THESIS: Snežana Đorđević

24may11:3013:30THESIS: Snežana ĐorđevićDevelopment of analytical procedures for the characterization of polypeptide-based nanoconjugates

Event Details

Thesis Title: Development of analytical procedures for the characterization of polypeptide-based nanoconjugates

Author: Snežana Đorđević

Supervisor: Prof. María J. Vicent

Tutor: Prof. Ramon Martínez-Máñez


Due to the (poly)ionic and proteinic nature of polypeptide-drug conjugates (PDCs), their translation “from bench to bedside” represents a complex and expensive undertaking, requiring reproducible and scalable polymerization techniques, the implementation of sophisticated analytical tools, exhaustive characterization steps, and the collection of detailed safety and efficacy data.

Classical techniques, such as liquid chromatography (LC) – UV/Vis and size exclusion chromatography (SEC) implemented in the quality control of PDCs during and after synthesis, cannot always support a qualitative and quantitative analysis of degradation products and metabolites. As an alternative, mass spectrometry (MS) and asymmetric flow field flow fractionation (AF4) have grown in influence on polypeptide and PDC characterization. The analysis of drug and degradation products/metabolites can take advantage of LC when coupled to MS. Meanwhile, AF4-mediated separation does not suffer from problems related to the interaction of the analyte with the column like in SEC; instead, AF4 applies a cross flow in an empty channel, which supports the “tailor-made” separation of molecules according to size and molecular weight.

The research included in this Ph.D. thesis focuses on developing new analytical procedures that will aid the selection of PDC candidates for further preclinical studies. We implemented an artificial intelligence tool (design of experiments) to develop analytical methods and optimize the synthesis of genipin-crosslinked PDCs. Moreover, we explored relatively new techniques, such as AF4 and mass spectrometry imaging, in developing novel single and combination PDCs and studying their biological fate in the search for efficient therapies for a range of diseases (advanced solid tumors, including triple negative breast, prostate, and pancreatic cancer, as well as spinal cord injury).


(Wednesday) 11:30 - 13:30(GMT+02:00)


Centro de Investigación Príncipe Felipe

Eduardo Primo Yúfera, 3 Valencia Spain