Prodigiosin/celecoxib-loaded into zein/sodium caseinate nanoparticles as a potential therapy for triple negative breast cancer

Sep 22, 2026

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Study evaluates encapsulating celecoxib (CXB) and prodigiosin (PDG) into zein/sodium caseinate nanoparticles to improve delivery against triple negative breast cancer. Nanoformulations yield homogenous, spherical nanoparticles with strong encapsulation efficiency and improved bioavailability. In vitro assays on MDA‑MB‑231 cells show lower IC50 for encapsulated drugs versus single agents or free combinations, with synergistic activity. Scratch wound healing and mechanistic profiling indicate enhanced antimigratory effects and apoptosis accompanied by reduced angiogenesis, proliferation, and inflammation, supporting nanoencapsulation as a promising multi‑drug therapeutic strategy.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Introduction

Background on breast cancer and therapy limitations

Celecoxib (CXB): COX-2 inhibition and anticancer pathways

Prodigiosin (PDG): anticancer mechanisms and bioavailability challenges

Rationale for combination and nanoencapsulation

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Prodigiosin/celecoxib‑loaded into zein/sodium caseinate nanoparticles as a potential therapy for triple negative breast cancer WafaaA. Mohamed, Nefertiti A. El‑Nekhily, Hoda E. Mahmoud, Ahmed A. Hussein & Sally A. Sabra * Nowadays, breast cancer is considered one of the most upsetting malignancies among females. Encapsulation of celecoxib (CXB) and prodigiosin (PDG) into zein/sodium caseinate nanoparticles (NPs) produce homogenous and spherical nanoparticles with good encapsulation efficiencies (EE %) and bioavailability. In vitro cytotoxicity study conducted on human breast cancer MDA‑MB‑231 cell lines revealed that there was a significant decline in the IC50 for encapsulated drugs when compared to each drug alone or their free combination. In addition, results demonstrated that there is a synergism between CXB and PDG as their combination indices were 0.62251 and 0.15493, respectively. Moreover, results of scratch wound healing assay revealed enhanced antimigratory effect of free drugs and fabricated NPs in comparison to untreated cells. Furthermore, In vitro results manifested that formulated nanoparticles exhibited induction of apoptosis associated with reduced angiogenesis, proliferation, and inflammation. In conclusion, nanoencapsulation of multiple drugs into nanoparticles might be a promising approach to develop new therapies for the managing of triple negative breast cancer. Globally, Breast cancer is the most frequent cancer among females and the second leading cause of mortality after lung cancer1. In 2018, breast cancer caused more than 7000 deaths and more than 100,000 new cases were diagnosed2. This disorder is a multifactorial disease in which many risk factors might contribute to its progression3. The first line therapy for breast cancer is usually chemotherapy which can be administrated solely or in combination with radiation or surgery4. However, chemotherapeutic drugs usually have several drawbacks including; drug resistance, recurrence and diverse systemic negative side effects5. Consequently, there is a great demand to develop new therapy regimens with new drugs such as multi-target inhibitors which could be a single drug with multiple inhibitory effects or combinational therapy of more than one drug so as to simultaneously hit more than one pathway all at once6. Celecoxib (CXB); 4-[5-(4-methylphenyl)–3-(trifluoromethyl)-1H-pyrazol-1-yl] benzene sulfonamide, is a well-known anti-inflammatory drug, selective COX-2 inhibitor and non-steroidal anti-inflammatory drug (NSAID)7. It is available in the market in an oral dosage form which was initially approved by the FDA and it was launched by Pfizer, Inc. (New York, NY, USA) in 19998. Cyclooxygenase 2 (COX-2) is well-known to be overexpressed in breast cancer cells leading to excessive conversion of arachidonic acid into prostaglandin E2 (PGE2). This reaction causes progression of breast cancer by several mechanisms including; antitumor immunity suppression, induction of proliferation and angiogenesis. COX-2 also plays a critical role in immune-suppression as it increases infiltration of CD8+ in breast cancer tissue9. Meanwhile, it was previously reported that inhibition of COX-2 causes induction of apoptosis via activating caspase 3 and suppressing survivin which is an antiapoptotic protein10, 11. CXB exerts its antitumor effect on different breast cancer cell lines depending upon COX-2 (the main inflammatory marker) by inhibiting cell growth and blood supply to tumor cells12. CXB is also able to inhibit canonical Wnt/β_Catenin pathway and PI3-K/PDK1/Akt pathway which in turn can inhibit cancer cell survival, angiogenesis, proliferation and migration13, 14. Moreover, CXB can induce apoptosis by both COX-2 Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria 21526, Egypt.*[email: ssabra@uwo.ca](email: ssabra@uwo.ca); [ss

FAQs

Why use nanoparticles to deliver celecoxib and prodigiosin in triple negative breast cancer?

To improve encapsulation, bioavailability, and therapeutic performance compared with free drugs, while enabling simultaneous targeting through combination action.

What do the in vitro cytotoxicity results show for encapsulated CXB/PDG versus free drugs?

Encapsulated formulations produce a significant IC50 reduction on MDA‑MB‑231 cells compared with each drug alone or their free combination.

What additional effects beyond cytotoxicity were observed in the study?

Scratch wound healing assays show enhanced antimigratory effects, and formulated nanoparticles induce apoptosis linked with reduced angiogenesis, proliferation, and inflammation.

Sep 22, 2026

Upload by Jiven