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Enhanced Biocompatibility of PAMAM Dendrimers Benefiting From Tuning Their Surface Charges

Enhanced Biocompatibility of PAMAM Dendrimers Benefiting From Tuning Their Surface Charges

Yanshuai Cui, Bo Liang, Longgang Wang, Linlin Zhu, Jianxin Kang, Haotian Sun, Shengfu Chen

Mater Sci Eng C Mater Biol Appl. 2018 Dec 1;93:332-340.

PMID: 30274065

Abstract:

The surface charge of dendrimers is one of the key factors that determine their use in nanomedicine. Generation 5 poly(amido amine) dendrimers (G5 PAMAM) encapsulating with fluorescein sodium were employed to study the method to tune surface charge. Firstly, the surface primary amines were reacted with maleic anhydride to introduce double bonds. Then, l-cysteine and cysteamine were conjugated to these double bonds via thiol-ene additions in water, respectively. The surface charges of modified G5 PAMAMs were successfully controlled by tuning the molar ratio of L-cysteine to cysteamine. The surface charges of the resulting modified G5 PAMAMs varied from -16.0 mV to -3.7 mV at physiological pH. In addition, they showed good compatibility with proteins and cells compared with G5 PAMAM. Modified G5 PAMAMs and fibrinogen could coexist in solution without generating noticeable aggregation, while G5 PAMAM induces significant aggregation, indicating these modifications can effectively reduce the interaction force between G5 PAMAM and proteins. Furthermore, modified G5 PAMAMs exhibited negligible hemolysis, while G5 PAMAM caused severe hemolysis. The cytotoxicity assay demonstrated that modified G5 PAMAMs exhibited very low cytotoxicity to both HUVEC cells and KB cells (>90% cell viability) at high concentrations up to 2 mg/mL. The cellular uptake of them was much less efficient compared with that of G5 PAMAM. Moreover, the intravenous injected modified G5 PAMAMs were excreted by kidney with a relatively little accumulation in liver, confirming their good biocompatibility in vivo. It is expected that the modified G5 PAMAMs could be an excellent candidate for contrast agent carriers in the future.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
LS76299	PAMAM-OH dendrimer, generation 5 solution			Price

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