Abstract
Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with a worse prognosis than other types. There are currently no specific approved treatments for TNBC. Albumin is a promising biomimetic material that may be fabricated into nanoparticles to possibly exert passive effects on targeted tumors. Irinotecan has been extensively used in clinical settings, although a high dosage is required due to its low efficiency of conversion into the active metabolite SN-38, also known as 7-ethyl-10-hydroxy-camptothecin. The aim of this work was to optimize SN-38-loaded bovine serum albumin nanoparticles (sBSANPs) and evaluate their potency against TNBC. The sBSANPs were characterized by a small size of about 134–264 nm, a negative charge of −37 to −40 mV, an entrapment efficiency of 59–71%, and a particle yield of 65–86%. The cytotoxicity assays using sBSANPs showed a higher potency specifically against both MDA-MB-468 and MDA-MB-231 cells (ER−, PR−, HER2−) compared to MCF-7 (ER+, PR+, HER2−), and exhibited an extremely low IC50 at the nanomolar levels (2.01–6.82 nM). The release profiles indicated that SN-38 presented an initial burst release within 12 h, and sBSANPs had a slow release pattern. Flow cytometry results showed that the fluorescence intensity of sBSANPs was significantly higher than that of the control group. The confocal images also confirmed that sBSANPs were taken up by MDA-MB-468 cells. Moreover, we found that a larger BSANP size resulted in an increased hemolytic effect. In vivo animal studies demonstrated that loading of SN-38 into bovine serum albumin nanoparticles could minimize the initial concentration without extending the elimination half-life, but significantly minimized the Cmax (p < 0.001) as compared with irinotecan treatment.
Highlights
Triple-negative breast cancer (TNBC), by definition, refers to all breast cancers characterized by a lack estrogen, progesterone, and HER2 expression
Albumin nanoparticles without SN-38 (BSANP) were used to optimize these conditions
The results demonstrated that a range of 40–75 mg/mL corresponded to smaller particle sizes, and was adopted for the preparation of SN-38-loaded bovine serum albumin nanoparticles (sBSANPs)
Summary
Triple-negative breast cancer (TNBC), by definition, refers to all breast cancers characterized by a lack estrogen, progesterone, and HER2 expression. Chemotherapy-based regimens in adjuvant or neoadjuvant settings, anthracyclines, have been the choice of treatment prior to the advent of targeted therapy. Nab-paclitaxel, known as Abraxane® , is a product consisting of nanoparticles around 130 nm in size, and is indicated for metastatic breast cancer after the failure of combination chemotherapy for metastatic disease, which is common in the case of TNBC [2]. The combination of nab-paclitaxel and PD-L1 has resulted in a breakthrough in TNBC treatment by improving both progression-free and overall survival [3]. In this regard, albumin-based formulations continue to show their value and advance TNBC therapy
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