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 Ivrine, Meng Zhang, Xinhua Liu, Yiqing Lu, Bingyang Shi

Research output: Contribution to journalArticlepeer-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.
Original languageEnglish
Pages (from-to)2148-2158
Number of pages11
JournalBiomacromolecules
Volume20
Issue number5
DOIs
Publication statusPublished - 17 Apr 2019

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