Peidong Wu

1. Developing targeted lipid nanoparticles formulation process and conjugation chemistry for targeting ligands(peptide, small molecules, antibody, vHH) incorporation. 2. Establishing in vitro binding assay for nanoparticles targeting validation and assay automation. 3. Establishing LNP lipid purity analysis and lipid composition analysis with UPLC systems(ELSD, CAD, MS). 4. Establishing targeted nanoparticles conjugation efficiency assay and UPLC methods. 5. Performing cell culture and in vitro transfection assays for LNPs.

Design and prepare small molecule/peptides polymer conjugate for cellular uptake evaluation • Synthesized and characterized biocompatible PEG-PMMA based random and block copolymers by NMR and GPC. • Demonstrated reproducible nanoparticles formulation techniques for drug molecules with different Log P values. • Established nanoparticle characterization methods and protocols: size, drug loading, stimuli-responsive release using various techniques (DLS, UV, HPLC, LC/MS). • Co-decorated cell-targeting ligands and DOTA ligand for quantification of polymeric nanoparticle uptake in a multiplex manner assisted by ICP-MS. • Conveyed a cellular AND gate concept using phosphate terminated self-immolative linker protected sulfonamide decorated nanocarrier, where only under a concurrent exposure of alkaline phosphatase (ALP) and carbonic anhydrase IX (CA IX) would result in enhanced uptake of nanocarrier in CA IX overexpressed cell line. • Designed and prepared small molecule/peptides nanoparticle conjugate for endothelial cell uptake and transcytosis analysis. Design and prepare antibody-nanoparticle conjugate for targeted delivery of therapeutics • Studied the influence of polymer structure and architecture on drug loading and redox-trigger release. • Perform antibody modification using surface lysine to introduce clickable handle (DBCO Azide or TCO Tetrazine) and characterization of linker to antibody ratio by LC-MS. • Synthesis of dibromopyridazinediones for site-specific modification of antibodies via a disulfide rebridging strategy. • Develop and optimize protocols for fabrication of antibody nanogel conjugate and related quality control assays. • Preparation, purification, and characterization of adamantine-containing polymer protein conjugate. • Perform multistep synthesis of Raloxifene-based PROTAC molecules as novel cargos for nanoparticle-assisted delivery. • Demonstrated synthetic routes for CB[7] synthesis, modification, and characterization.

• Perform peptide synthesis using Liberty Blue peptide synthesizer, peptide purification using reverse-phase chromatography (ISCO combiflash and prep-HPLC), and characterization by LC-MS. • Perform small molecule synthesis, purification, and characterization. • Design enzyme activity experiments and optimization of bioconjugation protocol. • Prepare antibody bioconjugation and characterization.