Table 1.
Nanomaterials developed for termination of macrophage recruitment, TAMs depletion, and TAMs repolarization
| Cancers/cell lines | Strategy | Active target | Nanomaterial type | Drug | Diameter (nm) | Zeta Potential (mV) | Combination partner(s) | Outcome | Ref. |
|---|---|---|---|---|---|---|---|---|---|
| Breast cancer cell line (4 T1) | Termination of macrophage recruitment | CCR2 | Cationic nanoparticle (CNP) | CNP-siCCR2 | 120.9 ± 12.2–128.3 ± 18.1 | 2.7–25.2 | – | Blocking CCL2-CCR2 axis inhibited tumor growth and metastasis | [127] |
| Melanoma cell line (B16F10) | KLAK-MCP-1 micelles | KLAKLAK peptides | 11.9 ± 2.3 | 7.2 ± 1.1 | – | Inhibited the tumor growth via inhibiting the infiltration of TAMs and increasing the number of cytotoxic T-lymphocyte | [128] | ||
| Pancreatic ductal adenocarcinoma (THP1) | Copper nanoparticles Cu@CuO | Gemcitabine | 4.9 ± 0.3 | −4.8 ± 2.4 | – | Induced tumor necrosis, and ultimately suppressed the tumor growth and prolong the survival in PDAC tumors | [129] | ||
| Colon cancer (SL4) | CX3CL1 | 7C1 nanoparticles | DC101/ anti-Ly6G antibody | – | – | 7C1-Axo-siCX3CL1 | Reduced the expression of CX3CL1 and prevent the recruitment of macrophages in the tumor region | [130] | |
| Breast cancer cell line (4 T1)/ Colon cancer (CT26)/Melanoma (B16) | TAM depletion | CSF-1R | Sensitive cluster nanoparticles (BLZ-945SCNs/Pt) | BLZ-945 | – | – | Platinum (Pt)- | Depleted TAMs, inhibited tumor growth and metastasis by increasing the infiltration of CD8+ cytotoxic T-cells | [131] |
| Melanoma cell line (B16) | M2NPs | CSF-1R siRNA | – | – | M2 macrophage binding peptide | Depleted M2-like TAMs which restored the function of T-cells and inhibit the tumor growth | [132] | ||
| Breast cancer cell line (4 T1) | Dextran-grafted-copolymer (DH@ECm) | BLZ945 | ~ 190 | − 20.3 | – | Depleted TAMs which reverse the TME with increased infiltration of CD8+ cells and inhibit the tumor growth | [133] | ||
| Bone marrow derived macrophages (BMDMs) | – | CA4 nanoparticles (A15-BLZ-NP) | 163.4 | −20.3 | Activated anti-tumor immune response which results in improved inhibition of tumor growth | [134] | |||
| Breast cancer cell lines (4 T1, CT26, 3 T3, and RAW264.7) | Hypoxia | Calcium bisphosphonate derived nanoparticles (CaBP-PEG-NP) | – | 50 | −0.5 | – | Deplete TAMs, normalize vascular system, reduce angiogenesis, which leads to reduction in hypoxia and inhibition of tumor growth | [135] | |
| Sarcoma cell line (S180) | – | Lipid-coated calcium zoledronate nanoparticles (CaZol@pMNP) | – | 85 | Neutral | – | TAMs depletion, reduce angiogenesis and inhibit immune suppression to inhibit tumor growth | [136] | |
| Breast cancer cell line (4 T1) | – | Mannosylated mixed micelles (DAS-MMic) | Dasatinib | 21.55 ± 0.85 | – | TAMs depletion, decreased angiogenesis, remodel immunosuppressive TME and inhibit tumor growth | [137] | ||
| Melanoma cell line (B16F10) | MMP-2 | Phosphatidylserine nanoparticles (PS-NP) | 130–230 | Negative | – | TAMs depletion | [138] | ||
| Murine breast cancer cell line 4 T1 | PEG liposomes (PEG-FA-Lip) | Doxorubicin | 138.5 ± 6.8 | −9.3 ± 0.8 | – | Decreased infiltration of Treg cells to tumor sites, deplete the M2-like TAMs | [139] | ||
| Melanoma cell line (B16F10) |
Hyaluronic acid-gold Nanorods (HA-AuNR/M2pep-NP) |
– | 42.93–64.6 | – | Photothermal therapy | Eliminated M2-like TAMs, induce ICD to efficiently suppresses the tumor growth and prolongs the survival | [140] | ||
| Breast cancer cell line (4 T1) | IL-10/TGF-β/VEGF | Zoledronic acid nanorods (ZGd-NRs) | Zoledronic acid, | 100–200 | 15.43 | Radiotherapy | Improved dendritic cell maturation, promoted CD8+ T cell infiltration, and boosted the immune responses | [141] | |
| Lung cancer (SCLC, KP1) | Repolarization of M2 to M1 | – | Iron oxide nanoparticles (Ferumoxytol) | – | 15–40 | – | – | Prevented development of liver metastasis polarize M2-type to M1-type macrophages, | [27] |
| Melanoma cell lines(B16-F10) | Membrane-coated Fe3O4 nanoparticle (MNP@MDSC) | – | 85–100 | −18 − − 13 | Photothermal therapy | Reprograming M2-like to M1-like macrophages, reduced tumor’s metabolic activity and induce immunologic cell death | [142] | ||
| Colorectal cancer cell line (CT26)/ Breast cancer cell line (4 T1) | Iron-chelated melanin-like nanoparticles Fe@PDA-PEG) | ~ 150 | – | – | Recruitment of M1 macrophages and attracting T-helper cells and effector cells to the tumor site to inhibit the tumor growth | [143] | |||
| Colorectal cancer cell line (MC38) | TLRs | Cyclodextrin nanoparticles (CDNP) | R848 | 30 | 0.90 ± 1.90 | anti-PD-1 | Shifted toward M1 phenotype and inhibit tumor growth and potentiate the efficacy of anti-tumor immune response of anti-PD-1 | [144] | |
| 39 ± 1.8 | 6.61 ± 1.03 | – | Reprogramming of TAMs towards anti-tumor M1 phenotype | [145] | |||||
| Breast cancer cell line (4 T1) | CpG- oligodeoxynucleotides ferritin Nano-cages (CpG-ODNs) | – | 20.24 ± 0.29 | − 11.77 ± 0.40 | – | Repolarized TAMs to the M1-like in vitro and in vivo, and reduced tumor development in 4 T1 tumor-bearing animal model | [146] | ||
| Murine Melanoma B16 OVA | PLGA nanoparticles (PNP@R@M-T-NP) | R848 | 188 | −9.7 | – | Repolarize M2 to M1-type, reduce tumor size and prolong animal survival | [28] | ||
| LLC Ova cell line | Nanobodies | Imidazoquinoline | – | – | anti-PD1 | Reduced the tumor growth and increased anti-tumor T-cell response by repolarizing TAMs towards pro-inflammatory phenotype | [147] | ||
| Breast cancer cell line (4 T1) | IRF5 and NF-κB signaling | Polymer magnetic nanocarrier (PLGA-ION-R837@M) | R837 | 166.2 ± 1.8 | −19.1 ± 0.1. | – | enhanced TAMs repolarization which relieve immunosuppressive TME to activate the anti-tumor immune response | [148] | |
| lymphoma cell lines (Raji) epidermoid carcinoma cell line (A-431) and breast cancer cell line (SKBR3) | Phagocytosis | Liposome (R848-LPs) | R848 | 141.9 ± 57.7 | −23.9 ± 6.0 | Rituximab/ Trastuzumab/ anti-EGFR mouse monoclonal antibody | Reprogram TAMs to M1-type macrophages | [149] | |
| Breast cancer cell line (4 T1) | CD47-SIRPα | Exosome nano bioconjugates | aCD47 & aSIRPα | 20 | – | – | Repolarize pro-tumor M2 to anti-tumor M1 macrophages, block SIRPα & CD47, improve phagocytosis | [150] | |
| Breast cancer cell line (4 T1) | Cell membrane-coated magnetic nanoparticles (gCM-MNs) | – | 100 | −19 | – | Repolarization of M2-type to M1-type macrophages | [151] | ||
| Melanoma cell line (B16F10) | Calcium carbonate nanoparticles (CaCO3) | CD47 antibody | 100 | – | – | Activation of M1-type macrophages, inhibit local tumor recurrence and metastasis post-surgery | [152] | ||
| Breast cancer cell line (4 T1) | NF-κβ signaling pathway | Hyaluronic acid- superparamagnetic iron oxide nanoparticles (HIONs) | – | – | – | – | Reprogram M2-TAMs to antitumor M1 | [153] | |
| Breast cancer cell line (MDA-MB-231) | PI3K signaling pathway | Porous hollow iron oxide nanoparticles (PHNPs@DPA-S-S-BSA-MA@3MA) | 3-methyladenine | 20 | −14.8 − 19.7 | – | Repolarization of M2-type to M1-type macrophages and activate the immune cell population of CD8+ and CD4+ T-cells, B-cell, NK cells and Treg cells | [154] | |
| Cervical cancer cell line (Hela) Lung carcinoma (LLC) | Lactate oxidase and glycolysis pathway | Hollow MnO2 | lactate oxidase and glycolysis inhibitor | 3.4 | −20 | Anti-PD-L1 | Reduced lactic acid production and reduced population of M2-type macrophages | [155] | |
| Hepato cellular carcinoma (JHH-7/HCA-1) | Angiogenesis | Nanocarrier (NanoMnSor) | Sorafenib | 136.2 ± 1.0 | −30 | Anti-PD-1 antibody | Macrophage towards immunostimulatory M1 macrophages and increases the CD8+ cytotoxic T-cells in tumors | [156] | |
| Melanoma (B16F10) | NF-κβ signaling pathway | Copper sulfide nanoparticles (CuS-NP) | – | 17 | – | – | Direct BMDM polarization towards anti-tumor M1-phenotype, remodels TME, prolong median survival | [157] | |
| Hepatocellular carcinoma cell line (Hepa1–6 cells) | Repolarization of M2 to M1 | – | Lipid nanoparticles (M1/SLNPs) | Sorafenib | – | – | – | Increased ratio of M1-type macrophages as compared to M2-type and inhibit the tumor growth | [158] |
| Hepatocellular carcinoma cells (HepG2) | NKG2D activation | Selenium nanoparticles (SeNPs) | Cytokine-induced killer cell immunotherapy | 102 ± 9.6 | 153.4 | – | Promoting M2 to anti-tumor M1 macrophages and increase the infiltration of natural killer cells to tumors | [159] | |
| Renal cell carcinoma cell line (OS-RC-2) | STAT3/hypoxia inducible factor-1 (HIF-1α) | Lipid nanoparticles formulations (LNPs) | siRNA STAT3/ HIF-1 α | 90–100 | 0.21 ± 0.63 | – | Increased infiltration of Mφ (CD11b + cells) into the TME and increased level of M1-type macrophages, | [160] | |
| Breast cancer cell line (PyMT-Bo1, MFI 17)/ melanoma (MDA.MB.435, MFI 27) and endothelial (HUVEC, MFI 42) cell lines | MYC pathway | Perfluorocarbon nanoparticles | MI3-PD | 262 | −20 | αvβ3 antagonist | Decreased M2 macrophages in the TME without sparing M1-type | [161] | |
| Breast cancer cell line (4 T1)/Melanoma cell lines (B16/F10) | CSF-1R and Src homology-region 2 (SHP-2) | Supramolecular nanoparticles | BLZ-945 | 143 ± 34 | 7.9 | SHP099/ DNT206 | Reprogramming of M2-type macrophages to anti-tumor M1-type | [162] | |
| Breast cancer cell line (4 T1) | CSF-1R and MAPK pathways | 190.1 ± 27 | −17.1 ± 7.3 | Selumetinib | Repolarize M2 macrophages to an anti-tumorigenic M1 phenotype | [163] | |||
| Hepatocellular carcinoma (Hepa1–6)/Pancreatic cancer (KPC) | CCL2/5 signaling pathways | BisCCL2/5i mRNA | 100–120 | – | PD-L1 | TAMs polarization towards the anti-tumoral M1 phenotype and long-term survival | [164] | ||
| Breast cancer cell line (4 T1) | Macrophage Inflammatory Protein 3 Beta (MIP-3β) | Nanoparticles (3-trimethylammonium-propane (DOTAP), Methoxy poly (ethylene glycol)-poly(lactide) (MPEG-PLA), and folic acid modified poly (ethylene glycol)-poly(ε-caprolactone) | – | 90 | −2.1 | – | Polarization of macrophages towards M1 polarization, inhibit the tumor growth and metastasis | [165] | |
| Melanoma cell lines(B16/F10) | Repolarization of M2 to M1 | – | ZnO and gold nanoparticles (AuNP@mSiO2@Dox-ZnO) | Doxorubicin | 27–72 | – | Photothermal treatment | Toxicity to cancer cells and contribute in immunogenic cell death, prevent tumor growth and metastasis | [166] |
| - (RAW 264.7 cells) | – | Gold nanoparticles encapsulated CaCO3 (Au@CaCO3-NP) | – | 32 | – | – | Direct repolarization of M2 macrophages towards M1-type | [167] | |
| Osteosarcoma (MG63)/Colorectal carcinoma (HCT116)/Breast cancer (MCF7) cell lines | – | Hyaluronic acid-dexamethasone micelles (HA-DEX-DOX) | Dexmethasone & Doxorubicin | ~ 252 | −23 − − 26 | – | M2-macrophages towards pro-inflammatory M1-type phenotype, encourage Dox-mediated apoptosis | [168] | |
| Melanoma cell line (B16) | – | PLGA nanoparticles | Baicalin | 97.2–123.6 | −43.1 ± 0.4/ -17.8 ± 0.3 | Hgp | Transformation of M2-like TAMs to M1-like, suppress tumor angiogenesis, inhibited metastasis, stimulate NK cell infiltration | [169] | |
| Colorectal cancer (CT26-FL3), Pancreatic (PDAC) and breast cancer (4 T1) cell lines | – | Lipid calcium phosphate nanoparticles (LCP) | – | 189.5 | −6.82 | PD-L1 | Inhibited the metastasis and shifted the immunosuppressive TME towards immunostimulatory stage with better cytotoxic T-cell infiltration, which results in prolong animal survival | [170] | |
| Breast cancer cell line (4 T1) | – | Polymer nanoparticles (P-NPs) | – | 45 | −25 | Photodynamic Therapy | Shifts macrophages towards anti-tumorous phenotype, reverse TME and inhibit the tumor growth | [171] | |
| Breast cancer cell line (4 T1) or human pulmonary carcinoma cell line (A549) | NF-κB and IRF5 pathways | Gadofullerene nanoparticles (Gd@C82) | – | ~ 55 | −37.7 ± − 0.3 | PD-L1 | Reprogram M2 to M1, induce infiltration of cytotoxic T-lymphocytes and inhibit the tumor growth, promotes efficacy of PD-L1 | [172] | |
| Desmoplastic Melanoma (BPD6). | Liposomes | Hydralazine Doxorubicin | 88 ± 4 | −1.8 | – | Repolarize the TAMs by normalizing tumor blood vessels, effectively inhibit melanoma growth | [173] | ||
| Melanoma cell line (A375) | Mitochondrial-mediated apoptosis pathway | Tellurium Nano stars (GTE-RGD) | – | 170 | 19.9 to + 19.6 | PD-1 & Radiotherapy | Increase M1 macrophages, potentiated radiotherapy, eradicate tumor, enhance cytotoxic T-lymphocytes | [174] | |
| Breast cancer (MCF-7) Renal cell carcinoma (A498)/Lung adenocarcinoma cell line (A549) | NF-κB and STAT3 pathways | TCCP-loaded mPEG-PLGA polymeric nanoparticles | – | 80 ± 1.5 | −11.8 ± − 0.8 | Photodynamic Therapy | Enhance polarization to M1 macrophages, induced immunogenic cell death, increase anti-tumor immunity of NK cells | [175] |