Efficient modification of PAMAM G1 dendrimer surface with β-cyclodextrin units by CuAAC: impact on the water solubility and cytotoxicity

• Published in: RSC advances Vol. 1; no. 43; pp. 25557 - 25566
• Main Authors: Sorroza-Martínez, Kendra, González-Méndez, Israel, Martínez-Serrano, Ricardo D, Solano, José D, Ruiu, Andrea, Illescas, Javier, Zhu, Xiao Xia, Rivera, Ernesto
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 07.07.2020; The Royal Society of Chemistry
• Subjects: Alkynes; Biotechnology; Chemistry; Cycloaddition; Cyclodextrins; Cytotoxicity; Dendrimers; Drug carriers; Mass spectrometry; NMR; Nuclear magnetic resonance; Solubility; Toxicity testing
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d0ra02574g

The toxicity of the poly(amidoamine) dendrimers (PAMAM) caused by the peripheral amino groups has been a limitation for their use as drug carriers in clinical applications. In this work, we completely modified the periphery of PAMAM dendrimer generation 1 (PAMAM G1) with β-cyclodextrin (β-CD) units through the Cu( i )-catalyzed azide-alkyne cycloaddition (CuAAC) to obtain the PAMAM G1-β-CD dendrimer with high yield. The PAMAM G1-β-CD was characterized by 1 H- and 13 C-NMR and mass spectrometry studies. Moreover, the PAMAM G1-β-CD dendrimer showed remarkably higher water solubility than native β-CD. Finally, we studied the toxicity of PAMAM G1-β-CD dendrimer in four different cell lines, human breast cancer cells (MCF-7 and MDA-MB-231), human cervical adenocarcinoma cancer cells (HeLa) and pig kidney epithelial cells (LLC-PK1). The PAMAM G1-β-CD dendrimer did not present any cytotoxicity in cell lines tested which shows the potentiality of this new class of dendrimers. The toxicity of the poly(amidoamine) dendrimers (PAMAM) caused by the peripheral amino groups has been a limitation for their use as drug carriers in clinical applications.