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Poly(ethylene Glycol)-Modified PAMAM-Fe3O4-doxorubicin Triads With the Potential for Improved Therapeutic Efficacy: Generation-Dependent Increased Drug Loading and Retention at Neutral pH and Increased Release at Acidic pH

Poly(ethylene Glycol)-Modified PAMAM-Fe3O4-doxorubicin Triads With the Potential for Improved Therapeutic Efficacy: Generation-Dependent Increased Drug Loading and Retention at Neutral pH and Increased Release at Acidic pH

Saumya Nigam, Sudeshna Chandra, Donald F Newgreen, Dhirendra Bahadur, Qizhi Chen

Langmuir. 2014 Feb 4;30(4):1004-11.

PMID: 24446987

Abstract:

Polyamidoamine (PAMAM) dendrimer-coated magnetic nanoparticles are a promising drug-delivery system that can enhance the therapeutic effects of chemotherapy drugs, such as doxorubicin (DOX), with minimized side effects. This work explores the optimization of the potential therapeutic efficiency of PAMAM-Fe3O4-DOX triads. Different generations (G3, G5, and G6) of PAMAMs were synthesized and modified with poly(ethylene glycol) (PEG) and then used to encapsulate glutamic acid-modified Fe3O4 nanoparticles. The Fe3O4-dendrimer carriers (Fe3O4-DGx where x = the generation 3, 5, or 6 of dendrimers) were electrostatically conjugated with drug DOX. The loading and releasing efficiencies of DOX increased with the PAMAM generation from 3 to 6. The loading efficiencies of DOX molecules were 87, 93, and 96% for generations 3, 5, and 6, respectively. At pH 5, the DOX release efficiencies within 24 h were approximately 60, 68, and 80% for generations 3, 5, and 6, respectively. At pH 7.4, the DOX releasing efficiency was as low as ∼ 15%. Compared to the negative control, the PAMAM-Fe3O4-DOX triads showed only mild toxicity against human cervical adenocarcinoma cell line HeLa at pH 7.4, which indicated that DOX can be fairly benignly carried and sparingly released until PAMAM-Fe3O4-DOX is taken up into the cell.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP313691804	Thiophosphoryl-PMMH-24 dendrimer, generation 3.5		313691-80-4	Price
LS762100	PAMAM-OH dendrimer, generation 6 solution			Price

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