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Open AccessArticle

Dual Peptide-Modified Nanoparticles Improve Combination Chemotherapy of Etoposide and siPIK3CA Against Drug-Resistant Small Cell Lung Carcinoma

by Hsin-Lin Huang 1 and Wen Jen Lin 1,2,*
1
School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10050, Taiwan
2
Drug Research Center, College of Medicine, National Taiwan University, Taipei 10050, Taiwan
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(3), 254; https://doi.org/10.3390/pharmaceutics12030254
Received: 26 February 2020 / Revised: 9 March 2020 / Accepted: 10 March 2020 / Published: 12 March 2020
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 [email protected] and [email protected] 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 [email protected] and [email protected] maintained their particle size and zeta potential during 28-day storage without severe aggregation or dissociation. Either [email protected] or [email protected] 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 [email protected] and [email protected] 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. View Full-Text
Keywords: small cell lung carcinoma; drug-resistance; antagonist G peptide; etoposide; siPIK3CA small cell lung carcinoma; drug-resistance; antagonist G peptide; etoposide; siPIK3CA
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MDPI and ACS Style

Huang, H.-L.; Lin, W.J. Dual Peptide-Modified Nanoparticles Improve Combination Chemotherapy of Etoposide and siPIK3CA Against Drug-Resistant Small Cell Lung Carcinoma. Pharmaceutics 2020, 12, 254.

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