Dual peptide-modified nanoparticles improve combination chemotherapy of etoposide and siPIK3CA against drug-resistant small cell lung carcinoma
Journal
Pharmaceutics
Journal Volume
12
Journal Issue
3
Pages
254
Date Issued
2020
Author(s)
Huang H.-L.
Abstract
Small cell lung carcinoma (SCLC) is a highly aggressive form of malignancy with rapid recurrence and poor prognosis. The dual peptide-modified nanoparticles (NPs) for improving chemotherapy against drug-resistant small cell lung carcinoma cells has been developed. In this study, the SCLC targeting ligand, antagonist G peptide (AG), and cell-penetrating peptide, TAT, modified NPs were used to encapsulate both anticancer drugs etoposide (ETP) and PIK3CA small-interfering RNA (siPIK3CA). The ETP@NPs and siRNA@NPs had particle size 201.0 ± 1.9-206.5 ± 0.7 nm and 155.3 ± 12.4-169.1 ± 11.2 nm, respectively. The lyophilized ETP@NPs and siRNA@NPs maintained their particle size and zeta potential during 28-day storage without severe aggregation or dissociation. Either ETP@NPs or siRNA@NPs significantly reduced the IC50 of drugs by 2.5–5.5 folds and 2.4–3.9 folds, respectively, as compared to free ETP and siRNA/PEI nanocomplex in drug-resistant CD133(+) H69 cells. Herein, the IC50 of dual-peptide modified ETP@NPs and siRNA@NPs were prominently lower than single-peptide modified NPs. The synergistic effect (CI < 1) was further observed in co-treatment of ETP and siPIK3CA particularly delivered by dual-peptide modified NPs. ? 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
Antagonist G peptide; Drug-resistance; Etoposide; SiPIK3CA; Small cell lung carcinoma
SDGs
Other Subjects
antagonist G peptide; antineoplastic agent; cell penetrating peptide; etoposide; nanoparticle; peptide derivative; PIK3CA small interfering RNA; small interfering RNA; TAT peptide; unclassified drug; Article; cancer combination chemotherapy; cell viability; controlled study; dispersity; drug cytotoxicity; drug stability; encapsulation; endocytosis; human; human cell; IC50; NCI-H69 cell line; particle size; small cell lung cancer; zeta potential
Type
journal article