Set of Highly Stable Amine- and Carboxylate-Terminated Dendronized Au Nanoparticles with Dense Coating and Nontoxic Mixed-Dendronized Form.

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.

Syntheses and characterization of lisinopril-coated gold nanoparticles as highly stable targeted CT contrast agents in cardiovascular diseases.

Lisinopril was used as the targeting moiety to prepare gold nanoparticle-based functional CT contrast agents. Pure lisinopril, thioctic acid-lisinopril conjugate, and reduced thioctic acid-lisinopril conjugate were used to obtain GNP-Lis, GNP-TA-Lis, and GNP-RTA-Lis, respectively, via ligand exchange reaction on citrate-coated gold nanoparticles (GNPs). These lisinopril-decorated GNPs were fully characterized, and their chemical stabilities in biological relevant media and in high salt concentration were compared. Their relative stabilities toward lyophilization and against cyanide-induced decomposition were also investigated. Because of their higher stability, GNP-TA-Lis were used to assess the targeting of angiotensin converting enzyme (ACE) using X-ray computed tomography (CT). The images obtained displayed high contrast in the region of the lungs and heart, clearly indicating the targeting of ACE, whose overexpression is associated with development of cardiac and pulmonary fibrosis. Thus, the new nanoprobes prepared here will serve as very useful tools for the monitoring of cardiovascular pathophysiologies using CT imaging.