Development of ROS‐responsive amino acid‐based poly(ester amide) nanoparticle for anticancer drug delivery

Reactive oxygen species (ROS) play an important role in cellular metabolism and many oxidative stress related diseases. Oxidative stress results from toxic effects of ROS and plays a critical role in the pathogenesis of a variety of diseases like cancers and many important biological processes. It i...

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Veröffentlicht in:Journal of biomedical materials research. Part A 2021-04, Vol.109 (4), p.524-537
Hauptverfasser: Xu, Qinghua, Chu, Chih‐Chang
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description Reactive oxygen species (ROS) play an important role in cellular metabolism and many oxidative stress related diseases. Oxidative stress results from toxic effects of ROS and plays a critical role in the pathogenesis of a variety of diseases like cancers and many important biological processes. It is known that the unique feature of high intracellular ROS level in cancer cells can be considered as target and utilized as a useful cancer‐related stimulus to mediate intracellular drug delivery. Therefore, biomaterials responsive to excess level of ROS are of great importance in biomedical applications. In this study, a novel ROS‐responsive polymer based on L‐methionine poly(ester amide) (Met‐PEA‐PEG) was designed, synthesized, characterized and self‐assembled into nano‐micellar‐type nanoparticles (NP). The Met‐PEA‐PEG NP exhibited responsiveness to an oxidative environment. The size and morphology of the nanoparticle changed rapidly in the presence of H2O2. The Nile Red dye was loaded into the Met‐PEA‐PEG NP to demonstrate a H2O2 concentration induced time‐dependent release behavior. The Met‐PEA‐PEG NP was sensitive to high intracellular ROS level of PC3 prostate cancer cells. Furthermore, the Met‐PEA‐PEG NP was investigated as a carrier of a Chinese medicine‐based anticancer component, gambogic acid (GA). Compared to free GA, the GA‐loaded nanocomplex (GA‐NP) showed enhanced cytotoxicity toward PC3 and HeLa cells. The GA‐NP also induced a higher level of apoptosis and mitochondrial depolarization in PC3 cells than free GA. The Met‐PEA‐PEG NP improved the therapeutic effect of GA and may serve as a potential carrier for anticancer drug delivery.
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Furthermore, the Met‐PEA‐PEG NP was investigated as a carrier of a Chinese medicine‐based anticancer component, gambogic acid (GA). Compared to free GA, the GA‐loaded nanocomplex (GA‐NP) showed enhanced cytotoxicity toward PC3 and HeLa cells. The GA‐NP also induced a higher level of apoptosis and mitochondrial depolarization in PC3 cells than free GA. The Met‐PEA‐PEG NP improved the therapeutic effect of GA and may serve as a potential carrier for anticancer drug delivery.</abstract><cop>Hoboken, USA</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>32529749</pmid><doi>10.1002/jbm.a.37035</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-0530-3337</orcidid></addata></record>
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subjects Amino acids
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - pharmacology
Apoptosis
Biocompatibility
Biological activity
Biomaterials
Biomedical materials
Cancer
cancer therapy
Cytotoxicity
Delayed-Action Preparations - chemistry
Delayed-Action Preparations - metabolism
Depolarization
Drug delivery
Drug Delivery Systems
gambogic acid
HeLa Cells
Herbal medicine
Humans
Hydrogen peroxide
Intracellular
L‐methionine‐based poly(ester amide)
Methionine
Methionine - analogs & derivatives
Methionine - metabolism
Mitochondria
Morphology
nanoparticle
Nanoparticles
Nanoparticles - chemistry
Nanoparticles - metabolism
Neoplasms - drug therapy
Neoplasms - metabolism
Oxidative metabolism
Oxidative stress
Pathogenesis
PC-3 Cells
Polyesteramides
Polyesters - chemistry
Polyesters - metabolism
Polyethylene glycol
Polymers
Prostate cancer
Reactive oxygen species
Reactive Oxygen Species - metabolism
ROS‐responsive
Toxicity
Xanthones - administration & dosage
Xanthones - pharmacology
title Development of ROS‐responsive amino acid‐based poly(ester amide) nanoparticle for anticancer drug delivery
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