Nanoparticles from Cuttlefish Ink Inhibit Tumor Growth by Synergizing Immunotherapy and Photothermal Therapy

Abstract

Natural nanoparticles have been extensively studied due to their diverse properties and easy accessibility. Here, the nanoparticles extracted from cuttlefish ink (CINPs) with significant antitumor efficacy are explored. These CINPs, with spherical morphology, good dispersibility, and biocompatibility, are rich in melanin and contain a variety of amino acids and monosaccharides. Through the activation of mitogen-activated protein kinase (MAPK) signaling pathway, CINPs can efficiently reprogram tumor-associated macrophages (TAMs) from immune-suppressive M2-like phenotype to antitumor M1-like phenotype. Besides, under near-infrared (NIR) irradiation, CINPs exhibit high photothermal effect and tumor cell killing ability, which make them a potential candidate in photothermal therapy (PTT) of tumor. In vivo, CINPs can increase the proportion of M1 macrophages and foster the recruitment of cytotoxic T lymphocytes (CTLs) to tumors, leading to reduced primary tumor growth and lung metastasis. In combination with their photothermal effect, which can induce tumor-specific antigens release, CINPs could almost completely inhibit tumor growth accompanied by more active immune responses. Collectively, these CINPs described here can provide both tumor immunotherapy and PTT, implying that CINPs are promising for tumor treatment.

Platelet Membrane‐Camouflaged Magnetic Nanoparticles for Ferroptosis‐Enhanced Cancer Immunotherapy

“…Among the protein sets, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the most represented processes included tumor necrosis factor (TNF) signaling pathway, mitogen‐activated protein kinase (MAPK) signaling pathway, interleukin 17 (IL‐17) signaling pathway, and chemokine signaling pathway (Figure 7e), which are important pathways of immune system activation. [ 48 ] Particularly, in the protein sets belonged to MAPK signaling pathway, we found that the nuclear factor NF‐kappa‐B family proteins (Nfkb1 and Nfkb2), which play a key role in promoting M1 polarization, [ 49 ] significantly upregulated in response to Fe 3 O 4 ‐SAS@PLT treatment, suggesting that Fe 3 O 4 ‐SAS@PLT treatment might repolarize immunosuppressive M2 macrophages toward the antitumor M1 phenotype.…”

Bio-Applications of Multifunctional Melanin Nanoparticles: From Nanomedicine to Nanocosmetics

“…As result, the synergistic therapy could effectively reverse the immunosuppressive tumor microenvironment and significantly control tumor growth in multiple tumor models in mice, extend survival rate and further protect them against malignant metastasis in late stage breast cancer. A similar approach, but based on the use of natural melanin-containing cuttlefish ink nanoparticles (CINPs), was followed by Deng et al who demonstrated an efficient synergistic PTT-immunotherapeutic approach for tumor growth inhibition [181]. In particular, CINPs reach in melanin, containing also various amino acids and monosaccharides, were extracted from the ink sac of cuttlefish using a differential centrifugation method (Figure 13).…”

Melanin‐Like Nanomaterials for Advanced Biomedical Applications: A Versatile Platform with Extraordinary Promise

“…Very recently, cuttlefish ink sac extracted nanoparticles (CINPs) comprising melanin, amino acids, and monosaccharides were obtained using a straightforward differential centrifugation method, and their antitumor efficacy by synergizing immunotherapy and PTT were investigated ( Figure ) 103. The polysaccharides from CINPs could facilitate the repolarization of tumor‐associated macrophages toward anti‐tumor M1‐like phenotype and motivate the infiltration of cytotoxic T cells within the tumor in vivo.…”

“…* p < 0.05, ** p < 0.01, *** p < 0.001. Reproduced with permission 103. Copyright 2019, American Chemical Society.…”