# Development of niosomal nanoparticles loaded with cisplatin and vorinostat combination for cancer therapy

**Authors:** Hazar Ali, Zainab Lafi, Naeem Shalan

PMC · DOI: 10.1371/journal.pone.0342344 · PLOS One · 2026-02-06

## TL;DR

Researchers developed niosomal nanoparticles to deliver cisplatin and vorinostat together, improving cancer treatment by enhancing drug efficacy and reducing toxicity.

## Contribution

A novel niosomal nanoparticle system for co-delivering cisplatin and vorinostat with improved physicochemical and anticancer properties.

## Key findings

- Niosomal nanoparticles achieved high encapsulation efficiency (89.3% for cisplatin and 52.1% for vorinostat) and sustained drug release over 72 hours.
- The co-loaded nanoparticles showed significantly reduced IC50 values in multiple cancer cell lines compared to free drugs, indicating enhanced cytotoxicity.
- The formulation induced increased apoptosis and reduced colony formation, demonstrating synergistic anticancer effects.

## Abstract

Cisplatin (CIS) remains a cornerstone of chemotherapy but is limited by resistance and systemic toxicity. Combining DNA-damaging agents with epigenetic modulators such as vorinostat (VOR) offers a promising strategy to enhance efficacy. However, the co-delivery of these drugs is challenging due to their distinct physicochemical properties. The aim was to develop and characterize niosomal nanoparticles co-loaded with CIS and VOR (NIO-CIS-VOR) and to assess their physicochemical characteristics and in vitro anticancer activity. Niosomes were prepared using ethanol injection, with CIS entrapped in the aqueous core and VOR in the lipid bilayer. Characterization included particle size, polydispersity index (PDI), and zeta potential by DLS, morphology by TEM, and encapsulation confirmation by FTIR. Encapsulation efficiency (EE%) and drug release were determined by HPLC. Cytotoxicity, caspase-3/7 activation, colony formation, and wound healing assays were conducted in HT-29, A549, and PANC-1 cancer cell lines. Optimized NIO-CIS-VOR nanoparticles exhibited a mean diameter of 152.7 nm, PDI of 0.12, and zeta potential of –9.79 mV, with spherical morphology. Encapsulation efficiency of NIO-CIS-VOR reached 89.3% for CIS and 52.1% for VOR. The formulation showed sustained release over 72 h, with cumulative release of 62% (CIS) and 38% (VOR) at 6 h. Cytotoxicity assays demonstrated markedly reduced IC50 values for NIO-CIS-VOR compared with free drugs: 1.8 µM vs. 4.47 µM (CIS) and 3.4 µM (VOR) in HT-29; 0.95 µM vs. 3.8 µM and 3.1 µM in A549; and 2.37 µM vs. 13.9 µM and 3.66 µM in PANC-1. Enhanced apoptosis and reduced colony formation further confirmed superior anticancer activity.In Conclusion the Co-loaded niosomes achieved efficient co-delivery, sustained release, and synergistic anticancer effects, highlighting NIO-CIS-VOR as a promising nanocarrier for combination cancer therapy.

## Linked entities

- **Chemicals:** cisplatin (PubChem CID 5460033), vorinostat (PubChem CID 5311)
- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** HDAC9 (histone deacetylase 9) [NCBI Gene 9734] {aka HD7, HD7b, HD9, HDAC, HDAC7B, HDAC9B}, CDKN1A (cyclin dependent kinase inhibitor 1A) [NCBI Gene 1026] {aka CAP20, CDKN1, CIP1, MDA-6, P21, SDI1}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, CISH (cytokine inducible SH2 containing protein) [NCBI Gene 1154] {aka BACTS2, CIS, CIS-1, G18, SOCS}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, ANXA5 (annexin A5) [NCBI Gene 308] {aka ANX5, CPB-I, ENX2, HEL-S-7, PP4, RPRGL3}, TUBA1B (tubulin alpha 1b) [NCBI Gene 10376] {aka K-ALPHA-1}, TYMS (thymidylate synthetase) [NCBI Gene 7298] {aka DKCD, HST422, TMS, TS}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}
- **Diseases:** Cancer (MESH:D009369), ovarian cancer (MESH:D010051), Lung Carcinoma (MESH:D008175), Ductal Adenocarcinoma (MESH:D000230), Cytotoxicity (MESH:D064420), Pancreatic Cancer (MESH:D010190), Colorectal Adenocarcinoma (MESH:D003110), colon (MESH:D003108), Non-small Cell Lung Cancer (MESH:D002289), colon cancer (MESH:D015179), triple-negative (MESH:D064726), breast cancer (MESH:D001943), lung (MESH:D008171), metastasis (MESH:D009362), pancreatic (MESH:D010195), prostate cancer (MESH:D011471)
- **Chemicals:** Phosphotungstic Acid (MESH:D010772), polyoxyethylene (MESH:D011092), DMEM (-), formazan (MESH:D005562), Doxorubicin (MESH:D004317), DDT (MESH:D003634), Capecitabine (MESH:D000069287), fatty acid (MESH:D005227), lipid (MESH:D008055), ether (MESH:D004986), hydroxamic acid (MESH:D006877), CIC (MESH:C037401), methanol (MESH:D000432), platinum (MESH:D010984), VOR (MESH:D000077337), Apigenin (MESH:D047310), BCA (MESH:C047117), amino acids (MESH:D000596), amides (MESH:D000577), MTT (MESH:C070243), Flavonoid (MESH:D005419), cholesterol (MESH:D002784), hydrogen (MESH:D006859), alcohol (MESH:D000438), hydroxyl (MESH:D017665), water (MESH:D014867), 5-FU (MESH:D005472), carbon (MESH:D002244), Tween (MESH:D011136), amine (MESH:D000588), DMSO (MESH:D004121), Ethanol (MESH:D000431), Cisplatin (MESH:D002945), copper (MESH:D003300), Sucrose (MESH:D013395)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), NIO-CIS-VOR — Homo sapiens (Human), Cutaneous melanoma, Cancer cell line (CVCL_AZ74), Pnac-1 — Mus musculus (Mouse), Hybridoma (CVCL_C7RB), HTB-38 — Mus musculus (Mouse), Hybridoma (CVCL_A8FQ), HCT29 — Homo sapiens (Human), Amyotrophic lateral sclerosis 1, Induced pluripotent stem cell (CVCL_8999), HT 29 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0320), PANC 1 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0480)

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## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC12880632/full.md

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Source: https://tomesphere.com/paper/PMC12880632