Targeted delivery of anticancer agents via a dual function nanocarrier with an interfacial drug-interactive motif

Xiaolan Zhang; Yixian Huang; Wenchen Zhao; Hao Liu; Rebecca Marquez; Jianqin Lu; Peng Zhang; Yifei Zhang; Jiang Li; Xiang Gao; Raman Venkataramanan; Liang Xu; Song Li

doi:10.1021/bm501339j

Targeted delivery of anticancer agents via a dual function nanocarrier with an interfacial drug-interactive motif

Xiaolan Zhang
, Yixian Huang
, Wenchen Zhao
, Hao Liu
, Rebecca Marquez
, Jianqin Lu
, Peng Zhang
, Yifei Zhang
, Jiang Li
, Xiang Gao
, Raman Venkataramanan
, Liang Xu
, Song Li

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

21 Scopus citations

Abstract

We have developed a dual-function drug carrier, polyethylene glycol (PEG)-derivatized farnesylthiosalicylate (FTS). Here we report that incorporation of a drug-interactive motif (Fmoc) into PEG_5k-FTS₂ led to further improvement in both drug loading capacity and formulation stability. Doxorubicin (DOX) formulated in PEG_5k-Fmoc-FTS₂ showed sustained release kinetics slower than those of DOX loaded in PEG_5k-FTS₂. The maximum tolerated dose of DOX- or paclitaxel (PTX)-loaded PEG_5k-Fmoc-FTS₂ was significantly higher than that of the free drug. Pharmacokinetics and biodistribution studies showed that DOX/PEG_5k-Fmoc-FTS₂ mixed micelles were able to retain DOX in the bloodstream for a significant amount of time and efficiently deliver the drug to tumor sites. More importantly, drug (DOX or PTX)-loaded PEG_5k-Fmoc-FTS₂ led to superior antitumor activity over other treatments including drugs formulated in PEG_5k-FTS₂ in breast cancer and prostate cancer models. Our improved dual function carrier with a built-in drug-interactive motif represents a simple and effective system for targeted delivery of anticancer agents.

Original language	English (US)
Pages (from-to)	4326-4335
Number of pages	10
Journal	Biomacromolecules
Volume	15
Issue number	11
DOIs	https://doi.org/10.1021/bm501339j
State	Published - Oct 17 2014
Externally published	Yes

ASJC Scopus subject areas

Bioengineering
Biomaterials
Polymers and Plastics
Materials Chemistry

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10.1021/bm501339j

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title = "Targeted delivery of anticancer agents via a dual function nanocarrier with an interfacial drug-interactive motif",

abstract = "We have developed a dual-function drug carrier, polyethylene glycol (PEG)-derivatized farnesylthiosalicylate (FTS). Here we report that incorporation of a drug-interactive motif (Fmoc) into PEG5k-FTS2 led to further improvement in both drug loading capacity and formulation stability. Doxorubicin (DOX) formulated in PEG5k-Fmoc-FTS2 showed sustained release kinetics slower than those of DOX loaded in PEG5k-FTS2. The maximum tolerated dose of DOX- or paclitaxel (PTX)-loaded PEG5k-Fmoc-FTS2 was significantly higher than that of the free drug. Pharmacokinetics and biodistribution studies showed that DOX/PEG5k-Fmoc-FTS2 mixed micelles were able to retain DOX in the bloodstream for a significant amount of time and efficiently deliver the drug to tumor sites. More importantly, drug (DOX or PTX)-loaded PEG5k-Fmoc-FTS2 led to superior antitumor activity over other treatments including drugs formulated in PEG5k-FTS2 in breast cancer and prostate cancer models. Our improved dual function carrier with a built-in drug-interactive motif represents a simple and effective system for targeted delivery of anticancer agents.",

author = "Xiaolan Zhang and Yixian Huang and Wenchen Zhao and Hao Liu and Rebecca Marquez and Jianqin Lu and Peng Zhang and Yifei Zhang and Jiang Li and Xiang Gao and Raman Venkataramanan and Liang Xu and Song Li",

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AU - Zhang, Xiaolan

AU - Huang, Yixian

AU - Zhao, Wenchen

AU - Liu, Hao

AU - Marquez, Rebecca

AU - Lu, Jianqin

AU - Zhang, Peng

AU - Zhang, Yifei

AU - Li, Jiang

AU - Gao, Xiang

AU - Venkataramanan, Raman

AU - Xu, Liang

AU - Li, Song

PY - 2014/10/17

Y1 - 2014/10/17

N2 - We have developed a dual-function drug carrier, polyethylene glycol (PEG)-derivatized farnesylthiosalicylate (FTS). Here we report that incorporation of a drug-interactive motif (Fmoc) into PEG5k-FTS2 led to further improvement in both drug loading capacity and formulation stability. Doxorubicin (DOX) formulated in PEG5k-Fmoc-FTS2 showed sustained release kinetics slower than those of DOX loaded in PEG5k-FTS2. The maximum tolerated dose of DOX- or paclitaxel (PTX)-loaded PEG5k-Fmoc-FTS2 was significantly higher than that of the free drug. Pharmacokinetics and biodistribution studies showed that DOX/PEG5k-Fmoc-FTS2 mixed micelles were able to retain DOX in the bloodstream for a significant amount of time and efficiently deliver the drug to tumor sites. More importantly, drug (DOX or PTX)-loaded PEG5k-Fmoc-FTS2 led to superior antitumor activity over other treatments including drugs formulated in PEG5k-FTS2 in breast cancer and prostate cancer models. Our improved dual function carrier with a built-in drug-interactive motif represents a simple and effective system for targeted delivery of anticancer agents.

AB - We have developed a dual-function drug carrier, polyethylene glycol (PEG)-derivatized farnesylthiosalicylate (FTS). Here we report that incorporation of a drug-interactive motif (Fmoc) into PEG5k-FTS2 led to further improvement in both drug loading capacity and formulation stability. Doxorubicin (DOX) formulated in PEG5k-Fmoc-FTS2 showed sustained release kinetics slower than those of DOX loaded in PEG5k-FTS2. The maximum tolerated dose of DOX- or paclitaxel (PTX)-loaded PEG5k-Fmoc-FTS2 was significantly higher than that of the free drug. Pharmacokinetics and biodistribution studies showed that DOX/PEG5k-Fmoc-FTS2 mixed micelles were able to retain DOX in the bloodstream for a significant amount of time and efficiently deliver the drug to tumor sites. More importantly, drug (DOX or PTX)-loaded PEG5k-Fmoc-FTS2 led to superior antitumor activity over other treatments including drugs formulated in PEG5k-FTS2 in breast cancer and prostate cancer models. Our improved dual function carrier with a built-in drug-interactive motif represents a simple and effective system for targeted delivery of anticancer agents.

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Targeted delivery of anticancer agents via a dual function nanocarrier with an interfacial drug-interactive motif

Abstract

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