Development of gelatin nanoparticles conjugated with phytohemagglutinin erythroagglutinating loaded with gemcitabine for inducing apoptosis in non-small cell lung cancer cells

Wei Ting Kuo, Jian Yuan Huang, Min Hua Chen, Ching Yun Chen, Yan Jye Shyong, Ko Chung Yen, Yu Jun Sun, Cherng Jyh Ke, Yung Hsin Cheng, Feng Huei Lin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Gelatin is an efficient drug delivery vehicle for attaching targeting molecules like phytohemagglutinin erythroagglutinating (PHA-E) and carrying the chemotherapeutic agent gemcitabine (GEM). Fluorescent gelatin nanoparticles (GNPs) conjugated with PHA-E and carrying gemcitabine (GNP-(PHA-E)-GEM) were synthesized by nanoprecipitation for guiding gemcitabine-loaded gelatin nanoparticles to NSCLC by PHA-E targeting. GNPs have a uniform narrow size distribution and spherical shape, and their particle size is about 290 nm. The release rate of gemcitabine from nanoparticles reached the plateau of the curve at approximately 30% within 72 hours. PHA-E conjugated nanoparticles could enhance the cellular accumulation of nanoparticles. The results showed that GNP-(PHA-E)-GEM treatment caused an increase of cell growth inhibition and cytotoxicity on NSCLC cells A-549 and H292. In an Annexin V/PI assay, treatment with GNP-(PHA-E)-GEM could induce apoptosis of cancer cells. Treatment of NSCLC cells with GNP-(PHA-E)-GEM firstly resulted in time-dependent inhibition of epidermal growth factor receptor (EGFR) and Akt phosphorylation. And it also could increase p53 phosphorylation. And then it could decrease Bad phosphorylation and increase Bax. Finally, it could result in enhancing the release of cytochrome c, which thus increases caspase-9 and caspase-3. In conclusion, GNP-(PHA-E)-GEM could induce growth inhibition and cytotoxicity, which was mediated through inhibition of EGFR phosphorylation and the switching on of p53 that causes cell apoptosis of NSCLC cells A-549 and H292. It's significant to conjugate PHA-E for targeting cancer and inhibiting EGFR phosphorylation as it could decrease the dosage of gemcitabine, which reduces side effects on normal tissue. GNP-(PHA-E)-GEM has great potential for NSCLC treatment.

Original languageEnglish
Pages (from-to)2444-2454
Number of pages11
JournalJournal of Materials Chemistry B
Volume4
Issue number14
DOIs
Publication statusPublished - 2016 Apr 14

Fingerprint

gemcitabine
Cell death
Gelatin
Cells
Apoptosis
Nanoparticles
Phosphorylation
Epidermal Growth Factor Receptor
Cytotoxicity
erythroagglutinating phytohemagglutinin

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biomedical Engineering
  • Materials Science(all)

Cite this

Kuo, Wei Ting ; Huang, Jian Yuan ; Chen, Min Hua ; Chen, Ching Yun ; Shyong, Yan Jye ; Yen, Ko Chung ; Sun, Yu Jun ; Ke, Cherng Jyh ; Cheng, Yung Hsin ; Lin, Feng Huei. / Development of gelatin nanoparticles conjugated with phytohemagglutinin erythroagglutinating loaded with gemcitabine for inducing apoptosis in non-small cell lung cancer cells. In: Journal of Materials Chemistry B. 2016 ; Vol. 4, No. 14. pp. 2444-2454.
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abstract = "Gelatin is an efficient drug delivery vehicle for attaching targeting molecules like phytohemagglutinin erythroagglutinating (PHA-E) and carrying the chemotherapeutic agent gemcitabine (GEM). Fluorescent gelatin nanoparticles (GNPs) conjugated with PHA-E and carrying gemcitabine (GNP-(PHA-E)-GEM) were synthesized by nanoprecipitation for guiding gemcitabine-loaded gelatin nanoparticles to NSCLC by PHA-E targeting. GNPs have a uniform narrow size distribution and spherical shape, and their particle size is about 290 nm. The release rate of gemcitabine from nanoparticles reached the plateau of the curve at approximately 30{\%} within 72 hours. PHA-E conjugated nanoparticles could enhance the cellular accumulation of nanoparticles. The results showed that GNP-(PHA-E)-GEM treatment caused an increase of cell growth inhibition and cytotoxicity on NSCLC cells A-549 and H292. In an Annexin V/PI assay, treatment with GNP-(PHA-E)-GEM could induce apoptosis of cancer cells. Treatment of NSCLC cells with GNP-(PHA-E)-GEM firstly resulted in time-dependent inhibition of epidermal growth factor receptor (EGFR) and Akt phosphorylation. And it also could increase p53 phosphorylation. And then it could decrease Bad phosphorylation and increase Bax. Finally, it could result in enhancing the release of cytochrome c, which thus increases caspase-9 and caspase-3. In conclusion, GNP-(PHA-E)-GEM could induce growth inhibition and cytotoxicity, which was mediated through inhibition of EGFR phosphorylation and the switching on of p53 that causes cell apoptosis of NSCLC cells A-549 and H292. It's significant to conjugate PHA-E for targeting cancer and inhibiting EGFR phosphorylation as it could decrease the dosage of gemcitabine, which reduces side effects on normal tissue. GNP-(PHA-E)-GEM has great potential for NSCLC treatment.",
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Development of gelatin nanoparticles conjugated with phytohemagglutinin erythroagglutinating loaded with gemcitabine for inducing apoptosis in non-small cell lung cancer cells. / Kuo, Wei Ting; Huang, Jian Yuan; Chen, Min Hua; Chen, Ching Yun; Shyong, Yan Jye; Yen, Ko Chung; Sun, Yu Jun; Ke, Cherng Jyh; Cheng, Yung Hsin; Lin, Feng Huei.

In: Journal of Materials Chemistry B, Vol. 4, No. 14, 14.04.2016, p. 2444-2454.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Development of gelatin nanoparticles conjugated with phytohemagglutinin erythroagglutinating loaded with gemcitabine for inducing apoptosis in non-small cell lung cancer cells

AU - Kuo, Wei Ting

AU - Huang, Jian Yuan

AU - Chen, Min Hua

AU - Chen, Ching Yun

AU - Shyong, Yan Jye

AU - Yen, Ko Chung

AU - Sun, Yu Jun

AU - Ke, Cherng Jyh

AU - Cheng, Yung Hsin

AU - Lin, Feng Huei

PY - 2016/4/14

Y1 - 2016/4/14

N2 - Gelatin is an efficient drug delivery vehicle for attaching targeting molecules like phytohemagglutinin erythroagglutinating (PHA-E) and carrying the chemotherapeutic agent gemcitabine (GEM). Fluorescent gelatin nanoparticles (GNPs) conjugated with PHA-E and carrying gemcitabine (GNP-(PHA-E)-GEM) were synthesized by nanoprecipitation for guiding gemcitabine-loaded gelatin nanoparticles to NSCLC by PHA-E targeting. GNPs have a uniform narrow size distribution and spherical shape, and their particle size is about 290 nm. The release rate of gemcitabine from nanoparticles reached the plateau of the curve at approximately 30% within 72 hours. PHA-E conjugated nanoparticles could enhance the cellular accumulation of nanoparticles. The results showed that GNP-(PHA-E)-GEM treatment caused an increase of cell growth inhibition and cytotoxicity on NSCLC cells A-549 and H292. In an Annexin V/PI assay, treatment with GNP-(PHA-E)-GEM could induce apoptosis of cancer cells. Treatment of NSCLC cells with GNP-(PHA-E)-GEM firstly resulted in time-dependent inhibition of epidermal growth factor receptor (EGFR) and Akt phosphorylation. And it also could increase p53 phosphorylation. And then it could decrease Bad phosphorylation and increase Bax. Finally, it could result in enhancing the release of cytochrome c, which thus increases caspase-9 and caspase-3. In conclusion, GNP-(PHA-E)-GEM could induce growth inhibition and cytotoxicity, which was mediated through inhibition of EGFR phosphorylation and the switching on of p53 that causes cell apoptosis of NSCLC cells A-549 and H292. It's significant to conjugate PHA-E for targeting cancer and inhibiting EGFR phosphorylation as it could decrease the dosage of gemcitabine, which reduces side effects on normal tissue. GNP-(PHA-E)-GEM has great potential for NSCLC treatment.

AB - Gelatin is an efficient drug delivery vehicle for attaching targeting molecules like phytohemagglutinin erythroagglutinating (PHA-E) and carrying the chemotherapeutic agent gemcitabine (GEM). Fluorescent gelatin nanoparticles (GNPs) conjugated with PHA-E and carrying gemcitabine (GNP-(PHA-E)-GEM) were synthesized by nanoprecipitation for guiding gemcitabine-loaded gelatin nanoparticles to NSCLC by PHA-E targeting. GNPs have a uniform narrow size distribution and spherical shape, and their particle size is about 290 nm. The release rate of gemcitabine from nanoparticles reached the plateau of the curve at approximately 30% within 72 hours. PHA-E conjugated nanoparticles could enhance the cellular accumulation of nanoparticles. The results showed that GNP-(PHA-E)-GEM treatment caused an increase of cell growth inhibition and cytotoxicity on NSCLC cells A-549 and H292. In an Annexin V/PI assay, treatment with GNP-(PHA-E)-GEM could induce apoptosis of cancer cells. Treatment of NSCLC cells with GNP-(PHA-E)-GEM firstly resulted in time-dependent inhibition of epidermal growth factor receptor (EGFR) and Akt phosphorylation. And it also could increase p53 phosphorylation. And then it could decrease Bad phosphorylation and increase Bax. Finally, it could result in enhancing the release of cytochrome c, which thus increases caspase-9 and caspase-3. In conclusion, GNP-(PHA-E)-GEM could induce growth inhibition and cytotoxicity, which was mediated through inhibition of EGFR phosphorylation and the switching on of p53 that causes cell apoptosis of NSCLC cells A-549 and H292. It's significant to conjugate PHA-E for targeting cancer and inhibiting EGFR phosphorylation as it could decrease the dosage of gemcitabine, which reduces side effects on normal tissue. GNP-(PHA-E)-GEM has great potential for NSCLC treatment.

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