Anti-CD44 and EGFR Dual-Targeted Solid Lipid Nanoparticles for Delivery of Doxorubicin to Triple-Negative Breast Cancer Cell Line: Preparation, Statistical Optimization, and In Vitro Characterization

Abstract

Background. Despite being more aggressive than other types of breast cancer, there is no suitable treatment for triple-negative breast cancer (TNBC). Here, we designed doxorubicin-containing solid lipid nanoparticles (SLNs) decorated with anti-EGFR/CD44 dual-RNA aptamers, which are overexpressed in TNBC. For more efficiency in the nuclear delivery of doxorubicin, dexamethasone (Dexa) was chemically attached to the surface of nanoparticles. Methods. To prepare the cationic SLNs, 6-lauroxyhexyl BOC-ornithine (LHON) was synthesized and was chemically attached to dexamethasone to form Dexa-LHON complexes. The doxorubicin-containing SLNs were prepared via double emulsification ( w / o / w ) and the solvent evaporation technique. The preparation of SLNs was statistically optimized using the central composite response surface methodology. Independent factors were the GMS/lecithin concentration ratio and the amount of Tween 80, while responses considered were particle size, polydispersity index, and entrapment efficiency of the nanoparticles. The optimized nanoparticles were studied morphologically using transmission electron microscopy, and in vitro release of doxorubicin from nanoparticles was studied in phosphate-buffered saline. Then, the designated aptamers were attached to the surface of nanoparticles using electrostatic interactions, and their cytotoxicity was assessed in vitro. Results. The size, PDI, zeta potential, EE%, and LE% of the prepared nanoparticles were 101 ± 12.6 nm , 0.341 ± 0.005 , + 13.6 ± 1.83 mV , 69.98 ± 7.54 % , and 10.2 ± 1.06 % , respectively. TEM images revealed spherical nanoparticles with no sign of aggregation. In vitro release study exhibited that 96.1 ± 1.97 % of doxorubicin was released within 48 h of incubation. The electrostatic attachment of the designated aptamers to the nanoparticles’ surface was confirmed by reducing the zeta potential to − 15.6 ± 2.07 mV . The in vitro experiments revealed that the SLNs/DOX/Dexa/CD44 or EGFR aptamers were substantially more successful than SLNs/DOX/Dexa at inhibiting cell proliferation. Using the MDA-MB-468 cell line, we discovered that SLN/DOX/Dexa/CD44/EGFR aptamers were more effective than other constructs in inhibiting cell proliferation ( p < 0.001 ). The reduction of cell viability using this construct suggests that targeting numerous proliferation pathways is effective. Conclusion. Overall, the finding of this investigation suggested that SLNs/DOX/Dexa/CD44/EGFR could be a promising new enhanced anticancer delivery system and deserved further preclinical consideration.

Aptamers: Features, Synthesis and Applications

“…TNBC is an aggressive and fatal breast tumor and poor prognosis and metastasis occur more in this subtype than other subtypes even though the TNBC only contributes 15–20 % of breast cancer cell types. The findings demonstrated that the two‐aptamer‐containing system is a promising strategy for combination therapy [92] . Figure 6 is the schematic representation of a DOX encapsulated in surface modified solid lipid nanoparticles with dual targeting EGFR and CD44 RNA aptamers”.…”

“…The findings demonstrated that the two-aptamer-containing system is a promising strategy for combination therapy. [92] Figure 6 is the schematic representation of a DOX encapsulated in surface modified solid lipid nanoparticles with dual targeting EGFR and CD44 RNA aptamers".…”

“…Drug Target A15 Salinomycin Hepatocellular cancer [91] CD44 RNA DOX Triple negative breast cancer [92] MUC1 DOX MUC1 positive cancer cells [93] C2NP DOX ALCL [98] AS1411 DOX ChemoÀ PTT [99] Gint4 DOX PDGFRβ [100] AS1411 5-FU Nucleolin [101]…”

DNA-Based Nanomaterials as Drug Delivery Platforms for Increasing the Effect of Drugs in Tumors

“…Dexamethasone was chemically attached to the surface of the nanoparticles for more efficient delivery of doxorubicin to the nucleus of MDA-MB-468 cells. It was found that this designed nanoparticle was more effective than its components alone in inhibiting MDA-MB-468 cell proliferation [ 94 ].…”

Single-atom nanozymes: From bench to bedside

“…According to the recent statistics of the International Agency for Research on Cancer, breast cancer has become the most diagnosed cancer in both sexes [87]. Much attention has been paid to develop novel materials for breast cancer treatment [88][89][90][91]. Recently, increasing number of studies have shown the efficiency of single-atom nanozymes in breast cancer therapy.…”