Label-free fluorescent poly(amidoamine) dendrimer for traceable and controlled drug delivery

Guoying Wang, Libing Fu, Adam Walker, Xianfeng Chen, David B. Lovejoy, Mingcong Hao, Albert Lee, Roger Chung, Helen Rizos, Mal Irvine, Meng Zheng, Xiuhua Liu, Yiqing Lu, Bingyang Shi

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Poly(amidoamine) dendrimer (PAMAM) is well-known for its high efficiency as a drug delivery vehicle. However, the intrinsic cytotoxicity and lack of a detectable signal to facilitate tracking have impeded its practical applications. Herein, we have developed a novel label-free fluorescent and biocompatible PAMAM derivative by simple surface modification of PAMAM using acetaldehyde. The modified PAMAM possessed a strong green fluorescence, which was generated by the C=N bonds of the resulting Schiff Bases via n−π* transition, while the intrinsic cytotoxicity of PAMAM was simultaneously ameliorated. Through further PEGylation, the fluorescent PAMAM demonstrated excellent intracellular tracking in human melanoma SKMEL28 cells. In addition, our PEGylated fluorescent PAMAM derivative achieved enhanced loading and delivery efficiency of the anticancer drug doxorubicin (DOX) compared to the original PAMAM. Importantly, the accelerated kinetics of DOX-encapsulated fluorescent PAMAM nanocomposites in an acidic environment facilitated intracellular drug release, which demonstrated comparable cytotoxicity to that of the free-form doxorubicin hydrochloride (DOX·HCl) against melanoma cells. Overall, our label free fluorescent PAMAM derivative offers a new opportunity of traceable and controlled delivery for DOX and other drugs of potential clinical importance.
LanguageEnglish
Pages2148-2158
Number of pages11
JournalBiomacromolecules
Volume20
Issue number5
Early online date17 Apr 2019
DOIs
Publication statusPublished - 13 May 2019

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Controlled drug delivery
Dendrimers
Cytotoxicity
Doxorubicin
Labels
Derivatives
Acetaldehyde
Pharmaceutical Preparations
Drug delivery
Surface treatment
Schiff Bases
Nanocomposites
Fluorescence
Kinetics
Poly(amidoamine)

Cite this

@article{3a1fa53f36184286837374cf1069d577,
title = "Label-free fluorescent poly(amidoamine) dendrimer for traceable and controlled drug delivery",
abstract = "Poly(amidoamine) dendrimer (PAMAM) is well-known for its high efficiency as a drug delivery vehicle. However, the intrinsic cytotoxicity and lack of a detectable signal to facilitate tracking have impeded its practical applications. Herein, we have developed a novel label-free fluorescent and biocompatible PAMAM derivative by simple surface modification of PAMAM using acetaldehyde. The modified PAMAM possessed a strong green fluorescence, which was generated by the C=N bonds of the resulting Schiff Bases via n−π* transition, while the intrinsic cytotoxicity of PAMAM was simultaneously ameliorated. Through further PEGylation, the fluorescent PAMAM demonstrated excellent intracellular tracking in human melanoma SKMEL28 cells. In addition, our PEGylated fluorescent PAMAM derivative achieved enhanced loading and delivery efficiency of the anticancer drug doxorubicin (DOX) compared to the original PAMAM. Importantly, the accelerated kinetics of DOX-encapsulated fluorescent PAMAM nanocomposites in an acidic environment facilitated intracellular drug release, which demonstrated comparable cytotoxicity to that of the free-form doxorubicin hydrochloride (DOX·HCl) against melanoma cells. Overall, our label free fluorescent PAMAM derivative offers a new opportunity of traceable and controlled delivery for DOX and other drugs of potential clinical importance.",
author = "Guoying Wang and Libing Fu and Adam Walker and Xianfeng Chen and Lovejoy, {David B.} and Mingcong Hao and Albert Lee and Roger Chung and Helen Rizos and Mal Irvine and Meng Zheng and Xiuhua Liu and Yiqing Lu and Bingyang Shi",
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month = "5",
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Label-free fluorescent poly(amidoamine) dendrimer for traceable and controlled drug delivery. / Wang, Guoying; Fu, Libing; Walker, Adam; Chen, Xianfeng; Lovejoy, David B.; Hao, Mingcong; Lee, Albert; Chung, Roger; Rizos, Helen; Irvine, Mal; Zheng, Meng; Liu, Xiuhua; Lu, Yiqing; Shi, Bingyang.

In: Biomacromolecules, Vol. 20, No. 5, 13.05.2019, p. 2148-2158.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Label-free fluorescent poly(amidoamine) dendrimer for traceable and controlled drug delivery

AU - Wang,Guoying

AU - Fu,Libing

AU - Walker,Adam

AU - Chen,Xianfeng

AU - Lovejoy,David B.

AU - Hao,Mingcong

AU - Lee,Albert

AU - Chung,Roger

AU - Rizos,Helen

AU - Irvine,Mal

AU - Zheng,Meng

AU - Liu,Xiuhua

AU - Lu,Yiqing

AU - Shi,Bingyang

PY - 2019/5/13

Y1 - 2019/5/13

N2 - Poly(amidoamine) dendrimer (PAMAM) is well-known for its high efficiency as a drug delivery vehicle. However, the intrinsic cytotoxicity and lack of a detectable signal to facilitate tracking have impeded its practical applications. Herein, we have developed a novel label-free fluorescent and biocompatible PAMAM derivative by simple surface modification of PAMAM using acetaldehyde. The modified PAMAM possessed a strong green fluorescence, which was generated by the C=N bonds of the resulting Schiff Bases via n−π* transition, while the intrinsic cytotoxicity of PAMAM was simultaneously ameliorated. Through further PEGylation, the fluorescent PAMAM demonstrated excellent intracellular tracking in human melanoma SKMEL28 cells. In addition, our PEGylated fluorescent PAMAM derivative achieved enhanced loading and delivery efficiency of the anticancer drug doxorubicin (DOX) compared to the original PAMAM. Importantly, the accelerated kinetics of DOX-encapsulated fluorescent PAMAM nanocomposites in an acidic environment facilitated intracellular drug release, which demonstrated comparable cytotoxicity to that of the free-form doxorubicin hydrochloride (DOX·HCl) against melanoma cells. Overall, our label free fluorescent PAMAM derivative offers a new opportunity of traceable and controlled delivery for DOX and other drugs of potential clinical importance.

AB - Poly(amidoamine) dendrimer (PAMAM) is well-known for its high efficiency as a drug delivery vehicle. However, the intrinsic cytotoxicity and lack of a detectable signal to facilitate tracking have impeded its practical applications. Herein, we have developed a novel label-free fluorescent and biocompatible PAMAM derivative by simple surface modification of PAMAM using acetaldehyde. The modified PAMAM possessed a strong green fluorescence, which was generated by the C=N bonds of the resulting Schiff Bases via n−π* transition, while the intrinsic cytotoxicity of PAMAM was simultaneously ameliorated. Through further PEGylation, the fluorescent PAMAM demonstrated excellent intracellular tracking in human melanoma SKMEL28 cells. In addition, our PEGylated fluorescent PAMAM derivative achieved enhanced loading and delivery efficiency of the anticancer drug doxorubicin (DOX) compared to the original PAMAM. Importantly, the accelerated kinetics of DOX-encapsulated fluorescent PAMAM nanocomposites in an acidic environment facilitated intracellular drug release, which demonstrated comparable cytotoxicity to that of the free-form doxorubicin hydrochloride (DOX·HCl) against melanoma cells. Overall, our label free fluorescent PAMAM derivative offers a new opportunity of traceable and controlled delivery for DOX and other drugs of potential clinical importance.

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