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Efficient Delivery of Antitumor Drug to the Nuclei of Tumor Cells by Amphiphilic Biodegradable Poly( L ‐Aspartic Acid‐ co ‐Lactic Acid)/DPPE Co‐Polymer Nanoparticles

The use of biodegradable polymeric nanoparticles (NPs) for controlled drug delivery has shown significant therapeutic potential. Polyaspartic acid and polylactic acid are the most intensively studied biodegradable polymers. In the present study, novel amphiphilic biodegradable co‐polymer NPs, poly(‐... Full description

Journal Title: Small 21 May 2012, Vol.8(10), pp.1596-1606
Main Author: Han, Siyuan
Other Authors: Liu, Yuexian , Nie, Xin , Xu, Qing , Jiao, Fang , Li, Wei , Zhao, Yuliang , Wu, Yan , Chen, Chunying
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 1613-6810 ; E-ISSN: 1613-6829 ; DOI: 10.1002/smll.201102280
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recordid: wj10.1002/smll.201102280
title: Efficient Delivery of Antitumor Drug to the Nuclei of Tumor Cells by Amphiphilic Biodegradable Poly( L ‐Aspartic Acid‐ co ‐Lactic Acid)/DPPE Co‐Polymer Nanoparticles
format: Article
creator:
  • Han, Siyuan
  • Liu, Yuexian
  • Nie, Xin
  • Xu, Qing
  • Jiao, Fang
  • Li, Wei
  • Zhao, Yuliang
  • Wu, Yan
  • Chen, Chunying
subjects:
  • Biodegradable Co‐Polymers
  • Nanoparticles
  • Controlled Drug Release
  • Nucleus‐Targeted Drug Delivery
  • Tumor Inhibition
ispartof: Small, 21 May 2012, Vol.8(10), pp.1596-1606
description: The use of biodegradable polymeric nanoparticles (NPs) for controlled drug delivery has shown significant therapeutic potential. Polyaspartic acid and polylactic acid are the most intensively studied biodegradable polymers. In the present study, novel amphiphilic biodegradable co‐polymer NPs, poly(‐aspartic acid‐‐lactic acid) with 1,2‐dipalmitoyl‐‐glycero‐3‐phosphoethanolamine (DPPE) (poly(AA‐co‐LA)/DPPE) is synthesized and subsequently used to encapsulate an antitumor drug doxorubicin (DOX). The formulation parameters of the NPs are optimized to improve encapsulation efficiency. The resulting drug‐loaded NPs possess better size homogeneity (polydispersity) and exhibit pH‐responsive drug release profiles. Cellular viability assays indicate that the poly(AA‐co‐LA)/DPPE NPs did not induce cell death, whereas doxorubicin encapsulated NPs were cytotoxic to various types of tumor cells. In addition, the free NPs could not enter the cell nuclei after internalized in tumor cells. The DOX‐loaded NPs exhibit efficient intracellular delivery in tumor cells with co‐localization in lysosome and delay entering into the nucleus, which suggests a time‐ and pH‐dependent drug release profile within cells. When applied to deliver chemotherapeutics to a mouse xenograft model of human lung adenocarcinoma, DOX‐loaded NPs have a comparable antitumor activity with free DOX, and greatly reduce systemic toxicity and mortality. The delivery of cytotoxic drugs directly to the nucleus specifically within tumor cells is of great interest. These results demonstrate the feasibility of the application of the amphiphilic polyaspartic acid derivative, poly(AA‐co‐LA)/DPPE, as a nanocarrier for cell nuclear delivery of potent antitumor drugs. poly(aspartic acid (AA)‐‐lactic acid (LA))/DPPE co‐polymer is synthesized and used to prepare doxorubicin (DOX)‐loaded nanoparticles for tumor therapy. These nanoparticles are prepared by double emulsion method and exhibit pH‐responsive drug release profiles. It is of great interest that these poly(AA‐‐LA)/DPPE nanoparticles can efficiently deliver a chemotherapy drug DOX into the nuclei specifically within tumor cells and show dose‐ and time‐dependent cytotoxicity.
language: eng
source:
identifier: ISSN: 1613-6810 ; E-ISSN: 1613-6829 ; DOI: 10.1002/smll.201102280
fulltext: fulltext
issn:
  • 1613-6810
  • 16136810
  • 1613-6829
  • 16136829
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titleEfficient Delivery of Antitumor Drug to the Nuclei of Tumor Cells by Amphiphilic Biodegradable Poly( L ‐Aspartic Acid‐ co ‐Lactic Acid)/DPPE Co‐Polymer Nanoparticles
creatorHan, Siyuan ; Liu, Yuexian ; Nie, Xin ; Xu, Qing ; Jiao, Fang ; Li, Wei ; Zhao, Yuliang ; Wu, Yan ; Chen, Chunying
ispartofSmall, 21 May 2012, Vol.8(10), pp.1596-1606
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subjectBiodegradable Co‐Polymers ; Nanoparticles ; Controlled Drug Release ; Nucleus‐Targeted Drug Delivery ; Tumor Inhibition
descriptionThe use of biodegradable polymeric nanoparticles (NPs) for controlled drug delivery has shown significant therapeutic potential. Polyaspartic acid and polylactic acid are the most intensively studied biodegradable polymers. In the present study, novel amphiphilic biodegradable co‐polymer NPs, poly(‐aspartic acid‐‐lactic acid) with 1,2‐dipalmitoyl‐‐glycero‐3‐phosphoethanolamine (DPPE) (poly(AA‐co‐LA)/DPPE) is synthesized and subsequently used to encapsulate an antitumor drug doxorubicin (DOX). The formulation parameters of the NPs are optimized to improve encapsulation efficiency. The resulting drug‐loaded NPs possess better size homogeneity (polydispersity) and exhibit pH‐responsive drug release profiles. Cellular viability assays indicate that the poly(AA‐co‐LA)/DPPE NPs did not induce cell death, whereas doxorubicin encapsulated NPs were cytotoxic to various types of tumor cells. In addition, the free NPs could not enter the cell nuclei after internalized in tumor cells. The DOX‐loaded NPs exhibit efficient intracellular delivery in tumor cells with co‐localization in lysosome and delay entering into the nucleus, which suggests a time‐ and pH‐dependent drug release profile within cells. When applied to deliver chemotherapeutics to a mouse xenograft model of human lung adenocarcinoma, DOX‐loaded NPs have a comparable antitumor activity with free DOX, and greatly reduce systemic toxicity and mortality. The delivery of cytotoxic drugs directly to the nucleus specifically within tumor cells is of great interest. These results demonstrate the feasibility of the application of the amphiphilic polyaspartic acid derivative, poly(AA‐co‐LA)/DPPE, as a nanocarrier for cell nuclear delivery of potent antitumor drugs. poly(aspartic acid (AA)‐‐lactic acid (LA))/DPPE co‐polymer is synthesized and used to prepare doxorubicin (DOX)‐loaded nanoparticles for tumor therapy. These nanoparticles are prepared by double emulsion method and exhibit pH‐responsive drug release profiles. It is of great interest that these poly(AA‐‐LA)/DPPE nanoparticles can efficiently deliver a chemotherapy drug DOX into the nuclei specifically within tumor cells and show dose‐ and time‐dependent cytotoxicity.
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titleEfficient Delivery of Antitumor Drug to the Nuclei of Tumor Cells by Amphiphilic Biodegradable Poly( L ‐Aspartic Acid‐ co ‐Lactic Acid)/DPPE Co‐Polymer Nanoparticles
descriptionThe use of biodegradable polymeric nanoparticles (NPs) for controlled drug delivery has shown significant therapeutic potential. Polyaspartic acid and polylactic acid are the most intensively studied biodegradable polymers. In the present study, novel amphiphilic biodegradable co‐polymer NPs, poly(‐aspartic acid‐‐lactic acid) with 1,2‐dipalmitoyl‐‐glycero‐3‐phosphoethanolamine (DPPE) (poly(AA‐co‐LA)/DPPE) is synthesized and subsequently used to encapsulate an antitumor drug doxorubicin (DOX). The formulation parameters of the NPs are optimized to improve encapsulation efficiency. The resulting drug‐loaded NPs possess better size homogeneity (polydispersity) and exhibit pH‐responsive drug release profiles. Cellular viability assays indicate that the poly(AA‐co‐LA)/DPPE NPs did not induce cell death, whereas doxorubicin encapsulated NPs were cytotoxic to various types of tumor cells. In addition, the free NPs could not enter the cell nuclei after internalized in tumor cells. The DOX‐loaded NPs exhibit efficient intracellular delivery in tumor cells with co‐localization in lysosome and delay entering into the nucleus, which suggests a time‐ and pH‐dependent drug release profile within cells. When applied to deliver chemotherapeutics to a mouse xenograft model of human lung adenocarcinoma, DOX‐loaded NPs have a comparable antitumor activity with free DOX, and greatly reduce systemic toxicity and mortality. The delivery of cytotoxic drugs directly to the nucleus specifically within tumor cells is of great interest. These results demonstrate the feasibility of the application of the amphiphilic polyaspartic acid derivative, poly(AA‐co‐LA)/DPPE, as a nanocarrier for cell nuclear delivery of potent antitumor drugs. poly(aspartic acid (AA)‐‐lactic acid (LA))/DPPE co‐polymer is synthesized and used to prepare doxorubicin (DOX)‐loaded nanoparticles for tumor therapy. These nanoparticles are prepared by double emulsion method and exhibit pH‐responsive drug release profiles. It is of great interest that these poly(AA‐‐LA)/DPPE nanoparticles can efficiently deliver a chemotherapy drug DOX into the nuclei specifically within tumor cells and show dose‐ and time‐dependent cytotoxicity.
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abstractThe use of biodegradable polymeric nanoparticles (NPs) for controlled drug delivery has shown significant therapeutic potential. Polyaspartic acid and polylactic acid are the most intensively studied biodegradable polymers. In the present study, novel amphiphilic biodegradable co‐polymer NPs, poly(‐aspartic acid‐‐lactic acid) with 1,2‐dipalmitoyl‐‐glycero‐3‐phosphoethanolamine (DPPE) (poly(AA‐co‐LA)/DPPE) is synthesized and subsequently used to encapsulate an antitumor drug doxorubicin (DOX). The formulation parameters of the NPs are optimized to improve encapsulation efficiency. The resulting drug‐loaded NPs possess better size homogeneity (polydispersity) and exhibit pH‐responsive drug release profiles. Cellular viability assays indicate that the poly(AA‐co‐LA)/DPPE NPs did not induce cell death, whereas doxorubicin encapsulated NPs were cytotoxic to various types of tumor cells. In addition, the free NPs could not enter the cell nuclei after internalized in tumor cells. The DOX‐loaded NPs exhibit efficient intracellular delivery in tumor cells with co‐localization in lysosome and delay entering into the nucleus, which suggests a time‐ and pH‐dependent drug release profile within cells. When applied to deliver chemotherapeutics to a mouse xenograft model of human lung adenocarcinoma, DOX‐loaded NPs have a comparable antitumor activity with free DOX, and greatly reduce systemic toxicity and mortality. The delivery of cytotoxic drugs directly to the nucleus specifically within tumor cells is of great interest. These results demonstrate the feasibility of the application of the amphiphilic polyaspartic acid derivative, poly(AA‐co‐LA)/DPPE, as a nanocarrier for cell nuclear delivery of potent antitumor drugs. poly(aspartic acid (AA)‐‐lactic acid (LA))/DPPE co‐polymer is synthesized and used to prepare doxorubicin (DOX)‐loaded nanoparticles for tumor therapy. These nanoparticles are prepared by double emulsion method and exhibit pH‐responsive drug release profiles. It is of great interest that these poly(AA‐‐LA)/DPPE nanoparticles can efficiently deliver a chemotherapy drug DOX into the nuclei specifically within tumor cells and show dose‐ and time‐dependent cytotoxicity.
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pubWILEY‐VCH Verlag
doi10.1002/smll.201102280
pages1596-1606
date2012-05-21