| Autor: |
Saha Ray A; Department of Chemistry and Biochemistry , University of Maryland Baltimore County (UMBC) , Baltimore , Maryland 21250 , United States., Ghann WE; Department of Chemistry and Biochemistry , University of Maryland Baltimore County (UMBC) , Baltimore , Maryland 21250 , United States., Tsoi PS; Department of Chemistry and Biochemistry , University of Maryland Baltimore County (UMBC) , Baltimore , Maryland 21250 , United States., Szychowski B; Department of Chemistry and Biochemistry , University of Maryland Baltimore County (UMBC) , Baltimore , Maryland 21250 , United States., Dockery LT; Department of Chemistry and Biochemistry , University of Maryland Baltimore County (UMBC) , Baltimore , Maryland 21250 , United States., Pak YJ; Department of Pharmaceutical Sciences, Center for Nanobiotechnology , University of Maryland, Baltimore , 20 Penn Street , Baltimore , Maryland 21201 , United States., Li W; Mass Spectrometry Center , University of Maryland School of Pharmacy , Baltimore , Maryland 21201 , United States., Kane MA; Mass Spectrometry Center , University of Maryland School of Pharmacy , Baltimore , Maryland 21201 , United States., Swaan P; Department of Pharmaceutical Sciences, Center for Nanobiotechnology , University of Maryland, Baltimore , 20 Penn Street , Baltimore , Maryland 21201 , United States., Daniel MC; Department of Chemistry and Biochemistry , University of Maryland Baltimore County (UMBC) , Baltimore , Maryland 21250 , United States. |
| Abstrakt: |
The synthesis of a novel poly(propyleneimine) (PPI) dendron in gram scale as well as its use in the formation of a highly stable, dendronized gold nanoparticle (AuNP)-based drug delivery platform is described herein. The AuNP-based platform is composed of three complementary parts: (i) a 15 nm AuNP core, (ii) a heterofunctional thioctic acid-terminated tetraethylene glycol spacer, and (iii) a third-generation PPI dendron with a unique protonation profile and diverse end-group functionalization that allows for further derivatization. The prepared dendronized AuNPs are able to withstand several rounds of lyophilization cycles with no sign of aggregation, are stable in phosphate-buffered saline and Hanks' buffer as well as in serum, and are resistant to degradation by glutathione exchange reactions. This nanocarrier platform displays a dense coating, with >1400 dendrons/AuNPs, which will enable very high payload. Furthermore, while amine-terminated AuNPs expectedly showed cytotoxicity against the MCF-7 breast cancer cell line from a NP concentration of 1 nM, the mixed monolayer AuNPs (coated with 40/60 amine/carboxylate dendrons) interestingly did not exhibit any sign of toxicity at concentrations as high as 15 nM, similar to the carboxylate-terminated AuNPs. The described dendronized AuNPs address the current practical need for a stable NP-based drug delivery platform which is scalable and easily conjugable, has long-term stability in solution, and can be conveniently formulated as a powder and redispersed in desired buffer or serum. |
