Table 1 Nanomaterials developed for termination of macrophage recruitment, TAMs depletion, and TAMs repolarization

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]