# Polymer Nanoparticle-Based Photodynamic Therapy Combined with Immunotherapy for Solid Tumor Treatment

**Authors:** Jieling Lao, Qiuting Ye, Shijie Fan, Zhengqing Cheng, Pan Wu

PMC · DOI: 10.3390/cimb48030281 · 2026-03-05

## TL;DR

This paper reviews how polymer nanoparticles can be used in combination with immunotherapy to treat solid tumors by enhancing both local tumor destruction and immune system activation.

## Contribution

The paper provides a systematic review of recent advances in polymer nanoparticle design for photo-immunotherapy and their synergistic mechanisms with immunomodulatory agents.

## Key findings

- Polymer nanoparticles enhance local tumor ablation and activate systemic antitumor immune responses.
- Combining photodynamic therapy with immunomodulatory agents like TLR agonists and ICBs shows synergistic effects.
- Challenges in clinical translation and future directions for photo-immunotherapy are outlined.

## Abstract

Polymer nanoparticles have been widely studied for tumor treatment due to their excellent biocompatibility, structural diversity, and multi-functionality. Among their various applications, combining polymer-based photosensitizers with photodynamic therapy (PDT) and immunotherapy has emerged as a promising strategy for treating solid tumors. This combination not only enhances local tumor ablation but also activates systemic antitumor immune responses. Polymer Nanoparticles, with their unique photodynamic properties and ability to integrate multiple therapeutic modalities, offer a powerful platform for photo-immunotherapy. This review systematically discusses recent advances in the design of polymer Nanoparticles and their synergistic mechanisms when combined with immunomodulatory agents such as Toll-like receptor (TLR) agonists, STING agonists, and immune checkpoint inhibitors (ICBs). Moreover, we highlight challenges faced in clinical translation and outline future perspectives for the development of these combination therapies.

## Full-text entities

- **Genes:** Sting1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 72512] {aka 2610307O08Rik, ERIS, MPYS, Mita, STING, STING-beta}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Cd247 (CD247 antigen) [NCBI Gene 12503] {aka 4930549J05Rik, A430104F18Rik, Cd3, Cd3-eta, Cd3-zeta, Cd3h}, Cgas (cyclic GMP-AMP synthase) [NCBI Gene 214763] {aka E330016A19Rik, Mb21d1}, TLR10 (toll like receptor 10) [NCBI Gene 81793] {aka CD290}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 397286], Calr (calreticulin) [NCBI Gene 12317] {aka CRT, Calregulin}, TLR1 (toll like receptor 1) [NCBI Gene 7096] {aka CD281, TIL, TIL. LPRS5, rsc786}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Adgre1 (adhesion G protein-coupled receptor E1) [NCBI Gene 13733] {aka DD7A5-7, EGF-TM7, Emr1, F4/80, Gpf480, Ly71}, Tlr9 (toll-like receptor 9) [NCBI Gene 81897], CD274 (CD274 molecule) [NCBI Gene 574058] {aka PDL1}, Mrc1 (mannose receptor, C type 1) [NCBI Gene 17533] {aka CD206, MR}, Tbk1 (TANK-binding kinase 1) [NCBI Gene 56480] {aka 1200008B05Rik}, CD80 (CD80 molecule) [NCBI Gene 397161] {aka B7-1}, Cd86 (CD86 antigen) [NCBI Gene 12524] {aka B7, B7-2, B7.2, B70, CLS1, Cd28l2}, CD86 (CD86 molecule) [NCBI Gene 397441], Hmgb1 (high mobility group box 1) [NCBI Gene 15289] {aka HMG-1, Hmg1, SBP-1, p30}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, Ifnb1 (interferon beta 1, fibroblast) [NCBI Gene 15977] {aka IFN-beta, IFNB, If1da1, Ifb}, STING1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 340061] {aka ERIS, MITA, MPYS, NET23, SAVI, STING}, CD28 [NCBI Gene 100738615], Irf3 (interferon regulatory factor 3) [NCBI Gene 54131] {aka C920001K05Rik, IRF-3}
- **Diseases:** breast cancer (MESH:D001943), hypoxic (MESH:D002534), AIE (MESH:D014012), inflammatory (MESH:D007249), HNSCC (MESH:D000077195), Solid Tumors (MESH:D009369), hypoxia (MESH:D000860), gastric cancer (MESH:D013274), toxicity (MESH:D064420), phototoxicity (MESH:D017484), injury to (MESH:D014947), ISC (MESH:C537866)
- **Chemicals:** saccharides (MESH:D002241), metal (MESH:D008670), ATP (MESH:D000255), porphyrin (MESH:D011166), TBT (MESH:C027647), benzothiadiazole (MESH:C015700), glycol (MESH:D006018), pembrolizumab (MESH:C582435), polythiophene (MESH:C066730), water (MESH:D014867), carbazole (MESH:C041514), CpG (MESH:C015772), naphthalimide (MESH:D053644), folic acid (MESH:D005492), ROS (MESH:D017382), singlet oxygen (MESH:D026082), NBS (MESH:D009556), CGAMP (MESH:C584311), glutathione (MESH:D005978), glycolic acids (MESH:C031149), diimide (MESH:C038867), OH (MESH:C031356), methylene blue (MESH:D008751), thiazine (MESH:D013843), TPE (MESH:C000617116), BODIPY (MESH:C095489), PLGA (MESH:D000077182), PEI (MESH:D011094), polyesters (MESH:D011091), RGD (MESH:C047981), IMQ (MESH:D000077271), Verteporfin (MESH:D000077362), Ir (MESH:D007495), nivolumab (MESH:D000077594), CpG oligodeoxynucleotides (MESH:C408982), morpholine (MESH:C037574), Polymer (MESH:D011108), DeltaE_ST (-), PNBS (MESH:C081297), Nile blue (MESH:C008619), H (MESH:D006859), PLA (MESH:C033616), disulfide (MESH:D004220), superoxide (MESH:D013481), oxygen (MESH:D010100), C (MESH:D002244)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), 4T1 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_0125)

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13025029/full.md

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Source: https://tomesphere.com/paper/PMC13025029