Immunotherapy-based novel nanoparticles in the treatment of gastrointestinal cancer: Trends and challenges

Table 1 Overview of immunotherapy-based novel nanoparticles in the treatment of gastric cancer [PubMed Search (immunotherapy) AND (nanoparticle) AND (gastric cancer)]

Type of nanoparticle	Treatment strategy	Drugs or active substance involved	The main involvement of immune cells	Ref.
Copolymers	ICIs, chemotherapy	DOC, PD-L1 mAb	T cells	Xu et al[50]
Copolymers	ICIs, epigenetic treatment	DAC, nivolumab	PD1+CD8+ TILs	Hu et al[52]
Hollow mesoporous organosilica nanoparticles	Dual-damage to nDNA and mitoDNA activates the c-GAS/STING pathway to stimulate innate immunity	Platinum, IR820	CD8+ T cells, DCs	Guo et al[54]
HSA nanoparticles	Targeted chemotherapy and immunotherapy	Au(III) thiosemicarbazone agent	TAMs	Zhang et al[57]
Polymers	DC vaccine	Human gastric tumor antigens	DCs	Kohnepoushi et al[61]
Gold nanoshell	Gene therapy, hyperthermia and immunoadjuvants therapy	HER-2 targeted siRNA, gold, CpG	DCs, T cells	Zhang et al[64]

ICIs: Immune checkpoint inhibitors; DOC: Docetaxel; PD-L1: Programmed cell death ligand 1; mAb: Monoclonal antibody; DAC: 5-Aza-20-deoxycytidine; TILs: Tumor-infiltrating T cells; DCs: Dendritic cells; HSA: Human serum albumin; TAMs: Tumor-associated macrophages; HER-2: Human epidermal growth factor receptor-2; CpG: Cytosine–guanine.

Table 2 Overview of Immunotherapy-based novel nanoparticles in the treatment of hepatocellular carcinoma [PubMed Search (immunotherapy) AND (nanoparticle) AND (hepatocellular carcinoma)]

Type of nanoparticle	Treatment strategy	Drugs or active substance involved	The main involvement of immune cells	Ref.
Nano-micelles	ICD, chemotherapy, PDT	PTX, TPABDTO	CTLs, MDSCs, Tregs, DCs	Xu et al[75]
Polymers	p53 gene reprograms the immune microenvironment	p53 mRNA	T cells, NK cells	Xiao et al[83]
MSNPs	Anti-angiogenic drugs, ICIs	Sorafenib, PD-L1 antibody	T cells	Li et al[84]
Copolymers	ICD, chemotherapy	Icaritin, DOX	T cells, DCs	Yu et al[85]
Lipid nanoparticle	CCL2 and CCL5 dual-target	BisCCL2/5i mRNA	TAMs	Wang et al[87]
Microcapsules	Improving hypoxia	Oxygen	TAMs	Dai et al[91]
Copolymers	Mitigates LSEC capillarization	Simvastatin	NKT cells	Yu et al[93]
LNPs	Antigen specific vaccine	Tumor-derived RNA	T cells, DCs	Zhang et al[98]

ICD: Immunogenic cell death; PDT: Photodynamic therapy; CTLs: Cytotoxic T lymphocytes; PTX: Paclitaxel; MDSCs: Myeloid-derived suppressor cells; DCs: Dendritic cells; CCL2: Chemokine C-C motif ligand 2; CCL5: Chemokine C-C motif ligand 5; DOX: Doxorubicin; PD-L1: Programmed cell death ligand 1; NK cells: Natural killer cells; TAMs: Tumor-associated macrophages; Tregs: Regulatory T lymphocytes; MSNPs: Mesoporous silica nanoparticles; LSEC: Liver sinusoidal endothelial cells; LNPs: Lipid nanoparticles; NKT: Natural killer T.

Table 3 Overview of Immunotherapy-based novel nanoparticles in the treatment of colorectal cancer [PubMed Search (immunotherapy) AND (nanoparticle) AND (colorectal cancer)]

Type of nanoparticle	Treatment strategy	Drugs or active substance involved	The main involvement of immune cells	Ref.
Copolymers	PDT induces HIF-1α expression, leading to the upregulation of PD-L1 expression, ICIs	Photosensitizer, PD-L1 antibody	DCs, CD8+T cells, memory T cells	Yuan et al[107]
Polymeric nanoparticle	PTT, chemotherapy, ICD	PBOXA, donor–spacer–acceptor–spacer–donor type fluorophore	DCs, T cells, CTLs	Zhu et al[108]
Copolymers	ICD, ICIs	SK, PD-L1 knockdown siRNA	DCs, TAMs, Tregs, T cells	Li et al[109]
Polymers	ICD, ferroptosis	DHA	DCs, T cells	Duan et al[111]
Platelet membrane-coated nanoparticle	TLR7 treatment	R848	DCs	Bahmani et al[113]
Liposomes with cell membrane	ICD, chemotherapy, lncRNA-targeting therapy	Oxaliplatin, shPvt1	DCs, MDSCs, CD8+T cells	Liu et al[117]
Silver nanoparticles	Anti-Fn	Phage M13	MDSCs, DCs, TAMs	Dong et al[122]
Supramolecular assembled programmable immune activation nanomedicine	In-situ cancer vaccine, ICD	PPCD, CpG/PAMAM	DCs, CD8+T cells	Zhang et al[123]

ICIs: Immune checkpoint inhibitors; HIF-1α: Hypoxia-inducible factor 1α; PDT: Photodynamic therapy; PTT: Photothermal therapy; ICD: Immunogenic cell death; PD-L1: Programmed cell death ligand 1; PBOXA: Oxaliplatin prodrug; SK: Shikonin, DHA: Dihydroartemisinin; TLR: Toll-like receptor; shPvt1: Short hair-pinned RNA against Pvt1; Fn: Fusobacterium nucleatum; PPCD: Poly-[(N-2-hydroxyethyl)-aspartamide]-Pt(IV)/beta-cyclodextrin; PAMAM: Polyamidoamine; MDSCs: Myeloid-derived suppressor cells; DCs: Dendritic cells; CTLs: Cytotoxic T lymphocytes; TAMs: Tumor-associated macrophages; Tregs: Regulatory T lymphocytes; MDSCs: Myeloid-derived suppressor cells.

Table 4 Overview of Immunotherapy-based novel nanoparticles in the treatment of pancreatic cancer [PubMed Search (immunotherapy) AND (nanoparticle) AND (pancreatic cancer)]

Type of nanoparticle	Treatment strategy	Drugs or active substance involved	The main involvement of immune cells	Ref.
Clustered nanoparticle	ICIs, TGF-β receptor inhibitors	LY2157299, siPD-L1	T cells	Wang et al[133]
HAS-Liposomes	ICD, ICIs, PTT	BMS-202, IR780	DCs, CTLs, T cells	Yu et al[134]
Copolymers	ICIs	siPD-L1	CD8+T cells, NK cells	Jung et al[138]
LNPs	STING and TLR4 therapy	STING agonist, R4 agonist	DCs, Tregs, TAMs	Lorkowski et al[139]
Micellar nanoparticle	Inhibit G-MDSCs recruitment, chemotherapy	LMWH, PTX	G-MDSC, CD8+T cells, CD4+T cells	Lu et al[142]
UCNPs	Pyroptosis	K3ZrF7:Yb/Er UCNPs	DCs, memory T cells	Ding et al[148]
Cancer cell membrane with copolymers	ICIs, M2-macrophages targeting	M2pep, TAAs, PD-L1 antibody	TAMs, CD8+T cells	Wang et al[151]
PDSA-based nanoplatform	Suppression of FFAs, repolarization of TAMs	siMGLL, siCB-2	TAMs	Cao et al[152]
Copolymers	PTT, immunotherapy	ICG, IMQ, IONs	TAMs, CD8+T cells, CD4+T cells, CD4+T cells	Wang et al[153]
IONs	Repolarization of TAMs	Ferumoxytol	TAMs	Zanganeh et al[154]

ICIs: Immune checkpoint inhibitors; PD-L1: Programmed cell death ligand 1; TGF-β: Transforming growth factor-β; ICD: Immunogenic cell death; DCs: Dendritic cells; STING: Stimulator of interferon genes; LMWH: Low molecular weight heparin; MDSCs: Myeloid-derived suppressor cells; G-MDSCs: Granulocytic myeloid-derived suppressor cells; UCNPs: Upconversion nanoparticles; M2pep: Peptides targeting M2-like macrophages; TAAs: Tumor-associated antigens; PDSA: Poly (disulfide amide); FFAs: Free fatty acids; siMGLL: MGLL siRNA; siCB-2: CB-2 siRNA; ICG Indocyanine green; IMQ: Imiquimod; IONs: Iron oxide nanoparticles; PTX: Paclitaxel; PTT: Photothermal therapy; TAMs: Tumor-associated macrophages; Tregs: Regulatory T lymphocytes; TLR: Toll-like receptor.