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. 2024 Apr 2;17:16. doi: 10.1186/s13045-024-01535-8

Table 1.

Nanoparticle-induced cancer immunotherapy through targeting macrophages

Nanoparticle Cancer type/Cell line Size (nm)/Zeta potential (mV) Outcome Reference
PEGylated liposomes

Breast cancer/4T1 cells

Pancreatic cancer/ murine KPC1245 and KPC1242 cells

75 nm

Delivery of mannose and levamisole hydrochloride for glycolysis suppression and reducing mitochondrial energy metabolism

Suppression of cancer proliferation

Combination with radiotherapy impairs M2 polarization of macrophages and increases immune responses

[260]
Prodrug nanoparticles

Colorectal cancer/MC38 cells

Breast cancer/MCF-7 cells

39 nm/-8.23 mV

263.2 nm/less than − 5 mV

Co-delivery of doxorubicin and R848

Modification of nanoparticles with bifunctional PD-1/PD-L1 peptide antagonist PCP

Cleavage of nanoparticles with FAP-α in the tumor stroma

Release of cargo in the tumor site stimulates immunogenic cell death and causes macrophage reprogramming

[261]
Lipid nanoparticles Pancreatic cancer/KPC cells 122.4 nm/+27.82 mV

Loading lipid nanoparticles in injectable hydrogels

Delivery of CCL5-siRNA by lipid nanoparticles to induce M1 polarization of macrophages and enhance T cell-induced immune responses

[262]
Upconversion nanostructures Breast cancer/4T1 cells 39.5 ± 1.1 and 54.1 ± 1.3 nm/-19.7 mV and − 4.1 mV

Introduction of upconversion nanoparticles co-doped with perfluorocarbon (PFC)/chlorin e6 (Ce6)

Targeted delivery of paclitaxel as a chemotherapy drug

Increasing singlet oxygen production

Stimulating M1 polarization of macrophage in accelerating pro-inflammatory cytokine release to impair breast cancer progression

[263]
Iron-chelated melanin-like nanocarriers Colon and breast cancers/ CT26 and 4T1 cells 150 nm Stimulating M1 polarization of macrophages and providing photothermal therapy, they accelerated tumor-associated antigen release to improve cancer immunotherapy [264]
Supramolecular nanoparticles Breast cancer/4T1 cells 190.1 nm/-17.1 mV Suppression of CSF1R and MAPK to stimulate M1 polarization of macrophages [265]
MIP-3β plasmid Breast cancer/4T1 cells 90 nm/-2.1 mV Increasing dendritic cell maturation and suppressing M2 polarization of macrophages [266]
Au@PG nanocarriers Lung cancer/ Lewis lung carcinoma cells 32.2 nm at 2.5 mM ONPG, 29.8 nm at 10 mM, 26.4 nm at 50 mM, and 18.3 nm at 75 mM

Polyaniline-based glycol-condensation on the nanostructures

Switching M2 polarized macrophages into M1 polarized macrophages

Nanoparticles with smaller sizes demonstrate higher efficacy in the macrophage re-education

[267]
CaCO3-loaded Au nanostructures Macrophages/RAW 264.7 cells 32 nm

Elongating macrophage cell morphology

Stimulation of M1 biomarker and inflammatory cytokines

Inducing M2 polarization of macrophages

[268]
Polymeric nanocarriers Osteosarcoma/K7M2 cells 98.4 nm/-14.3 mV

Biodegradable nanoparticles for delivery of regorafenib as vascular normalization compound

Release of cargo upon laser irradiation of 808 nm and increasing hypoxia in TME

Induction of the release of reactive oxygen species and mediation of immunogenic cell death

Stimulation of M1 polarization of macrophages

[269]
Gadofullerene nanocarriers Breast cancer/4T1 cells 68.1 nm/-37.7 mV M1 polarization of macrophages and increasing infiltration of T lymphocytes in the TME for cancer suppression [270]
DGL-ZA nanoparticles Breast cancer/4T1 cells 123.1 nm/-13.4 mV

Potential cancer biodistribution, extravasation, and high tumor penetration

Conjugation of dendrigraft poly-L-lysines as inducers of autophagy

Macrophage regulation and increasing tumor-suppressor activity

[271]
Phosphatidylserine-modified nanoparticles Melanoma/B16F10 cells 230 nm/at a range of 20–30 mV

Externalization of nanostructures occurs when they are exposed to the TME with upregulation of MMP2

Increasing depletion of tumular-associated macrophages in TME

[272]
Hyaluronic acid-functionalized nanoparticles Non-small cell lung cancer 92 nm/-12 mV Targeted delivery of miR-125b and increasing its transfection more than 6 times to induce M1 polarization and enhance iNOS levels [273]
Trimethyl chitosan nanoparticles Breast cancer/4T1 cells 120–160 nm/20 mV

Functionalization with mannose and glycocholic acid

Delivery of SIRPα-siRNA and MUC1 pDNA

Oral delivery of cargo

pMUC1 increases macrophage phagocytosis ability and M1 polarization

Increasing immunity by the SIRPα-siRNA

[274]