Abstract
Simple SummaryDoxorubicin (Dox) is a chemotherapeutic agent usually employed for the treatment of breast cancer. However, its use is limited because of the toxicities associated, and hence a proper delivery vehicle is necessary. In this sense, albumin-based nanocarriers are in the limelight for the successful delivery of chemotherapeutics because of safety, biocompatibility, and specific cancer-targeting properties. Herein, we have developed a nanocarrier system based on albumin, which selectively affects the tumor cells, and hence can revolutionize breast cancer therapy. The developed nanoparticles could be further used for the delivery of other hydrophobic drugs like SN38, which broadens the use of this system in the treatment of breast cancer.Albumin-based nanoparticles are an emerging platform for the delivery of various chemotherapeutics because of their biocompatibility, safety, and ease of surface modification for specific targeting. The most widely used method for the preparation of albumin nanoparticles is by desolvation process using glutaraldehyde (GLU) as a cross-linker. However, limitations of GLU like toxicity and interaction with drugs force the need for alternative cross-linkers. In the present study, several cross-linking systems were evaluated for the preparation of Bovine Serum Albumin (BSA) nanoparticles (ABNs) encapsulating Doxorubicin (Dox). Based on the results obtained from morphological characterization, in vitro release, and therapeutic efficacy in cells, N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP)-modified ABNs (ABN-SPDP) was chosen. Since ABN-SPDP are formed with disulfide linkage, the drug release is facilitated under a highly reducing environment present in the tumor sites. The cytotoxicity studies of those ABN-SPDP were performed in three different breast cell lines, highlighting the mechanism of cell death. The Dox-encapsulated ABN-SPDP showed toxicity in both the breast cancer cells (MCF-7 and MDA-MB-231), but, remarkably, a negligible effect was observed in non-tumoral MCF-10A cells. In addition to the hydrophilic Dox, this system could be used as a carrier for hydrophobic drugs like SN38. The system could be employed for the preparation of nanoparticles based on human serum albumin (HSA), which further enhances the feasibility of this system for clinical use. Hence, the albumin nanoparticles developed herein present an excellent potential for delivering various drugs in cancer therapy.
Highlights
Doxorubicin (Dox) is a widely used antineoplastic agent against various cancers, including breast cancer, Kaposi’s sarcoma, osteosarcoma, esophageal carcinoma, and Hodgkin’s and non-Hodgkin’s lymphomas [1]
GLU reacts with the amino groups on the surface of Bovine Serum Albumin (BSA) and cross-links the BSA molecules with each other
With the use of EDC as a cross-linker, a peptide bond is formed between the carboxyl and amide groups of BSA particles [24]
Summary
Doxorubicin (Dox) is a widely used antineoplastic agent against various cancers, including breast cancer, Kaposi’s sarcoma, osteosarcoma, esophageal carcinoma, and Hodgkin’s and non-Hodgkin’s lymphomas [1]. The nanoparticles facilitate the passive tumor targeting through enhanced permeation and retention (EPR) effect and overcome the problems associated with multidrug resistance [3,4]. In this regard, NPs based on albumin offer various advantages, including biocompatibility, safety, and convenient surface modification due to the presence of carboxylic and amino groups [5,6]. The development of albumin-based nanocarriers for drug delivery is interesting because of the various binding sites that facilitate incorporating hydrophilic and hydrophobic drugs in the particle matrix [9]
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