Project background

Amphiphilic block copolymers used as nanomicelle drug carriers can effectively overcome poor drug solubility and specificity issues. Hence, these platforms have a broad applicability in cancer treatment. We have developed Pluronic F127 nanomicelles containing the histone deacetylase inhibitor SAHA, which has an epigenetic-driven anti-cancer effect in several tumor types. SAHA-loaded nanomicelles were prepared using a thin-film drying method and characterized for size, surface charge, drug content, and drug release properties. Loaded particles were tested for in vitro activity and were effective on blocking cell cycle and markers of cancer progression.

Technology summary

Pluronic is a water-soluble amphiphilic molecule with a poly(oxyethylene)-block-poly (oxypropylene)-block-poly(oxyethylene) (PEOx–PPOy–PEOz) triblock structure (Farrugia et al. 2014), which self-assembles forming core–shell micelles in aqueous media. We have shown that the HDAC inhibitor SAHA can be efficiently loaded into pluronic F127 nanomicelles. We demonstrated that SAHA-loaded nanomicelles are able to efficiently release the drug in a time-dependent fashion. SAHA nanomicelles were shown to be more efficient than the free drug in reducing cell viability and inhibiting cell migration capacities of breast and cervical cancer cell lines, which represent two cancer types that still require more effective, epigenetic-based, treatments. Cellular uptake studies demonstrated the effective micellular uptake and intracellular distribution in a cell line-dependent fashion. In addition, the encapsulated SAHA remained effective in triggering cell cycle arrest and apoptosis in a dosage-dependent manner. The HDAC inhibitor also altered the expression of the EMT markers E-cadherin and N-cadherin, suggesting that effective delivery has the potential to reverse the aggressive, metastatic phenotype of these cancer models.

Benefits/Advantages

Encapsulation of SAHA into nanomicelles enhances the potency of this epigenetic drug in breast and cervical cancer cell models This effective formulation could enhance drug delivery to tumor sites, and overcome current issues in delivering HDAC inhibitors to solid tumors, while also reducing side-effects associated with systemic delivery of the free drug These effects are likely to be specific to different cancer types, as we found that the SAHA-loaded nanomicelles displayed different uptake rates, and directed intracellular trafficking in the two different cancer cell models.

Market application

As SAHA has been shown to cause harmful side-effects, encapsulation could be an effective route to reducing systemic toxicity Encapsulation could result in the use of less drug while still obtaining the required therapeutic effect, or more effective Encapsulation could result in tumor site specific delivery and uptake due to the inherent properties of nanostructures.

Ways of collaboration

· Joint technical collaboration. To date this project was a collaboration with Dr Chao Li at XJTU Nanoscience Academy Suzhou.