Erythrocyte Membrane-Wrapped pH Sensitive Polymeric Nanoparticles for Non-Small Cell Lung Cancer Therapy.

Abstract

The application of nano drug delivery systems (NDDSs) may enhance the effectiveness of chemotherapeutic drugs in vivo. However, the short blood circulation time and poor drug release profile in vivo are still two problems with them. Herein, by using red blood cell membrane (RBCm) wrapping and pH sensitive technology, we prepared RBCm wrapped pH sensitive poly(l-γ-glutamylcarbocistein)-paclitaxel (PGSC-PTX) nanoparticles (PGSC-PTX@RBCm NPs), to prolong the circulation time in blood and release PTX timely and adequately in acidic tumor environment. The PGSC-PTX NPs and PGSC-PTX@RBCm NPs showed spherical morphology with average sizes about 50 and 100 nm, respectively. The cytotoxicity of PGSC-PTX@RBCm NPs was considerably decreased compared with that of PGSC-PTX NPs. PTX release from PGSC-PTX and PGSC-PTX@RBCm NPs at pH 6.5 was remarkably higher than those at pH 7.4, respectively. The PGSC-PTX@RBCm NPs exhibited remarkably decreased uptake by macrophages than PGSC-PTX NPs. The area under the curve within 72 h (AUC0-72h) for is significantly higher than PGSC-PTX NPs. The PGSC-PTX@RBCm NPs also showed significantly stronger growth-inhibiting effect on tumor than PGSC-PTX NPs. These results indicated that PGSC-PTX@RBCm NPs have acidic drug release sensitivity, the characteristics of long circulation, and remarkable tumor growth inhibiting effect. This study may provide an effective strategy for improving the antitumor effect of NDDS.

• Authors: Lipeng Gao, Hao Wang, Lijuan Nan, Ting Peng, Lei Sun, Jinge Zhou, Ye Xiao, Jing Wang, Jihong Sun, Weiyue Lu, Lin Zhang, Zhiqiang Yan, Lei Yu, Yiting Wang
• Journal: Bioconjugate chemistry (Bioconjug Chem) Vol. 28 Issue 10 Pg. 2591-2598 (10 18 2017) ISSN: 1520-4812 [Electronic] United States
• PMID: 28872851 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drug Carriers
• Polymers
• poly(gamma-glutamylcarbocysteine)paclitaxel
• Polyglutamic Acid
• Paclitaxel

Topics

• Biological Transport
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Cell Line, Tumor
• Drug Carriers (chemistry, metabolism, pharmacokinetics, toxicity)
• Drug Liberation
• Erythrocyte Membrane (metabolism)
• Half-Life
• Hemolysis (drug effects)
• Humans
• Hydrogen-Ion Concentration
• Lung Neoplasms (drug therapy, pathology)
• Nanoparticles (chemistry)
• Paclitaxel (analogs & derivatives, chemistry, pharmacology, therapeutic use)
• Particle Size
• Polyglutamic Acid (analogs & derivatives, chemistry)
• Polymers (chemistry)