# Cell membranes-encapsulated gadolinium-doped carbon dots for the efficient photothermal and immunotherapeutic synergistic treatment of hepatocellular carcinoma

**Authors:** Wenhui Dong, Yingying Wei, Chenyue Cao, Hongkai Mu, Shizhao Zhou, Yueyong Xiao, Yongzhen Yang, Lin Chen, Shiping Yu

PMC · DOI: 10.1186/s12951-026-04123-9 · Journal of Nanobiotechnology · 2026-02-21

## TL;DR

This paper introduces a new nanoplatform for treating liver cancer by combining targeted cell membrane encapsulation with photothermal therapy and immune activation.

## Contribution

The novel contribution is a biomimetic nanosystem using Gd-doped carbon dots and HCC cell membranes for combined photothermal and immunotherapy.

## Key findings

- The Gd-CDs@HCM system achieved an 84.9% primary tumor ablation rate.
- The system induces immunogenic cell death and enhances systemic anti-tumor immunity.
- Bimodal imaging allows real-time monitoring of the treatment process.

## Abstract

Hepatocellular carcinoma (HCC), a predominant subtype of liver cancer, is witnessing a rising global incidence and urgently demands the development of innovative nanoplatforms that integrate precise therapeutic and immune regulatory functions. To address the limitations of conventional monotherapies, which often suffer from inadequate tumor targeting, insufficient efficacy, and limited immune activation, this study employs a "biomimetic targeting-synergy therapy" approach. We have engineered a composite system consisting of gadolinium-doped carbon dots (Gd-CDs) enveloped with hepatocellular carcinoma cell membranes (HCM), thereby imparting homologous targeting capabilities and immune activation properties. This Gd-CDs@HCM system facilitates photothermal immunotherapy, guided by bimodal fluorescence (FL) and magnetic resonance (MR) imaging. Upon laser irradiation, Gd-CDs@HCM can induce immunogenic cell death (ICD) in tumor cells. The tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs) released during ICD collaboratively enhance systemic anti-tumor immunity in conjunction with HCM, achieving a primary tumor ablation rate of 84.9% and inhibiting tumor progression. Consequently, this research offers an innovative strategy for real-time monitoring and precise synergistic treatment of HCC by utilizing FL/MR bimodal imaging and integrating bionic targeting, localized thermal ablation, and immune activation functions.

The online version contains supplementary material available at 10.1186/s12951-026-04123-9.

## Linked entities

- **Chemicals:** gadolinium (PubChem CID 23982)
- **Diseases:** hepatocellular carcinoma (MONDO:0007256)

## Full-text entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, ANXA5 (annexin A5) [NCBI Gene 308] {aka ANX5, CPB-I, ENX2, HEL-S-7, PP4, RPRGL3}, Cd80 (CD80 antigen) [NCBI Gene 12519] {aka B71, Cd28l, Ly-53, Ly53, MIC17, TSA1}, IRF1 (interferon regulatory factor 1) [NCBI Gene 3659] {aka IMD117, IRF-1, MAR}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Il2ra (interleukin 2 receptor, alpha chain) [NCBI Gene 16184] {aka CD25, Il2r, Ly-43}, ANGPTL3 (angiopoietin like 3) [NCBI Gene 27329] {aka ANG-5, ANGPT5, ANL3, FHBL2}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Calr (calreticulin) [NCBI Gene 12317] {aka CRT, Calregulin}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, Cd86 (CD86 antigen) [NCBI Gene 12524] {aka B7, B7-2, B7.2, B70, CLS1, Cd28l2}, HSPA4 (heat shock protein family A (Hsp70) member 4) [NCBI Gene 3308] {aka APG-2, HEL-S-5a, HS24/P52, HSPH2, RY, hsp70}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, Itgax (integrin alpha X) [NCBI Gene 16411] {aka Cd11c, Cr4, N418}, Apc (APC, WNT signaling pathway regulator) [NCBI Gene 11789] {aka CC1, Min, mAPC}, CXCL16 (C-X-C motif chemokine ligand 16) [NCBI Gene 58191] {aka CXCLG16, SR-PSOX, SRPSOX}, Foxp3 (forkhead box P3) [NCBI Gene 20371] {aka JM2, scurfin, sf}, Gpt (glutamic pyruvic transaminase, soluble) [NCBI Gene 76282] {aka 1300007J06Rik, 2310022B03Rik, ALT, ALT1, Gpt-1, Gpt1}, HMGB1 (high mobility group box 1) [NCBI Gene 3146] {aka HMG-1, HMG1, HMG3, SBP-1}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, Slc17a5 (solute carrier family 17 (anion/sugar transporter), member 5) [NCBI Gene 235504] {aka 4631416G20Rik, 4732491M05, AST, ISSD, NSD, SD}, IL7R (interleukin 7 receptor) [NCBI Gene 3575] {aka CD127, CDW127, IL-7R-alpha, IL-7Ralpha, IL7RA, IL7Ralpha}, CALR (calreticulin) [NCBI Gene 811] {aka CALR1, CRT, HEL-S-99n, RO, SSA, cC1qR}, Hmgb1 (high mobility group box 1) [NCBI Gene 15289] {aka HMG-1, Hmg1, SBP-1, p30}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, Cd247 (CD247 antigen) [NCBI Gene 12503] {aka 4930549J05Rik, A430104F18Rik, Cd3, Cd3-eta, Cd3-zeta, Cd3h}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345] {aka D630048A14Rik, Ki-67, Ki67}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}
- **Diseases:** hyperthermia (MESH:D005334), damage (MESH:D020263), Hemolysis (MESH:D006461), inflammatory (MESH:D007249), metabolic disturbances (MESH:D024821), fibrosis (MESH:D005355), Cancer (MESH:D009369), HCC (MESH:D006528), necrosis (MESH:D009336), liver tumor (MESH:D008113), TAAs (MESH:C535887), ICD (MESH:D003643), Cytotoxicity (MESH:D064420), subcutaneous (MESH:D013352)
- **Chemicals:** water (MESH:D014867), xenon (MESH:D014978), SDS (MESH:D012967), -SO3- (MESH:C011118), paraffin (MESH:D010232), Calcein AM (MESH:C085925), Saline (MESH:D012965), TX-100 (MESH:C551282), Gd3+ (MESH:C026226), O (MESH:D010100), N (MESH:D009584), PEG (MESH:D011092), Coomassie Brilliant Blue (MESH:C004692), gadodiamide (MESH:C064925), Triton X-100 (MESH:D017830), polyacrylamide (MESH:C016679), streptomycin (MESH:D013307), C (MESH:D002244), Gd (MESH:D005682), ATP (MESH:D000255), BCA (MESH:C047117), CO2 (MESH:D002245), CA (MESH:D019343), paraformaldehyde (MESH:C003043), sulfonate (MESH:D000476), agarose (MESH:D012685), eosin (MESH:D004801), H (MESH:D006859), DTPA (MESH:D004369), DAPI (MESH:C007293), PI (MESH:D011419), graphite (MESH:D006108), Gd-CDs (-), ozone (MESH:D010126), H&amp;E (MESH:D006371), crystal violet (MESH:D005840), S (MESH:D013455), Gd-DTPA (MESH:D019786), hematoxylin (MESH:D006416), penicillin (MESH:D010406), PMSF (MESH:D010664), ICG (MESH:D007208)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** THLE-2 — Homo sapiens (Human), Transformed cell line (CVCL_3803), CCK-8 — Homo sapiens (Human), T-cell prolymphocytic leukemia, Cancer cell line (CVCL_5443), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), C57BL/6 J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW), Hepa1-6 — Mus musculus (Mouse), Hepatocellular carcinoma of the mouse, Cancer cell line (CVCL_0327), BALB/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184)

## Full text

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## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12967015/full.md

## References

1 references — full list in the complete paper: https://tomesphere.com/paper/PMC12967015/full.md

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Source: https://tomesphere.com/paper/PMC12967015