# Next-Generation Hydrogels Integrating Natural Antioxidants and Microbiome Modulators for Improved Cancer Management

**Authors:** Camelia Munteanu, Eftimia Prifti, Larisa Achim, Ciprian Nicolae Silaghi, Sorin Marian Mârza

PMC · DOI: 10.3390/gels12030249 · Gels · 2026-03-16

## TL;DR

This review explores new hydrogels that combine natural antioxidants and microbiome modulators to improve cancer treatment by addressing issues like low bioavailability and targeted delivery.

## Contribution

The paper introduces next-generation hydrogels as a novel platform for delivering natural antioxidants and microbiome modulators in cancer therapy.

## Key findings

- Natural antioxidants and microbiome modulators show therapeutic potential in cancer treatment.
- Hydrogels can protect and deliver these agents in a site-specific and controlled manner.
- Current challenges include bioavailability and stability, which hydrogels aim to overcome.

## Abstract

Cancer remains a leading cause of death worldwide, and current treatments are often limited by toxicity and resistance. Emerging research highlights the crucial roles played by gut microbiome dysbiosis and oxidative stress in cancer development and treatment response. Through their antioxidant, anti-inflammatory, and immunomodulatory properties, natural antioxidants such as resveratrol, along with microbiome modulators like probiotics, prebiotics, and synbiotics, offer promising therapeutic benefits. However, issues such as low bioavailability, instability, and challenges related to targeted delivery hinder the clinical translation of these bioactive compounds. Next-generation hydrogels have emerged as adaptable platforms capable of delivering and protecting these agents in a site-specific and controlled manner. This review summarizes the design and synthesis of multifunctional hydrogels incorporating natural antioxidants and microbiome modulators for cancer therapy.

## Linked entities

- **Chemicals:** resveratrol (PubChem CID 5056)
- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, SYK (spleen associated tyrosine kinase) [NCBI Gene 6850] {aka IMD82, p72-Syk}, NFKBIA (NFKB inhibitor alpha) [NCBI Gene 4792] {aka EDAID2, IKBA, MAD-3, NFKBI}, HDAC9 (histone deacetylase 9) [NCBI Gene 9734] {aka HD7, HD7b, HD9, HDAC, HDAC7B, HDAC9B}, PRKAA2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 5563] {aka AMPK, AMPK2, AMPKa2, PRKAA}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TLR2 (toll like receptor 2) [NCBI Gene 7097] {aka CD282, TIL4}, PGP (phosphoglycolate phosphatase) [NCBI Gene 283871] {aka AUM, G3PP, PGPase}, CDKN1B (cyclin dependent kinase inhibitor 1B) [NCBI Gene 1027] {aka CDKN4, KIP1, MEN1B, MEN4, P27KIP1}, CDK4 (cyclin dependent kinase 4) [NCBI Gene 1019] {aka CMM3, MCPH31, PSK-J3}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, CCND1 (cyclin D1) [NCBI Gene 595] {aka BCL1, D11S287E, PRAD1, U21B31}, CDK6 (cyclin dependent kinase 6) [NCBI Gene 1021] {aka MCPH12, PLSTIRE}, CDKN1A (cyclin dependent kinase inhibitor 1A) [NCBI Gene 1026] {aka CAP20, CDKN1, CIP1, MDA-6, P21, SDI1}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, SCARB1 (scavenger receptor class B member 1) [NCBI Gene 949] {aka CD36L1, CLA-1, CLA1, HDLCQ6, HDLQTL6, SR-BI}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, ABCB1 (ATP binding cassette subfamily B member 1) [NCBI Gene 5243] {aka ABC20, CD243, CLCS, ENPAT, GP170, MDR1}, CLEC7A (C-type lectin domain containing 7A) [NCBI Gene 64581] {aka BGR, CANDF4, CD369, CLECSF12, DECTIN1, SCARE2}, Eln (elastin) [NCBI Gene 13717] {aka E030024M20Rik}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, GJA1 (gap junction protein alpha 1) [NCBI Gene 2697] {aka AVSD3, CMDR, CX43, EKVP, EKVP3, GJAL}
- **Diseases:** pancreatic cancer (MESH:D010190), diabetes (MESH:D003920), gastrointestinal toxicity (MESH:D005767), CRC (MESH:D015179), esophageal cancer (MESH:D004938), bladder cancer (MESH:D001749), tumorigenic (MESH:D002471), toxicity (MESH:D064420), immune dysfunction (MESH:D007154), cardiovascular disease (MESH:D002318), pain (MESH:D010146), dysbiosis (MESH:D064806), carcinogenesis (MESH:D063646), death (MESH:D003643), corneal disease (MESH:D003316), fungal infection (MESH:D009181), metastasis (MESH:D009362), bacteremia (MESH:D016470), injury to (MESH:D014947), septic shock (MESH:D012772), infected (MESH:D007239), postoperative (MESH:D019106), inflammatory bowel disease (MESH:D015212), Chronic inflammation (MESH:D007249), carcinogenic (MESH:D011230), fatigue (MESH:D005221), hyperthermia (MESH:D005334), breast cancer (MESH:D001943), Immune dysregulation (OMIM:614878), fibrosis (MESH:D005355), Cancer (MESH:D009369), chronic (MESH:D002908), bacterial translocation (MESH:D014178), nerve disease (MESH:D009901), cartilage defects (MESH:D002357)
- **Chemicals:** pyrogallol (MESH:D011748), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid (MESH:C002502), lipid (MESH:D008055), Polysaccharide (MESH:D011134), PAA (MESH:C006903), gold (MESH:D006046), fructooligosaccharides (MESH:C116580), HA (MESH:D006820), carotenoid (MESH:D002338), ketones (MESH:D007659), silver (MESH:D012834), inulin (MESH:D007444), capecitabine (MESH:D000069287), 5-fluorouracil (MESH:D005472), pectin (MESH:D010368), PLGA (MESH:D000077182), Prebiotics (MESH:D056692), Catechins (MESH:D002392), beta-carotene (MESH:D019207), polyene (MESH:D011090), Chitosan (MESH:D048271), xylan (MESH:D014990), RSV (MESH:D000077185), iron oxide (MESH:C000499), alkali (MESH:D000468), Pluronic F127 (MESH:D020442), superoxide (MESH:D013481), disulfide (MESH:D004220), Paclitaxel (MESH:D017239), carbon (MESH:D002244), carboxymethyl cellulose (MESH:D002266), PVA (MESH:D011142), Oxygen (MESH:D010100), Carotenoid Lycopene (-), gallic acid (MESH:D005707), polymer (MESH:D011108), cerium oxide (MESH:C030583), NO (MESH:D009569), hydrogen (MESH:D006859), curcumin (MESH:D003474), calcium (MESH:D002118), MXene (MESH:C000723374), Lignin (MESH:D008031), streptozotocin (MESH:D013311), EGC (MESH:C057580), carbodi-imide (MESH:D002234), Butyrate (MESH:D002087), D-glucose (MESH:D005947), pembrolizumab (MESH:C582435), beta-Glucans (MESH:D047071), PAAm (MESH:C016679), rituximab (MESH:D000069283), water (MESH:D014867), silica (MESH:D012822), Bupivacaine (MESH:D002045), SCFAs (MESH:D005232), EGCG (MESH:C045651), polyphenol (MESH:D059808), GO (MESH:C000628730), catechol (MESH:C034221)
- **Species:** Wolfiporia cocos (species) [taxon 81056], Bifidobacterium animalis subsp. lactis (subspecies) [taxon 302911], Clostridioides difficile (species) [taxon 1496], Homo sapiens (human, species) [taxon 9606], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], gut metagenome (species) [taxon 749906], Mus musculus (house mouse, species) [taxon 10090], Rodentia (rodent, order) [taxon 9989], Camellia sinensis (black tea, species) [taxon 4442], Solanum lycopersicum (tomato, species) [taxon 4081], Escherichia coli (E. coli, species) [taxon 562], Lacticaseibacillus casei (species) [taxon 1582], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Rattus norvegicus (brown rat, species) [taxon 10116], Fusobacterium nucleatum (species) [taxon 851]
- **Cell lines:** MIA PaCa-2 — Homo sapiens (Human), Pancreatic undifferentiated carcinoma, Cancer cell line (CVCL_0428), HCT15 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0292), H358 — Homo sapiens (Human), Minimally invasive lung adenocarcinoma, Cancer cell line (CVCL_1559), Panc-1 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0480), L929 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_AR58), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), SW480 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0546)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13025991/full.md

## References

284 references — full list in the complete paper: https://tomesphere.com/paper/PMC13025991/full.md

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Source: https://tomesphere.com/paper/PMC13025991