<p>Combined Delivery of Temozolomide and siPLK1 Using Targeted Nanoparticles to Enhance Temozolomide Sensitivity in Glioma</p>

Abstract

Introduction: Temozolomide (TMZ) is the first-line chemotherapeutic option to treat glioma; however, its efficacy and clinical application are limited by its drug resistance properties. Polo-like kinase 1 (PLK1)-targeted therapy causes G2/M arrest and increases the sensitivity of glioma to TMZ. Therefore, to limit TMZ resistance in glioma, an angiopep-2 (A2)-modified polymeric micelle (A2PEC) embedded with TMZ and a small interfering RNA (siRNA) targeting PLK1 (siPLK1) was developed (TMZ-A2PEC/siPLK). Materials and Methods: TMZ was encapsulated by A2-PEG-PEI-PCL (A2PEC) through the hydrophobic interaction, and siPLK1 was complexed with the TMZ-A2PEC through electrostatic interaction. Then, an angiopep-2 (A2) modified polymeric micelle (A2PEC) embedding TMZ and siRNA targeting polo-like kinase 1 (siPLK1) was developed (TMZ-A2PEC/siPLK). Results: In vitro experiments indicated that TMZ-A2PEC/siPLK effectively enhanced the cellular uptake of TMZ and siPLK1 and resulted in significant cell apoptosis and cytotoxicity of glioma cells. In vivo experiments showed that glioma growth was inhibited, and the survival time of the animals was prolonged remarkably after TMZ-A2PEC/siPLK1 was injected via their tail vein. Discussion: The results demonstrate that the combination of TMZ and siPLK1 in A2PEC could enhance the efficacy of TMZ in treating glioma.

Angiopep-2-Modified Nanoparticles for Brain-Directed Delivery of Therapeutics: A Review

“…Moreover, the nanovector was designed with a redox-responsive feature to trigger the intracellular release of its payload. In the same year, a combination of Temozolomide and PLK1 siRNA by Angiopep-2-modified PEG-PEI-PCL micelles produced enhanced drug efficacy in glioma [133].…”

The LncRNA DUXAP10 Could Function as a Promising Oncogene in Human Cancer

“…Gliomas are the most common primary malignancy of the central nervous system (Briançon-Marjollet et al, 2010;Deluche et al, 2019;Shi et al, 2020a). DUXAP10 has been indicated to be highly expressed in glioma cell lines (HS683, U251, U373, U87, T98G LN-319, and SW1783 cells) and tissues gained from patients under surgery at the First Affiliated Hospital of Jinan University.…”

“…Cell proliferation and apoptosis are fundamental for normal cell growth and development. Abnormal cell growth is a key marker for cancer (Shi et al, 2020a;Go et al, 2021;. It has been shown that microRNA-1914 could increase the effect of DUXAP10 on cell proliferation and apoptosis through activation of the GPR39-mediated PI3K/AKT/mTOR pathway in HCC Hep3B and MHCC-97L (Sun et al, 2019) cells (Figure 2).…”

Role of Calixarene in Chemotherapy Delivery Strategies

“…To achieve effective anticancer effects, high doses of TMZ must be administered resulting in severe side effects [ 57 ]. For these reasons, previous works have already demonstrated the possibility of stabilizing TMZ through its encapsulation in both nanoparticles and nanoliposomes [ 76 , 77 ]. Among the many possibilities, the encapsulation of TMZ in amphiphilic nanoparticles demonstrates greater stability compared to the free drug, based on chitosan and polylactic enriched with carboxy acids [ 78 ].…”