title: Quantitative analysis of dendron-conjugated cisplatin-complexed gold nanoparticles using scanning particle mobility mass spectrometry.
abstract: We report a high-resolution and traceable method to quantify the drug loading on nanoparticle-based cancer therapeutics, and demonstrate this method using a model cisplatin functionalized dendron-gold nanoparticle (AuNP) conjugate. Electrospray differential mobility analysis (ES-DMA) provides upstream size classification based on the electrical mobility of AuNP conjugates in aerosol form following electrospray conversion from the aqueous suspension. A condensation particle counter (CPC) and inductively coupled plasma mass spectrometer (ICP-MS) provide the principal downstream quantification. CPC and ICP-MS yield complementary number-based and elemental mass-based particle size distributions, respectively. Conjugation using three different dendron formulations was differentiated based on changes in the mean mobility particle size. The subsequent cisplatin complexation to the dendron conjugates was quantified by coupling ES-DMA with ICP-MS. Discrete AuNP clusters (e.g., dimers, trimers) could be resolved from the relative quantity of atoms (i.e., Au and Pt) per particle after separation by ES-DMA. Surface density of cisplatin on Au was shown to be proportional to the density of carboxylic groups present and was independent of the state of AuNP clustering. Additionally, we found that colloidal stability of the conjugate is inversely proportional to the surface loading of cisplatin. This study demonstrates a prototype methodology to provide traceable quantification and to determine other important formulation factors relevant to therapeutic performance.
authors: Materials Measurement Science Division, National Institute of Standards and Technology, 100 Bureau Drive, Mail Stop 8520, Gaithersburg, MD 20899, USA.
authors: De-Hao
authors: DH
authors: Tsai
authors: Tae Joon
authors: TJ
authors: Cho
authors: Sherrie R
authors: SR
authors: Elzey
authors: Julien C
authors: JC
authors: Gigault
authors: Vincent A
authors: VA
authors: Hackley
mesh_terms: D000873:Anthracenes / Q000737:chemistry*; D002945:Cisplatin / Q000032:analysis*; D006046:Gold / Q000737:chemistry*; D013058:Mass Spectrometry; D053768:Metal Nanoparticles / Q000737:chemistry*; D010316:Particle Size
chemical_list: D000873:Anthracenes; C501244:dendron; D006046:Gold; D002945:Cisplatin