decreases the activation of CD4 + and CD8 + T cells [94]. Likewise, emerging evidence including clinical data and animal experiments demonstrate that TAMs potentiate tumor metastasis [95,96,97], particularly bone metastasis [98]. Increased numbers of CD206 + M2-like macrophages have been found in prostate cancer with bone metastatic lesions [98,99].…”

Bistratal Au@Bi2S3 nanobones for excellent NIR-triggered/multimodal imaging-guided synergistic therapy for liver cancer

“…The Au@Bi 2 S 3 -PVP NBs clearly showed a drug encapsulation efficiency comparable to those of the listed Bi-based materials. Moreover, in the simulated tumor microenvironment (pH 5.0), Au@Bi 2 S 3 -PVP/DOX exhibited a higher DOX release rate (46% within 10 h) than the reported membrane-camouflaged quercetin-loaded hollow bismuth selenide nanoparticles (M@BS-QE NPs, ~40% within 10 h) [ 55 ]. Although DOX is a clinically effective anticancer drug, adequate doses during cancer therapy unavoidably produce severe side effects.…”

Biointerface engineering nanoplatforms for cancer-targeted drug delivery

“…The engulfed antigens can then be presented to DCs or T cells after phagocytosis, and the step is essential in antigen-specific immune responses. Similar to monocyte, macrophage membranes have been extracted and used in the manufacture of nanoparticle-based drug delivery systems, and have proven to be crucial in cancer therapy owing to their inherent cell membrane proteins [87] , [88] , [89] , [90] . For example, Zhao et al reported the development of macrophage membrane-coated quercetin (QE)-loaded bismuth selenide nanoparticles (M@BS-QE NPs) for the inhibition of breast cancer lung metastasis [90] .…”

“… Cell derivation Tumor cell targeting Chemokine recruitment Targeted region Cell adhesion molecule for active targeting Targeted ligand or attractant Ref. Cancer cell + − Cancer cell EpCAM, galectin-3, N -cadherin EpCAM, galectin-3, N -cadherin [61] , [62] , [63] , [64] , [65] , [66] WBC + + Cancer cell/TME CXCR2, CCL18, α4 integrin, endothelin-B receptor, CSF-1 receptor, EGF, VEGFR, TCR CXCL1/2/3/4/5/7/8, VCAM-1, GM-CSF ET-2, CSF-1, EGFR, VEGF, Melan-A/MART-1, tyrosinase, gp100, MAGEs, so-called cancer/testis antigens, tumor-restricted antigens [75] , [76] , [77] , [78] , [79] , [80] , [81] , [82] , 90] Platelet + − Cancer cell P-selectin CD44 receptor [105 , 106] Mesenchymal stem cell + + Cancer cell CXCR4, EGF, integrins, extracellular matrix molecules SDF-1, EGFR (HER2) [108] , [109] , [110] , [111] Bacteria + − Cancer cell HA, engineered anti-HER2 affibody CD44 receptor, HER2 [119 , 120] Exosome + − Cancer cell Lysosome-associated membrane glycoprotein 2b, GE-11 peptide, lymphocyte function-associated...…”

“… Membrane derivation Excipient of nanoparticle Model drug Targeted cell line Ref. RBC Methoxy poly(ethylene glycol)- block -poly(D,L-lactide) PTX, TPC HeLa [60] Cancer cell PLGA DOX, Hb MCF-7 [70] PLGA R837 RM-1 [68] WBC PLGA DOX MCF-7 [84] Bismuth selenide QE 4T1 [90] Dual-end PEGylation of poly(β-amino ester) PTX MDA-MB-231 [91] PLGA PTX MKN-45 [93] Lipids 1,2-dioleoyl-sn‑glycero-3-phosphoethanolamine (DOPE), 1,2-dioleoyl-3-trimethylammonium-propane (chloride salt) (DOTAP), cholesterol DOX MCF-7 [96] PLGA CFZ 4T1 [103] Platelet Acrylamide, N -(3-aminopropyl) methacrylamide, glycerol dimethacrylate TRAIL, DOX MDA-MB-231 [107] Mesenchymal stem cell PLGA DOX MHCC97H [112] Bacteria Selenium-PEI siRNA HepG2 [119] − siRNA HCC-1954 [120] Exosome Transferrin DOX H22 …”