Amino acid-modified PAMAM dendritic nanocarriers as effective chemotherapeutic drug vehicles in cancer treatment: A study using zebrafish as a cancer model

Szu Yuan Wu, Hsiao Ying Chou, Hsieh Chih Tsai*, Rajeshkumar Anbazhagan, Chiou Hwa Yuh, Jen Ming Yang, Yen Hsiang Chang

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

14 Scopus citations

Abstract

The use of nanomaterials for drug delivery offers many advantages including the targeted delivery of drugs and their controlled release. Nonetheless, entry into the target cells remains a challenge for many nanomaterials used for drug delivery. Moreover, cellular uptake limits the therapeutic efficiency of many anticancer drugs. An important goal is to increase the specific accumulation of these nanoparticles (NPs) at the desired cancerous tissues. Notably, cancer cells show a high demand for some amino acids and we have used this knowledge to develop novel carrier systems. In this study, drug carriers were produced by the conjugation of multiple amino acids such asl-histidine (H) andl-cysteine (C) or single amino acids such as only H with the G4.5 dendrimers (G) to produce GHC aggregates and GH NP carriers, respectively. Doxorubicin was loaded into the G4.5, GH, and GHC dendrimers (G/DOX, GH/DOX and GHC/DOX, respectively) and the release mechanism was demonstrated at pH 7.4 and pH 5.0. GH/DOX and GHC/DOX showed better stability under physiological conditions than the dendrimer alone (G/DOX). GH/DOX and GHC/DOX exhibited higher inhibition of HeLa cell proliferation inin vitroandin vivostudies in zebrafish, confirming the early release of DOX by disrupting the endosomal membrane and triggering the destabilization of carriers at a lower pH of 5.0.

Original languageEnglish
Pages (from-to)20682-20690
Number of pages9
JournalRSC Advances
Volume10
Issue number35
DOIs
StatePublished - 01 06 2020

Bibliographical note

Publisher Copyright:
© The Royal Society of Chemistry 2020.

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