# T cell-inspired therapeutic delivery platforms: From nanomedicines to cell therapy

**Authors:** Nasrullah Jan, Hassan Shah, Safiullah Khan, Naveed Ullah Khan, Yan Li, Xinwei Zhang, Guixiu Shi

PMC · DOI: 10.1016/j.mtbio.2026.102909 · 2026-02-10

## TL;DR

This review explores T cell-inspired delivery systems that improve drug targeting and reduce toxicity for treating various diseases.

## Contribution

A comprehensive review of T cell-inspired delivery platforms, highlighting their biocompatibility and therapeutic potential.

## Key findings

- T cell-inspired delivery systems offer prolonged circulation and targeted drug transport.
- These systems show reduced toxicity and improved biodistribution in various diseases.
- Current limitations and future engineering opportunities are discussed.

## Abstract

Targeted nanodrug delivery has garnered significant interest as a carrier for drugs, genes, and vaccines. Despite their clinical potential, these nanocarriers face substantial challenges due to their exogenous nature. These challenges can be addressed by employing T cell-inspired approaches for targeted therapies. T cell-inspired approaches—including T cell membrane-coated nanoparticles, T cell-derived exosomes, T cell hitchhiking, and chimeric antigen receptor (CAR)-T cells—exhibit remarkable properties such as inherent biocompatibility and biodegradability, prolonged circulation lifespan, and the ability to traverse biological barriers. Utilizing T cells as delivery vehicles enables prolonged circulation time and targeted drug transport, along with reduced toxicity to cells and tissues. This review explores innovative T cell-derived approaches, including T cell membrane-coated nanoparticles, T cell-derived exosomes, T cell hitchhiking, and CAR-T cells. We discuss how these methods improve biodistribution, tissue penetration, and immune evasion while preserving T cell functionality in cancer therapies, autoimmune disorders, cardiovascular diseases, and infectious diseases. By comparing conventional nanomedicine approaches with emerging T cell-based delivery systems, this review explores the transformative capability of T cell-inspired delivery in enhancing therapeutic outcomes. Finally, we address current limitations and future directions, including advanced engineering techniques, which could further refine this promising approaches.

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•Cell-based nanodelivery systems offer inherent biocompatibility, prolonged circulation, and targeted delivery.•T cell-inspired approaches, including membrane coating, exosomes, hitchhiking, and CAR-T cells are reviewed.•Applications of T cell-inspired approaches for various diseases are discussed, along with current limitations and future opportunities.

Cell-based nanodelivery systems offer inherent biocompatibility, prolonged circulation, and targeted delivery.

T cell-inspired approaches, including membrane coating, exosomes, hitchhiking, and CAR-T cells are reviewed.

Applications of T cell-inspired approaches for various diseases are discussed, along with current limitations and future opportunities.

## Linked entities

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

## Full-text entities

- **Genes:** ITIH4 (inter-alpha-trypsin inhibitor heavy chain 4) [NCBI Gene 3700] {aka GP120, H4P, IHRP, ITI-HC4, ITIHL1, PK-120}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, LAG3 (lymphocyte activating 3) [NCBI Gene 3902] {aka CD223}, CD7 (CD7 molecule) [NCBI Gene 924] {aka GP40, LEU-9, TP41, Tp40}, CD274 (CD274 molecule) [NCBI Gene 574058] {aka PDL1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD28 (CD28 molecule) [NCBI Gene 940] {aka IMD123, Tp44}, NOD2 (nucleotide binding oligomerization domain containing 2) [NCBI Gene 64127] {aka ACUG, BLAU, BLAUS, CARD15, CD, CLR16.3}, CD69 (CD69 molecule) [NCBI Gene 969] {aka AIM, BL-AC/P26, CLEC2C, EA1, GP32/28, MLR-3}, CCR5 (C-C motif chemokine receptor 5) [NCBI Gene 1234] {aka CC-CKR-5, CCCKR5, CCR-5, CD195, CKR-5, CKR5}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CD247 (CD247 molecule) [NCBI Gene 919] {aka CD3-ZETA, CD3H, CD3Q, CD3Z, CD3ZETA, IMD25}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CD5 (CD5 molecule) [NCBI Gene 921] {aka LEU1, T1}, CARS1 (cysteinyl-tRNA synthetase 1) [NCBI Gene 833] {aka CARS, CYSRS, MCDDBH, MDBH, MGC:11246}, CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, ITGAL (integrin subunit alpha L) [NCBI Gene 3683] {aka CD11A, EV6, HNA-5, LFA-1, LFA1A}, MUC1 (mucin 1, cell surface associated) [NCBI Gene 4582] {aka ADMCKD, ADMCKD1, ADTKD2, CA 15-3, CD227, Ca15-3}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, MS4A1 (membrane spanning 4-domains A1) [NCBI Gene 931] {aka B1, Bp35, CD20, CVID5, FMC7, LEU-16}, ITGAX (integrin subunit alpha X) [NCBI Gene 3687] {aka CD11C, SLEB6}, CXCR4 (C-X-C motif chemokine receptor 4) [NCBI Gene 7852] {aka CD184, D2S201E, FB22, HM89, HSY3RR, LCR1}, CD22 (CD22 molecule) [NCBI Gene 933] {aka SIGLEC-2, SIGLEC2}, Nr1i3 (nuclear receptor subfamily 1, group I, member 3) [NCBI Gene 12355] {aka CAR, CAR-beta, Care2, ESTM32, MB67}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, CLEC7A (C-type lectin domain containing 7A) [NCBI Gene 64581] {aka BGR, CANDF4, CD369, CLECSF12, DECTIN1, SCARE2}, TSG101 (tumor susceptibility 101) [NCBI Gene 7251] {aka TSG10, VPS23}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, CD81 (CD81 molecule) [NCBI Gene 975] {aka CVID6, S5.7, TAPA1, TSPAN28}, CAT (catalase) [NCBI Gene 397568], FGL1 (fibrinogen like 1) [NCBI Gene 2267] {aka HFREP1, HP-041, HPS, LFIRE-1, LFIRE1}, HAVCR2 (hepatitis A virus cellular receptor 2) [NCBI Gene 84868] {aka CD366, HAVcr-2, KIM-3, SPTCL, TIM3, TIMD-3}, FASLG (Fas ligand) [NCBI Gene 356] {aka ALPS1B, APT1LG1, APTL, CD178, CD95-L, CD95L}, PROM1 (prominin 1) [NCBI Gene 8842] {aka AC133, CD133, CORD12, MCDR2, MSTP061, PROML1}, NT5E (5'-nucleotidase ecto) [NCBI Gene 4907] {aka CALJA, CD73, E5NT, NT, NT5, NTE}, TNFRSF18 (TNF receptor superfamily member 18) [NCBI Gene 8784] {aka AITR, CD357, ENERGEN, GITR, GITR-D}, TNFRSF17 (TNF receptor superfamily member 17) [NCBI Gene 608] {aka BCM, BCMA, CD269, TNFRSF13A}, MSLN (mesothelin) [NCBI Gene 10232] {aka MPF, SMRP}, TNFRSF13C (TNF receptor superfamily member 13C) [NCBI Gene 115650] {aka BAFF-R, BAFFR, BROMIX, CD268, CVID4, prolixin}, CD63 (CD63 molecule) [NCBI Gene 967] {aka AD1, HOP-26, ME491, MLA1, OMA81H, Pltgp40}, HGB (Hemoglobin) [NCBI Gene 100323610], CEACAM5 (CEA cell adhesion molecule 5) [NCBI Gene 1048] {aka CD66e, CEA}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, NOD1 (nucleotide binding oligomerization domain containing 1) [NCBI Gene 10392] {aka CARD4, CLR7.1, NLRC1, hNod1}, GZMB (granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated serine esterase 1)) [NCBI Gene 100233184], CD2 (CD2 molecule) [NCBI Gene 914] {aka LFA-2, SRBC, T11}, HSPA4 (heat shock protein family A (Hsp70) member 4) [NCBI Gene 3308] {aka APG-2, HEL-S-5a, HS24/P52, HSPH2, RY, hsp70}, CD9 (CD9 molecule) [NCBI Gene 928] {aka BTCC-1, DRAP-27, MIC3, MRP-1, TSPAN-29, TSPAN29}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, LOC100524016 (mesothelin) [NCBI Gene 100524016] {aka MSLN}, ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}, MOG (myelin oligodendrocyte glycoprotein) [NCBI Gene 4340] {aka BTN6, BTNL11, MOGIG2, NRCLP7}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, IRF1 (interferon regulatory factor 1) [NCBI Gene 3659] {aka IMD117, IRF-1, MAR}, S (surface glycoprotein) [NCBI Gene 43740568] {aka spike glycoprotein}
- **Diseases:** T (MESH:D001260), acute lymphoblastic leukemia (MESH:D054198), COVID-19 (MESH:D000086382), ischemic heart diseases (MESH:D017202), infected (MESH:D007239), CVDs (MESH:D002318), AMI (MESH:D009203), Crohn's disease (MESH:D003424), cytotoxic (MESH:D064420), metastasis (MESH:D009362), RA (MESH:D001172), chronic infection (MESH:D000088562), sclerotic (MESH:C538213), Atherosclerosis (MESH:D050197), viral infection (MESH:D014777), colorectal cancer (MESH:D015179), synovial cell sarcoma (MESH:D013584), death (MESH:D003643), hypertension (MESH:D006973), demyelination (MESH:D003711), liver cancer (MESH:D006528), MS (MESH:D009103), joint destruction (MESH:D008105), fungal (MESH:D009181), HIV (MESH:D015658), febrile neutropenia (MESH:D064147), Infectious diseases (MESH:D003141), chronic diseases (MESH:D002908), glioblastoma (MESH:D005909), herpes (MESH:C536395), bladder cancer (MESH:D001749), breast cancer (MESH:D001943), EAE (MESH:D004681), inflammatory bowel disease (MESH:D015212), heart failure (MESH:D006333), B cell malignancies (MESH:D016393), infarct (MESH:D007238), Cytokine release (MESH:D000080424), cardiac (MESH:D006331), ovarian cancer (MESH:D010051), granulomas (MESH:D006099), adenocarcinomas (MESH:D000230), Multiple (MESH:D009104), Cancer (MESH:D009369), lupus nephritis (MESH:D008181), Sjogren's syndrome (MESH:D012859), neurological toxicities (MESH:D020258), lung cancer (MESH:D008175), graft-versus-host disease (MESH:D006086), HBV infection (MESH:D006509), prostate cancer (MESH:D011471), Cardiac fibrosis (MESH:D005355), melanoma (MESH:D008545), hyperlipidemia (MESH:D006949), headache (MESH:D006261), chronic inflammation (MESH:D007249), autoimmune and neurodegenerative disorder (MESH:D019636), injury (MESH:D014947), pancreatic duct adenocarcinoma (MESH:D010190), influenza (MESH:D007251)
- **Chemicals:** carbohydrate (MESH:D002241), S (MESH:D013455), BAH241 (-), MOF (MESH:C037042), hydrogen (MESH:D006859), PLGA (MESH:D000077182), beta-glucans (MESH:D047071), GW4869 (MESH:C468773), GXM (MESH:C027478), lipid (MESH:D008055), DC (MESH:D003841), PL-A (MESH:C033616), CR3022 (MESH:C000717587), PEG (MESH:D011092), glycan (MESH:D011134), adenosine (MESH:D000241), oxygen (MESH:D010100)
- **Species:** Homo sapiens (human, species) [taxon 9606], Aspergillus (genus) [taxon 5052], Mus musculus (house mouse, species) [taxon 10090], hepatitis C virus [taxon 11103], Hepatitis B virus (no rank) [taxon 10407], Human immunodeficiency virus 1 (no rank) [taxon 11676], Nicotiana tabacum (American tobacco, species) [taxon 4097], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049]
- **Cell lines:** CT26 — Mus musculus (Mouse), Mouse colon adenocarcinoma, Cancer cell line (CVCL_7254)

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12925206/full.md

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Source: https://tomesphere.com/paper/PMC12925206