Abstract
Background: The limitations of conventional treatment modalities in cancer, especially in breast cancer, facilitated the necessity for developing a safer drug delivery system (DDS). Inorganic nano-carriers based on calcium phosphates such as hydroxyapatite (HA) and carbonate apatite (CA) have gained attention due to their biocompatibility, reduced toxicity, and improved therapeutic efficacy. Methods: In this study, the potential of goose bone ash (GBA), a natural derivative of HA or CA, was exploited as a pH-responsive carrier to successfully deliver doxorubicin (DOX), an anthracycline drug into breast cancer cells (e.g., MCF-7 and MDA-MB-231 cells). GBA in either pristine form or in suspension was characterized in terms of size, morphology, functional groups, cellular internalization, cytotoxicity, pH-responsive drug (DOX) release, and protein corona analysis. Results: The pH-responsive drug release study demonstrated the prompt release of DOX from GBA through its disintegration in acidic pH (5.5–6.5), which mimics the pH of the endosomal and lysosomal compartments as well as the stability of GBA in physiological pH (pH 7.5). The result of DOX binding with GBA indicated an increment in binding affinity with increasing concentrations of DOX. Cell viability and cytotoxicity analysis showed no innate toxicity of GBA particles. Both qualitative and quantitative cellular uptake analysis in both cell lines displayed an enhanced cellular internalization of DOX-loaded GBA compared to free DOX molecules. The protein corona spontaneously formed on the surface of GBA particles exhibited its affinity toward transport proteins, structural proteins, and a few other selective proteins. The adsorption of transport proteins could extend the circulation half-life in biological environment and increase the accumulation of the drug-loaded NPs through the enhanced permeability and retention (EPR) effect at the tumor site. Conclusion: These findings highlight the potential of GBA as a DDS to successfully deliver therapeutics into breast cancer cells.
Highlights
Conventional chemotherapeutics has been a major impetus for breast cancer treatment, its adverse effects tend to limit their potentials
Large aggregates were observed for 0.1 mg/mL goose bone ash (GBA) suspension, whereas significantly fewer aggregates were detected for 0.01 mg/mL GBA suspension
Our findings demonstrated that GBA can enhance cellular internalization and drug-binding efficacy when used as a carrier
Summary
Conventional chemotherapeutics has been a major impetus for breast cancer treatment, its adverse effects tend to limit their potentials. Nanoparticle-based drug delivery systems (NPDDSs) have emerged as competent carriers for therapeutic cargos They can (1) prolong circulation by increasing the uptake at the tumor site through the enhanced permeability and retention (EPR) effect, (2) provide tunable shape and size, (3) overcome multi-drug resistance (MDR) by avoiding p-glycoprotein recognition, (4) provide controlled release of drugs by different stimulus (e.g., pH, temperature, enzymes, biological or chemical agents), (5) prevent drug degradation, and (6) increase drug uptake in cancer cells [2,3,4,5,6]. It is of paramount importance to develop a new pH-responsive nano-carrier system with hallmarks including biodegradability, bioavailability, enhanced drug loading efficacy, and the prevention of premature drug leaking before the particles reach the site of action. Conclusion: These findings highlight the potential of GBA as a DDS to successfully deliver therapeutics into breast cancer cells
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