# Application of Nano-Delivery Systems in Lymph Nodes for Tumor Immunotherapy

**Authors:** Yiming Xia, Shunli Fu, Qingping Ma, Yongjun Liu, Na Zhang

PMC · DOI: 10.1007/s40820-023-01125-2 · 2023-06-03

## TL;DR

This paper reviews how nano-delivery systems can target lymph nodes to improve cancer immunotherapy by enhancing immune cell activation.

## Contribution

The paper systematically categorizes and reviews recent advances in nano-delivery systems for lymph node-targeted immunotherapy.

## Key findings

- Lymph nodes provide a unique microenvironment for immune cell activation and are key targets for immunotherapy.
- Nano-delivery systems improve drug accumulation in lymph nodes, enhancing anti-tumor immune responses.
- Factors influencing nano-carrier accumulation in lymph nodes are discussed to guide future delivery strategies.

## Abstract

The physiological structure and the drug delivery barriers of lymph nodes were described.The factors affecting lymph nodes accumulation in nano-delivery systems were discussed.The recent progress of nano-delivery carriers applied for lymph nodes immunotherapy was further categorized and reviewed.

The physiological structure and the drug delivery barriers of lymph nodes were described.

The factors affecting lymph nodes accumulation in nano-delivery systems were discussed.

The recent progress of nano-delivery carriers applied for lymph nodes immunotherapy was further categorized and reviewed.

Immunotherapy has become a promising research “hotspot” in cancer treatment. “Soldier” immune cells are not uniform throughout the body; they accumulate mostly in the immune organs such as the spleen and lymph nodes (LNs), etc. The unique structure of LNs provides the microenvironment suitable for the survival, activation, and proliferation of multiple types of immune cells. LNs play an important role in both the initiation of adaptive immunity and the generation of durable anti-tumor responses. Antigens taken up by antigen-presenting cells in peripheral tissues need to migrate with lymphatic fluid to LNs to activate the lymphocytes therein. Meanwhile, the accumulation and retaining of many immune functional compounds in LNs enhance their efficacy significantly. Therefore, LNs have become a key target for tumor immunotherapy. Unfortunately, the nonspecific distribution of the immune drugs in vivo greatly limits the activation and proliferation of immune cells, which leads to unsatisfactory anti-tumor effects. The efficient nano-delivery system to LNs is an effective strategy to maximize the efficacy of immune drugs. Nano-delivery systems have shown beneficial in improving biodistribution and enhancing accumulation in lymphoid tissues, exhibiting powerful and promising prospects for achieving effective delivery to LNs. Herein, the physiological structure and the delivery barriers of LNs were summarized and the factors affecting LNs accumulation were discussed thoroughly. Moreover, developments in nano-delivery systems were reviewed and the transformation prospects of LNs targeting nanocarriers were summarized and discussed.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Vcam1 (vascular cell adhesion molecule 1) [NCBI Gene 22329] {aka CD106, Vcam-1}, Scarb1 (scavenger receptor class B, member 1) [NCBI Gene 20778] {aka CD36, Cd36l1, Chohd1, Cla-1, Cla1, D5Ertd460e}, TLR7 (toll like receptor 7) [NCBI Gene 51284] {aka IMD74, SLEB17, TLR7-like}, Cgas (cyclic GMP-AMP synthase) [NCBI Gene 214763] {aka E330016A19Rik, Mb21d1}, Prox1 (prospero homeobox 1) [NCBI Gene 19130] {aka A230003G05Rik, PROX-1}, Clec7a (C-type lectin domain family 7, member a) [NCBI Gene 56644] {aka BGR, Clecsf12, beta-GR}, Sting1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 72512] {aka 2610307O08Rik, ERIS, MPYS, Mita, STING, STING-beta}, Ighv1-9 (immunoglobulin heavy variable 1-9) [NCBI Gene 668478] {aka Gm16697, Igg2a}, Ccr7 (C-C motif chemokine receptor 7) [NCBI Gene 12775] {aka CC-CKR-7, CCR-7, CD197, Cdw197, Cmkbr7, EBI1}, Cel (carboxyl ester lipase) [NCBI Gene 12613] {aka 1810036E18Rik, BAL, BSSL}, Pdcd1 (programmed cell death 1) [NCBI Gene 18566] {aka Ly101, PD-1, Pdc1}, Npepps (aminopeptidase puromycin sensitive) [NCBI Gene 19155] {aka AAP-S, MP100, Psa, goku}, Ly75 (lymphocyte antigen 75) [NCBI Gene 17076] {aka CD205, DEC-205, DEC205}, Alb (albumin) [NCBI Gene 11657] {aka Alb-1, Alb1, BCL001, BCL002, BPL001}, CD3E (CD3 epsilon subunit of T-cell receptor complex) [NCBI Gene 916] {aka CD3epsilon, IMD18, T3E, TCRE}, Eln (elastin) [NCBI Gene 13717] {aka E030024M20Rik}, Ackr4 (atypical chemokine receptor 4) [NCBI Gene 252837] {aka A630091E18Rik, CCBP2, CCR11, CCX-CKR, CCX-CKR1, Ccrl1}, Itgax (integrin alpha X) [NCBI Gene 16411] {aka Cd11c, Cr4, N418}, Nr1i3 (nuclear receptor subfamily 1, group I, member 3) [NCBI Gene 12355] {aka CAR, CAR-beta, Care2, ESTM32, MB67}, Nr3c2 (nuclear receptor subfamily 3, group C, member 2) [NCBI Gene 110784] {aka MR, Mlr}, CD28 (CD28 molecule) [NCBI Gene 940] {aka IMD123, Tp44}, Trp2 (tRNA proline 2) [NCBI Gene 104042] {aka Trp-2}, Tlr7 (toll-like receptor 7) [NCBI Gene 170743], Itgam (integrin alpha M) [NCBI Gene 16409] {aka CD11b/CD18, CR3, CR3A, Cd11b, F730045J24Rik, Ly-40}, Sell (selectin, lymphocyte) [NCBI Gene 20343] {aka CD62L, L-selectin, LAM-1, LECAM-1, LECAM1, Lnhr}, Tlr3 (toll-like receptor 3) [NCBI Gene 142980], Ctla4 (cytotoxic T-lymphocyte-associated protein 4) [NCBI Gene 12477] {aka Cd152, Ctla-4, Ly-56}, Clec9a (C-type lectin domain family 9, member a) [NCBI Gene 232414] {aka 9830005G06Rik, DNGR-1}, Csf2 (colony stimulating factor 2 (granulocyte-macrophage)) [NCBI Gene 12981] {aka CSF, Csfgm, GMCSF, Gm-CSf, MGI-IGM}
- **Diseases:** fungal infection (MESH:D009181), metastases of (MESH:D009362), melanoma (MESH:D008545), pancreatic, thyroid, and ovarian (MESH:D010051), lymphatic metastases (MESH:D008207), ICD (MESH:D003643), liver cancer (MESH:D006528), drug toxicity (MESH:D064420), HNSCC (MESH:D000077195), triMN-LPR (MESH:D015619), Tumor (MESH:D009369), prostate cancer (MESH:D011471), oral cancer (MESH:D009062)
- **Chemicals:** DAPI (MESH:C007293), menthol (MESH:D008610), ALC-0315 (MESH:C000712847), chitosan (MESH:D048271), glycol (MESH:D006018), CpG (MESH:C015772), ICG (MESH:D007208), ALG (MESH:D000464), furan (MESH:C039281), sucrose (MESH:D013395), MOFs (MESH:C040750), Ipilimumab (MESH:D000074324), azide (MESH:D001386), mannose (MESH:D008358), cholesterol (MESH:D002784), hyaluronic acid (MESH:D006820), thiol (MESH:D013438), dendritic polymers (MESH:D050091), DiD (MESH:D017878), GpG (MESH:C018309), silicon (MESH:D012825), Lipid (MESH:D008055), phosphate (MESH:D010710), R837 (MESH:D000077271), rapamycin (MESH:D020123), polydopamine (MESH:C568283), OH- (MESH:C031356), cyclophosphamide (MESH:D003520), anthracyclines (MESH:D018943), metal (MESH:D008670), PLGA (MESH:D000077182), biotin (MESH:D001710), F127 (MESH:C078661), Nivolumab (MESH:D000077594), mitoxantrone (MESH:D008942), DEX (MESH:D003915), PEG (MESH:D011092), phospholipid (MESH:D010743), silicol (MESH:C082343), paclitaxel (MESH:D017239), Polymer (MESH:D011108), oxaliplatin (MESH:D000077150), 1V209 (MESH:C000710667), peptides (MESH:D010455), dimethyl sulfoxide (MESH:D004121), chitin (MESH:D002686), silica (MESH:D012822), beta-glucan (MESH:D047071), PS (MESH:D010718), bortezomib (MESH:D000069286), CpG ODNs (MESH:C408982), PG (MESH:C043941), nitrogen (MESH:D009584), fluorescein (MESH:D019793), TDB (-), water (MESH:D014867), tamoxifen (MESH:D013629), SPIO (MESH:C000499), DDAB (MESH:C046112), ATP (MESH:D000255)
- **Species:** Simian-Human immunodeficiency virus (species) [taxon 57667], Metopion-like sp. (SA) (species) [taxon 188968], Mus musculus (house mouse, species) [taxon 10090], Ovis aries (domestic sheep, species) [taxon 9940], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Salmonella (genus) [taxon 590]
- **Mutations:** F127
- **Cell lines:** B16-OVA — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_WM78), MN-LPR — Homo sapiens (Human), Adult acute myelomonocytic leukemia, Transformed cell line (CVCL_WN74), RAW264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), B16F10 — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_0159), DC 2.4 — Mus musculus (Mouse), Transformed cell line (CVCL_J409)

## Figures

12 figures with captions in the complete paper: https://tomesphere.com/paper/PMC10239433/full.md

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Source: https://tomesphere.com/paper/PMC10239433