Effect of BN Nanoparticles Loaded with Doxorubicin on Tumor Cells with Multiple Drug Resistance

Abstract

Herein we study the effect of doxorubicin-loaded BN nanoparticles (DOX-BNNPs) on cell lines that differ in the multidrug resistance (MDR), namely KB-3-1 and MDR KB-8-5 cervical carcinoma lines, and K562 and MDR i-S9 leukemia lines. We aim at revealing the possible differences in the cytotoxic effect of free DOX and DOX-BNNP nanoconjugates on these types of cells. The spectrophotometric measurements have demonstrated that the maximum amount of DOX in the DOX-BNNPs is obtained after saturation in alkaline solution (pH 8.4), indicating the high efficiency of BNNPs saturation with DOX. DOX release from DOX-BNNPs is a pH-dependent and DOX is more effectively released in acid medium (pH 4.0-5.0). Confocal laser scanning microscopy has shown that the DOX-BNNPs are internalized by neoplastic cells using endocytic pathway and distributed in cell cytoplasm near the nucleus. The cytotoxic studies have demonstrated a higher sensitivity of the leukemia lines to DOX-BNNPs compared with the carcinoma lines: IC(DOX-BNNPs) is 1.13, 4.68, 0.025, and 0.14 μg/mL for the KB-3-1, MDR KB-8-5, K562, and MDR i-S9 cell lines, respectively. To uncover the mechanism of cytotoxic effect of nanocarriers on MDR cells, DOX distribution in both the nucleus and cytoplasm has been studied. The results indicate that the DOX-BNNP nanoconjugates significantly change the dynamics of DOX accumulation in the nuclei of both KB-3-1 and KB-8-5 cells. Unlike free DOX, the utilization of DOX-BNNPs nanoconjugates allows for maintaining a high and stable level of DOX in the nucleus of MDR KB-8-5 cells.

Preparation of Poly(lactic‐co‐glycolic acid)‐Based Composite Microfibers for Postoperative Treatment of Tumor in NIR I and NIR II Biowindows

“…However, free DOX has a poor therapeutic effect. In order to achieve a desirable therapeutic effect, a high drug dosage and repeated administration are required, which will cause drug loss, multi‐drug resistance, and side effects to patients . Various DOX‐carrier systems including micelles, liposomes, polymer drug conjugates, dendrimers, and micro‐ and nanoparticles have been developed to improve the antitumor therapeutic efficacy.…”

Plasma Surface Polymerized and Biomarker Conjugated Boron Nitride Nanoparticles for Cancer-Specific Therapy: Experimental and Theoretical Study

“…BNNPs were synthesized in a boron oxide CVD process using a vertical induction-heating furnace, operating at 41.4 kHz [28]. The furnace consisted of a quartz cylindrical chamber, graphite susceptor, BN-based ceramic reactor, gas supply, and exhaust gas systems.…”

“…Due to high chemical stability [21], different inorganic NPs, such as mesoporous silica [22], iron oxide [23], hexagonal boron nitride (h-BN) [24], and carbon nanotubes [25], have been developed and tested in NP-based cancer therapy. Among them, h-BN nanoparticles (BNNPs) are of particular interest due to their excellent biocompatibility [26], high drug loading capacity [27], and therapeutic efficacy toward tumor cells with multiple drug resistance [28].…”

In Vivo and In Vitro Anticancer Activity of Doxorubicin-loaded DNA-AuNP Nanocarrier for the Ovarian Cancer Treatment

“…However, there is still no systematic research on the in vivo anticancer activity of various Dox formulations for ovarian cancer treatment. Due to its intrinsic fluorescence and structural properties, Dox has been widely utilized for drug delivery studies as an imaging agent and anticancer drug in combination with nanodrug carriers such as inorganic nanoparticles [23][24][25], dendrimers [26][27][28], and graphene oxide [29,30], etc [31][32][33][34].…”