PH-dependent, thermosensitive polymeric nanocarriers for drug delivery to solid tumors

Ching Yi Chen; Tae Hee Kim; Wen Chung Wu; Chi Ming Huang; Hua Wei; Christopher W. Mount; Yanqing Tian; Sei Hum Jang; Suzie H. Pun; Alex K Y Jen

doi:10.1016/j.biomaterials.2013.02.049

PH-dependent, thermosensitive polymeric nanocarriers for drug delivery to solid tumors

Ching Yi Chen, Tae Hee Kim, Wen Chung Wu, Chi Ming Huang, Hua Wei, Christopher W. Mount, Yanqing Tian, Sei Hum Jang, Suzie H. Pun, Alex K Y Jen

Research output: Contribution to journal › Article › peer-review

132 Scopus citations

Abstract

Polymeric micelles are promising carriers for anti-cancer agents due to their small size, ease of assembly, and versatility for functionalization. A current challenge in the use of polymeric micelles is the sensitive balance that must be achieved between stability during prolonged blood circulation and release of active drug at the tumor site. Stimuli-responsive materials provide a mechanism for triggered drug release in the acidic tumor and intracellular microenvironments. In this work, we synthesized a series of dual pH- and temperature-responsive block copolymers containing a poly(ε-caprolactone) (PCL) hydrophobic block with a poly(triethylene glycol) block that were copolymerized with an amino acid-functionalized monomer. The block copolymers formed micellar structures in aqueous solutions. An optimized polymer that was functionalized with 6-aminocaproic acid (ACA) possessed pH-sensitive phase transitions at mildly acidic pH and body temperature. Doxorubicin-loaded micelles formed from these polymers were stable at blood pH (~7.4) and showed increased drug release at acidic pH. In addition, these micelles displayed more potent anti-cancer activity than free doxorubicin when tested in a tumor xenograft model in mice.

Original language	English (US)
Pages (from-to)	4501-4509
Number of pages	9
Journal	Biomaterials
Volume	34
Issue number	18
DOIs	https://doi.org/10.1016/j.biomaterials.2013.02.049
State	Published - Jun 2013

Keywords

Anti-cancer
PH-sensitive
Polymeric micelle
Temperature sensitive
Tumor delivery

ASJC Scopus subject areas

Biophysics
Bioengineering
Ceramics and Composites
Biomaterials
Mechanics of Materials

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10.1016/j.biomaterials.2013.02.049

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@article{2cbf3c3a9c354a72af7203a9b4bb9642,

title = "PH-dependent, thermosensitive polymeric nanocarriers for drug delivery to solid tumors",

abstract = "Polymeric micelles are promising carriers for anti-cancer agents due to their small size, ease of assembly, and versatility for functionalization. A current challenge in the use of polymeric micelles is the sensitive balance that must be achieved between stability during prolonged blood circulation and release of active drug at the tumor site. Stimuli-responsive materials provide a mechanism for triggered drug release in the acidic tumor and intracellular microenvironments. In this work, we synthesized a series of dual pH- and temperature-responsive block copolymers containing a poly(ε-caprolactone) (PCL) hydrophobic block with a poly(triethylene glycol) block that were copolymerized with an amino acid-functionalized monomer. The block copolymers formed micellar structures in aqueous solutions. An optimized polymer that was functionalized with 6-aminocaproic acid (ACA) possessed pH-sensitive phase transitions at mildly acidic pH and body temperature. Doxorubicin-loaded micelles formed from these polymers were stable at blood pH (~7.4) and showed increased drug release at acidic pH. In addition, these micelles displayed more potent anti-cancer activity than free doxorubicin when tested in a tumor xenograft model in mice.",

keywords = "Anti-cancer, PH-sensitive, Polymeric micelle, Temperature sensitive, Tumor delivery",

author = "Chen, {Ching Yi} and Kim, {Tae Hee} and Wu, {Wen Chung} and Huang, {Chi Ming} and Hua Wei and Mount, {Christopher W.} and Yanqing Tian and Jang, {Sei Hum} and Pun, {Suzie H.} and Jen, {Alex K Y}",

note = "Funding Information: Support from the Microscale Life Sciences Center (MLSC)-A Center of Excellence in Genome Sciences funded by NIH is acknowledged. Alex K.-Y. Jen thanks the Boeing-Johnson Foundation for its support. Suzie Pun thanks the Washington Research Foundation for its support. W.-C. Wu thanks the financial support from National Science Council of Taiwan , R.O.C awarded for the research work at University of Washington ( NSC-096-2917-I-564-115 ). Christopher Mount was supported by a Levinson's Research Fellowship. ",

year = "2013",

month = jun,

doi = "10.1016/j.biomaterials.2013.02.049",

language = "English (US)",

volume = "34",

pages = "4501--4509",

journal = "Biomaterials",

issn = "0142-9612",

publisher = "Elsevier BV",

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TY - JOUR

T1 - PH-dependent, thermosensitive polymeric nanocarriers for drug delivery to solid tumors

AU - Chen, Ching Yi

AU - Kim, Tae Hee

AU - Wu, Wen Chung

AU - Huang, Chi Ming

AU - Wei, Hua

AU - Mount, Christopher W.

AU - Tian, Yanqing

AU - Jang, Sei Hum

AU - Pun, Suzie H.

AU - Jen, Alex K Y

N1 - Funding Information: Support from the Microscale Life Sciences Center (MLSC)-A Center of Excellence in Genome Sciences funded by NIH is acknowledged. Alex K.-Y. Jen thanks the Boeing-Johnson Foundation for its support. Suzie Pun thanks the Washington Research Foundation for its support. W.-C. Wu thanks the financial support from National Science Council of Taiwan , R.O.C awarded for the research work at University of Washington ( NSC-096-2917-I-564-115 ). Christopher Mount was supported by a Levinson's Research Fellowship.

PY - 2013/6

Y1 - 2013/6

N2 - Polymeric micelles are promising carriers for anti-cancer agents due to their small size, ease of assembly, and versatility for functionalization. A current challenge in the use of polymeric micelles is the sensitive balance that must be achieved between stability during prolonged blood circulation and release of active drug at the tumor site. Stimuli-responsive materials provide a mechanism for triggered drug release in the acidic tumor and intracellular microenvironments. In this work, we synthesized a series of dual pH- and temperature-responsive block copolymers containing a poly(ε-caprolactone) (PCL) hydrophobic block with a poly(triethylene glycol) block that were copolymerized with an amino acid-functionalized monomer. The block copolymers formed micellar structures in aqueous solutions. An optimized polymer that was functionalized with 6-aminocaproic acid (ACA) possessed pH-sensitive phase transitions at mildly acidic pH and body temperature. Doxorubicin-loaded micelles formed from these polymers were stable at blood pH (~7.4) and showed increased drug release at acidic pH. In addition, these micelles displayed more potent anti-cancer activity than free doxorubicin when tested in a tumor xenograft model in mice.

AB - Polymeric micelles are promising carriers for anti-cancer agents due to their small size, ease of assembly, and versatility for functionalization. A current challenge in the use of polymeric micelles is the sensitive balance that must be achieved between stability during prolonged blood circulation and release of active drug at the tumor site. Stimuli-responsive materials provide a mechanism for triggered drug release in the acidic tumor and intracellular microenvironments. In this work, we synthesized a series of dual pH- and temperature-responsive block copolymers containing a poly(ε-caprolactone) (PCL) hydrophobic block with a poly(triethylene glycol) block that were copolymerized with an amino acid-functionalized monomer. The block copolymers formed micellar structures in aqueous solutions. An optimized polymer that was functionalized with 6-aminocaproic acid (ACA) possessed pH-sensitive phase transitions at mildly acidic pH and body temperature. Doxorubicin-loaded micelles formed from these polymers were stable at blood pH (~7.4) and showed increased drug release at acidic pH. In addition, these micelles displayed more potent anti-cancer activity than free doxorubicin when tested in a tumor xenograft model in mice.

KW - Anti-cancer

KW - PH-sensitive

KW - Polymeric micelle

KW - Temperature sensitive

KW - Tumor delivery

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SN - 0142-9612

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EP - 4509

JO - Biomaterials

JF - Biomaterials

IS - 18

ER -

PH-dependent, thermosensitive polymeric nanocarriers for drug delivery to solid tumors

Abstract

Keywords

ASJC Scopus subject areas

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