# Quercetin and Its Nano‐Based Formulations Against Skin Cancer: A Narrative Review

**Authors:** Mahtab Khanyabzadeh, Alireza Emamifar, Nikoo Emtiazi, Amir Nazari, Masoumeh Shekarriz, Amin Karami, Fateme Hashem Beik Mahallati, Rahineh Nomani Lafmejani, Atieh Dariush, Seyed Mohammad Mahdi Rohani, Elaheh Mohseni Vadeghani, Negin Khoshnood, Hamid Reza Ojaghi, Fatemeh Rezaei‐Tazangi, Reza Arefnezhad

PMC · DOI: 10.1002/hsr2.71920 · Health Science Reports · 2026-02-28

## TL;DR

This review explores how quercetin, a natural compound, and its nano-based formulations may offer new treatment options for skin cancer by improving its effectiveness and delivery.

## Contribution

The novelty lies in integrating natural compound therapy with nanotechnology to address limitations in skin cancer treatment.

## Key findings

- Quercetin modulates pathways like apoptosis and DNA repair to inhibit skin cancer cell growth.
- Nano-based delivery systems enhance quercetin's stability, permeability, and bioavailability.
- Preclinical studies show improved therapeutic effects with nano-formulated quercetin.

## Abstract

Skin cancer is one of the most prevalent malignancies worldwide, characterized by the abnormal growth of skin cells and significant clinical challenges. Conventional treatments—including surgery, chemotherapy, and radiotherapy—often suffer from limitations such as adverse side effects, tumor resistance, and inadequate efficacy. In this context, natural compounds have garnered attention as alternative therapeutic agents. Quercetin, a flavonoid widely distributed in fruits and vegetables, is recognized for its anti‐cancer, anti‐inflammatory, and antioxidant properties. However, its clinical application is hindered by poor solubility, low bioavailability, and limited skin permeation. Recent advances in nanotechnology have led to the development of nano‐based formulations that can enhance the pharmacological performance of quercetin, offering promising avenues for skin cancer management.

This review aims to provide a comprehensive analysis of skin cancer pathogenesis and to evaluate the mechanistic insights and therapeutic potential of quercetin—alone and in nano‐formulated systems—in preclinical models. The novelty of this review lies in its integrated approach, combining an overview of natural compound therapy with the latest cutting‐edge nanotechnology strategies to overcome current treatment challenges.

This literature review was performed by searching related words, including “Skin cancer,” “Melanoma,” “Basal cell carcinoma,” “Squamous cell carcinoma,” “Quercetin,” “Nanotechnology,” in different databases like Google Scholar, Scopus, PubMed, Web of Science, and Scientific Information Databases until 2025.

Preclinical studies indicate that quercetin modulates multiple cellular and molecular pathways—such as those regulating apoptosis, cell cycle progression, mitochondrial function, and DNA repair—to inhibit proliferation, migration, and invasion of skin cancer cells. Nano‐based delivery systems (e.g., titanium dioxide nanoparticles, nanogels, and lipid carrier gels) have been shown to further enhance these therapeutic effects by improving quercetin's stability, skin permeability, and bioavailability.

Integrating quercetin with nano‐based formulations presents a novel and promising approach for targeted skin cancer therapy. While preclinical results are encouraging, further experimental and clinical investigations are necessary to fully validate these findings and facilitate translation into clinical practice.

## Linked entities

- **Chemicals:** Quercetin (PubChem CID 5280343)
- **Diseases:** Skin cancer (MONDO:0002898), Melanoma (MONDO:0005105), Basal cell carcinoma (MONDO:0005341), Squamous cell carcinoma (MONDO:0005096)

## Full-text entities

- **Genes:** XPA (XPA, DNA damage recognition and repair factor) [NCBI Gene 7507] {aka XP1, XPAC}, NOTCH1 (notch receptor 1) [NCBI Gene 4851] {aka AOS5, AOVD1, TAN1, hN1}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, Tet1 (tet methylcytosine dioxygenase 1) [NCBI Gene 52463] {aka 2510010B09Rik, Cxxc6, D10Ertd17e, LCX, mKIAA1676}, alp (alopecia, recessive) [NCBI Gene 11691], SHH (sonic hedgehog signaling molecule) [NCBI Gene 6469] {aka HHG1, HLP3, HPE3, MCOPCB5, SMMCI, ShhNC}, MC1R (melanocortin 1 receptor) [NCBI Gene 4157] {aka CMM5, MSH-R, SHEP2}, BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673] {aka B-RAF1, B-raf, BRAF-1, BRAF1, NS7, RAFB1}, CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, Mmp9 (matrix metallopeptidase 9) [NCBI Gene 17395] {aka B/MMP9, Clg4b, Gel B, MMP-9, pro-MMP-9}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, Fos (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 14281] {aka D12Rfj1, c-fos, cFos}, MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609] {aka JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, Anxa5 (annexin A5) [NCBI Gene 11747] {aka Anx5, CPB-I}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, IL5 (interleukin 5) [NCBI Gene 3567] {aka EDF, IL-5, TRF}, Mmp2 (matrix metallopeptidase 2) [NCBI Gene 17390] {aka Clg4a, GelA, MMP-2}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, NRAS (NRAS proto-oncogene, GTPase) [NCBI Gene 4893] {aka ALPS4, CMNS, N-ras, NCMS, NRAS1, NS6}, ZHX2 (zinc fingers and homeoboxes 2) [NCBI Gene 22882] {aka AFR1, RAF}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, PPP6C (protein phosphatase 6 catalytic subunit) [NCBI Gene 5537] {aka PP6, PP6C}, Igf1r (insulin-like growth factor I receptor) [NCBI Gene 16001] {aka A330103N21Rik, CD221, D930020L01, IGF-1R, hyft}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, SMO (smoothened, frizzled class receptor) [NCBI Gene 6608] {aka CRJS, FZD11, Gx, PHLS, SMOH}, Hif1a (hypoxia inducible factor 1, alpha subunit) [NCBI Gene 15251] {aka HIF-1-alpha, HIF1-alpha, HIF1alpha, MOP1, bHLHe78}, Sdsl (serine dehydratase-like) [NCBI Gene 257635] {aka 4432411H13Rik, SDH1, SDS-RS1, TDH}, Pim1 (Pim1, proto-oncogene, serine/threonine kinase) [NCBI Gene 18712] {aka Pim-1}, SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696] {aka BNSP, BSPI, ETA-1, OPN}, EPHB2 (EPH receptor B2) [NCBI Gene 2048] {aka BDPLT22, CAPB, DRT, EK5, EPHT3, ERK}, Mir17 (microRNA 17) [NCBI Gene 723905] {aka Mirn17, mir-17, mmu-mir-17}, Alb (albumin) [NCBI Gene 11657] {aka Alb-1, Alb1, BCL001, BCL002, BPL001}, Slc5a1 (solute carrier family 5 (sodium/glucose cotransporter), member 1) [NCBI Gene 20537] {aka Sglt1}, Rigi (RNA sensor RIG-I) [NCBI Gene 230073] {aka 6430573D20Rik, C330021E21, Ddx58, RIG-I, RLR-1}, Stat1 (signal transducer and activator of transcription 1) [NCBI Gene 20846] {aka 2010005J02Rik}, Rps6kb1 (ribosomal protein S6 kinase B1) [NCBI Gene 72508] {aka 2610318I15Rik, P70S6K1, S6K, S6K-beta-1, S6K1, p70 S6K-alpha}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, Igf1 (insulin-like growth factor 1) [NCBI Gene 16000] {aka C730016P09Rik, Igf-1, Igf-I}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, ERCC2 (ERCC excision repair 2, TFIIH core complex helicase subunit) [NCBI Gene 2068] {aka COFS2, CXPD, EM9, TFIIH, TTD, TTD1}, LATS1 (large tumor suppressor kinase 1) [NCBI Gene 9113] {aka WARTS, wts}, GLI1 (GLI family zinc finger 1) [NCBI Gene 2735] {aka GLI, PAPA8, PPD1}, Axl (AXL receptor tyrosine kinase) [NCBI Gene 26362] {aka Ark, Tyro7, Ufo}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, PTCH1 (patched 1) [NCBI Gene 5727] {aka BCNS, BCNS1, NBCCS, PTC, PTC1, PTCH}
- **Diseases:** Squamous cell carcinoma (MESH:D002294), damage (MESH:D020263), non-small cell lung cancer (MESH:D002289), hemolytic (MESH:D006461), skin hyperplasia (MESH:D006965), Basal cell carcinoma (MESH:D002280), hepatic or renal toxicities (MESH:D056486), uveal melanoma (MESH:C536494), dermatitis (MESH:D003872), catalepsy (MESH:D002375), tingling (MESH:D010292), stomach discomfort (MESH:D013272), heart failure (MESH:D006333), breast cancer (MESH:D001943), Skin cancer (MESH:D012878), papilloma (MESH:D010212), head and neck SCC (MESH:D006258), Cytotoxicity (MESH:D064420), organ toxicity (MESH:D019965), cardiovascular diseases (MESH:D002318), diabetes (MESH:D003920), blood malignancy (MESH:D009369), hypertensive (MESH:D006973), hyperplastic polyps of the cecum (MESH:D002430), carcinogenic (MESH:D011230), colorectal cancer (MESH:D015179), pancreatic cancer (MESH:D010190), skin damage (MESH:D012871), neurodegenerative impairments (MESH:D019636), headache (MESH:D006261), inflammation (MESH:D007249), prostate cancer (MESH:D011471), Melanoma (MESH:D008545)
- **Chemicals:** glucose (MESH:D005947), 3-hydroxyflavones (MESH:C041477), sulindac (MESH:D013467), ethanol (MESH:D000431), EE (MESH:D004997), flavonoid (MESH:D005419), fexofenadine (MESH:C093230), NO (MESH:D009569), Cremophor RH40 (MESH:C022131), cyclobutane (MESH:D003503), heavy metals (MESH:D019216), glycosides (MESH:D006027), valsartan (MESH:D000068756), ROS (MESH:D017382), PLGA (MESH:D000077182), silver (MESH:D012834), resveratrol (MESH:D000077185), aglycone (MESH:C458179), arsenic (MESH:D001151), alpha-methyl-p-tyrosine (MESH:D019805), calcium oxalate (MESH:D002129), DMBA (MESH:C082386), imatinib (MESH:D000068877), Lipid (MESH:D008055), digoxin (MESH:D004077), perphenazine (MESH:D010546), melanin (MESH:D008543), Carbopol 940 (MESH:C006903), ranolazine (MESH:D000069458), 5-methylcytosine (MESH:D044503), 7, 12-dimethyl Benz (a) anthracene (MESH:D015127), rutinose (MESH:C539209), zinc oxide (MESH:D015034), polyphenol (MESH:D059808), water (MESH:D014867), palladium (MESH:D010165), erlotinib (MESH:D000069347), GSH (MESH:D005978), TiO2 (MESH:C009495), peroxynitrite (MESH:D030421), cerium oxide (MESH:C030583), etoposide (MESH:D005047), carbon (MESH:D002244), PS (MESH:D010718), vemurafenib (MESH:D000077484), quercetin glycoside (MESH:D012431), pravastatin (MESH:D017035), polymers (MESH:D011108), oil (MESH:D009821), U0126 (MESH:C113580), lactic acid (MESH:D019344), bilirubin (MESH:D001663), tamoxifen (MESH:D013629), dasatinib (MESH:D000069439), carbon nanotubes (MESH:D037742), paclitaxel (MESH:D017239), isoquercetin (MESH:C016527), temozolomide (MESH:D000077204), C15H10O7 (MESH:D011794), MTT (MESH:C070243)
- **Species:** Allium sativum (garlic, species) [taxon 4682], Allium cepa (onion, species) [taxon 4679], Bos taurus (bovine, species) [taxon 9913], Curcuma longa (turmeric, species) [taxon 136217], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Malus domestica (apple, species) [taxon 3750]
- **Mutations:** C-7 of the A, serine/threonine, C-3 of the C, A375
- **Cell lines:** MT1/2 — Homo sapiens (Human), Transformed cell line (CVCL_2631), B16 — Mus musculus (Mouse), Hybridoma (CVCL_U043), B16-F10 — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_0159), SKMEL-28 — Homo sapiens (Human), Cutaneous melanoma, Cancer cell line (CVCL_0526), OCM-1 — Homo sapiens (Human), Amelanotic melanoma, Cancer cell line (CVCL_6935), Hacat cell — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0038), A431 — Homo sapiens (Human), Skin squamous cell carcinoma, Cancer cell line (CVCL_0037), SK-MEL-1 — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_0068), B16-F1O — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_0158), SKMEL-103 — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_6069)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12949835/full.md

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12949835/full.md

## References

193 references — full list in the complete paper: https://tomesphere.com/paper/PMC12949835/full.md

---
Source: https://tomesphere.com/paper/PMC12949835