Investigation of cell death mechanism and activity of esculetin-loaded PLGA nanoparticles on insulinoma cellsin vitro

Abstract

Aim The purpose of this study was to prepare targeted cancer therapy formulation against insulinoma INS‐1 cells and to study its effect on cell death with related mechanisms in vitro. Methods Polylactide‐co‐glycolide (PLGA) nano‐micelles were used for preparation of esculetin nano‐formulation (nano‐esculetin). The cells were treated with nano‐esculetin and free esculetin. Apoptotic and necrotic cell death percentages, cell proliferation, ATP and GTP reductions and insulin levels were investigated on insulinoma INS‐1 cells for both free and nano‐esculetin formulations. Results About 50 mg of PLGA was able to carry 20 mg esculetin in 20 ml of formulation. The obtained optimized formulation was 150 nm, with 92% encapsulation efficiency and a slow‐release behaviour was observed during release studies. Nano‐esculetin bearing 25, 50 and 100 μg esculetin and free esculetin in equivalent doses successfully decreased cell viability. The prevailing cell death mechanism was necrosis. Along with cell proliferation, intracellular insulin and the ratio of ATP and GTP were decreased even with 12.5, 25 and 50 μg esculetin bearing nano‐formulation and its equivalent free esculetin. Conclusions The results revealed that esculetin is able to show its anti‐tumor afficacy after loading to PLGA nano‐micelles and nano‐encapsulation intensifies its cytotoxic activity in vitro. Current study shows that esculetin and its nano formulations are promising agents in treatment of insulinoma.

Esculetin unveiled: Decoding its anti‐tumor potential through molecular mechanisms—A comprehensive review

“…90 According to the findings, esculetin can exhibit anti-tumor activity after being loaded into PLGA nano-micelles, and nanoencapsulation increases its cytotoxic action in vitro with 92% encapsulation efficiency. 90 Lu et al stated that the electrochemical response of esculetin was significantly improved by the addition of CdSe NPs to PDDA-G over a range from 1.0 Â 10 À8 to 5.0 Â 10 À5 mol L À1 with a detection limit of 4.0 Â 10 À9 mol L À1 (S/N = 3). 91 Administration of esculetin with zinc oxide nanoparticles elevated caspase-3 expression.…”

“…Formulating anticancer agents like esculetin into nano‐sized particles can significantly improve their efficacy. The research was carried out to examine the impact of nano‐esculetin on insulinoma INS‐1 cells, with an in vitro assessment of its effect on cell death and associated mechanisms 90 . According to the findings, esculetin can exhibit anti‐tumor activity after being loaded into PLGA nano‐micelles, and nano‐encapsulation increases its cytotoxic action in vitro with 92% encapsulation efficiency 90 .…”

“…The research was carried out to examine the impact of nano‐esculetin on insulinoma INS‐1 cells, with an in vitro assessment of its effect on cell death and associated mechanisms 90 . According to the findings, esculetin can exhibit anti‐tumor activity after being loaded into PLGA nano‐micelles, and nano‐encapsulation increases its cytotoxic action in vitro with 92% encapsulation efficiency 90 . Lu et al stated that the electrochemical response of esculetin was significantly improved by the addition of CdSe NPs to PDDA‐G over a range from 1.0 × 10 −8 to 5.0 × 10 −5 mol L −1 with a detection limit of 4.0 × 10 −9 mol L −1 ( S / N = 3) 91 .…”

Coumarins and Coumarin-Related Compounds in Pharmacotherapy of Cancer

“…Free esculetin also decreased the viability of cells in vitro; however, it has been known that nano-formulations exhibit their superior efficacy at in vivo conditions due to enhanced permeability and retention (EPR) effect. Therefore, nano-formulation of esculetin is thought to be more effective than free esculetin at in vivo conditions [88].…”

Artemisia scoparia and Metabolic Health: Untapped Potential of an Ancient Remedy for Modern Use

“…These include lung injury and fibrosis ( 356 , 357 , 520 ); fibromyalgia ( 521 ); neuronal oxidative stress ( 522 ); psoriasis ( 523 ); arthritis ( 358 ); nociception ( 359 ); colitis ( 360 ); allergy, immunity, and asthma ( 282 , 354 , 380 – 383 ); and sepsis ( 361 ). The effects of esculetin on numerous cancer cell types have been extensively studied ( 94 , 321 – 342 , 519 , 524 , 525 ) and are the basis for efforts to develop novel therapeutics ( 98 , 341 ). Neuroprotective and behavioral actions of esculetin have also been described ( 111 , 299 , 367 – 371 , 526 – 528 ).…”