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^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

144 Citations (Scopus)

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. © 2013 Elsevier Ltd.

Original language	English
Pages (from-to)	4501-4509
Journal	Biomaterials
Volume	34
Issue number	18
DOIs	https://doi.org/10.1016/j.biomaterials.2013.02.049
Publication status	Published - Jun 2013
Externally published	Yes

Research Keywords

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

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10.1016/j.biomaterials.2013.02.049

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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. {\textcopyright} 2013 Elsevier Ltd.",

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

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

year = "2013",

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language = "English",

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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.

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. © 2013 Elsevier Ltd.

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. © 2013 Elsevier Ltd.

KW - Anti-cancer

KW - PH-sensitive

KW - Polymeric micelle

KW - Temperature sensitive

KW - Tumor delivery

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U2 - 10.1016/j.biomaterials.2013.02.049

DO - 10.1016/j.biomaterials.2013.02.049

M3 - RGC 21 - Publication in refereed journal

C2 - 23498892

SN - 0142-9612

VL - 34

SP - 4501

EP - 4509

JO - Biomaterials

JF - Biomaterials

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ER -

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

Abstract

Research Keywords

UN SDGs

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