. Author manuscript; available in PMC: 2021 Nov 4.

Published in final edited form as: Drug Discov Today. 2021 Feb 19;26(6):1482–1489. doi: 10.1016/j.drudis.2021.02.017

Table 2. Nanomedicines targeting immune cells in tumor, blood, and immune cell-enriched organs.

Selected representative publications demonstrate the use of nanoparticles for immunomodulatory, nanoparticle-mediated transportation, and immune cell tracking purposes in cancer and inflammatory diseases.

	Nanoparticle	Targeting decoration	Payload	Payload function	Tissue target	Cell target	Major outcome	Ref.
1	PLGA-based polymeric micelle	CD8a PD-1	R848	TLR7/8 agonist	Tumor Blood Spleen LN	CD8⁺ T cell PD-1⁺ T cell	↑ survival ↑ tumor-infiltrating CD8⁺ T cells sensitizing tumors to anti-PD-1 therapy	[18]
1	PLGA-based polymeric micelle	CD8a PD-1	SD-208	TGF-β inhibitor	Tumor Blood Spleen LN	CD8⁺ T cell PD-1⁺ T cell		[18]
2	PLGA-lipid hybrid nanoparticle	tLyp1	Imatinib	Tyrosine kinase inhibitor	Tumor	FoxP3⁺ Treg cell	↑ survival ↑ tumor inhibition ↓ FoxP3⁺ Treg cell ↑ CD8⁺ T cell potentiated anti-CTLA-4 therapy	[19]
3	β-cyclodextrin nanoparticle	-	R848	TLR7/8 agonist	Tumor	M2 macrophage	polarized M2 → M1 macrophages controlled tumor growth protected against tumor re-challenge potentiated anti-PD-1 therapy	[20]
4	Liposome	CD206	BLZ945	CSF1R inhibitor	Tumor	M2 macrophage	polarized M2 → M1 macrophages ↑ phagocytic capabilities ↑ anti-tumor efficacy	[21]
4	Liposome	CD206	SHP099	SHP2 inhibitor	Tumor	M2 macrophage		[21]
5	Polymeric nanoparticle	CD206	IRF5 mRNA IKKβ mRNA	Encoding M1 macrophage polarization factors	Tumor	M2 macrophage	polarized M2 → M1 macrophages ↑ survival ↑ T cell infiltration control tumor metastases potential to reprogram human macrophages	[23]
6	Liposome Nanoemulsion	cRGD	(for imaging purposes)		Blood	Neutrophils Ly6C^- monocytes	nanoparticle hitchhiking with phagocytes in breast cancer	[24]
7	Liposome	cRGD	Edaravone	Neuroprotective	Blood	Neutrophils Monocytes	nanoparticle hitchhiking with phagocytes in cerebral ischemia ↓ infarcted volume	[26]
8	Polymeric nanoparticle Gold nanorod	CD11b	Pyropheophorbide-a (not loaded)	Photosensitizer	Blood	Neutrophils	↑ neutrophil tumor infiltration upon photosensitization ↑ survival ↓ tumor growth	[27]
9	Liposome	CD3 CD4 CD25 Ly6C	CD45 siRNA	(for testing CD45 silencing)	Blood LN	CD3⁺ T cells CD4⁺ T cells CD25⁺ Treg cells Ly6C⁺ monocytes	cell-specific siRNA delivery ↓ colitis by targeting Ly6C⁺ pro-inflammatory monocytes in an IBD model	[28]
9	Liposome	CD3 CD4 CD25 Ly6C	TNF siRNA	To inhibit the expression of the pro-inflammatory mediator TNFα	Blood LN	CD3⁺ T cells CD4⁺ T cells CD25⁺ Treg cells Ly6C⁺ monocytes		[28]
10	Liposome	Ly6C	IL10 modified mRNA	Expressing the antiinflammatory cytokine IL10	Spleen	Ly6C⁺ monocytes	↑ IL10 in liver, spleen, colon ↓ colitis by targeting Ly6C⁺ monocytes in an IBD model	[29]
11	HDL nanoformulation	-	(for imaging purposes)		Spleen BM Blood	Neutrophils Ly6C⁺ monocytes Ly6C^- monocytes	↑ infiltration of Ly6C⁺ monocytes in intermediate atherosclerosis ↑ infiltration of neutrophils in advanced stage atherosclerosis Recruitment of myeloid cells in myocardial infarction	[33]
12	Lipid nanoparticle	SORT molecules	hEPO mRNA or IL-10 mRNA	To verify the expression of hEPO and IL-10	Spleen Liver Lung	Macrophages B cells T cells others	Organ-specific targeting Effective mRNA expression in organ specific manner Effective gene editing in organ specific manner	[34]
			Cre mRNA	To activate tdTom expression
			Cas9 protein / sgTom1	To improve the delivery of Cas9 RNPs
			Cas9 mRNA / sgPTEN	To edit PTEN for anti-cancer purposes
			Cas9 mRNA / sgPCSK9	To edit PCSK9 for anti-atherosclerotic purposes
13	Lipid nanoparticle	-	gp100 mRNA TRP2 mRNA	Encoding tumor-associated antigens	LN	Dendritic cells Neutrophils Macrophages B cells	Successful anticancer vaccination ↑ cytotoxic CD8⁺ T cell response ↑ survival ↓ tumor growth	[43]
14	Polymeric micelle	-	Adpgk	peptide neoantigen	LN	Dendritic cells Macrophages	Successful anti-cancer vaccination ↑ cytotoxic CD8⁺ T cell response ↑ survival ↓ tumor growth Potentiating anti-PD-1 therapy	[45]
			R848	TLR7/8 agonist
			CpG	TLR9 agonist
15	Liposome	-	gp70 RNA	Encoding endogenous antigen of Moloney murine leukaemia virus	LN BM Spleen Lung	Dendritic cells	Activation of NK, T, B cells ↑ survival ↓ tumor growth Induction of systemic INFα in patients Priming and amplification of T cells against the antigens in patients	[46]
			OVA RNA	Encoding an ovalbumin epitope expressed in B16F10 cell line
			Hemagglutinin RNA	Encoding influenza virus hemagglutinin
			NY-ESO-1 RNA MAGE-A3 RNA tyrosinase RNA TPTE RNA	Encoding tumor antigens for clinical use
16	Polymer / lipid TransIT reagent	-	CD3 × CLDN6 mRNA CLDN18.2 × CD3 mRNA EpCAM × CD3 mRNA CD3 × (CLDN6)₂ mRNA	In vitro-transcribed mRNA encoding bispecific antibodies against T cells, cancer cells, epithelial cells	Liver	T cells	↑ plasma levels of bi-functional proteins Elimination of advanced xenograft tumors Activated T cells on cell-target specific manner ↑ cytotoxic T cells in tumors	[47]