Anti-cancer drug containing apolipoprotein B refolding through first-order-like phase transition process

Chia Hsin Cheng^1*, Wei-Ping Chang¹, Po-Yen Lin², Yu Chuan Liang³, Caleb G. Chen⁴, Chia-Ching Chang^1,5

¹Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan
²Division of Core Facilities Imaging, Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
³Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan
⁴Department of Hematology-Oncology, Mackay Memorial Hospital, Taipei, Taiwan
⁵Institute of Physics, Academia Sinica, Taipei, Taiwan

* Presenter:Chia Hsin Cheng, email:chris32041@gmail.com

Corresponding author: Chia-Ching Chang (ccchang01@faculty.nctu.edu.tw)

First-order-like phase transition process is a promising approach for protein refolding into its functional state. However, lipid binding protein, apolipoprotein B (apoB), reconstitution is challenging until our previous study. In this study, we refolded apoB with anti-cancer drug from denatured state to functional state follow a first-order-like state transition model. The apoB is the ligand of LDL receptor (LDLR). There are many cancer cells which overexpress LDLRs on their surface.Therefore, the reconstituted apoB lipoparticle (rABL) will be an idea vehicle for hydrophobic and amphiphilic materials delivery. By characterizing the reconstituted drug loaded rABL (drug@rABL)with circular dichroism(CD), dynamic light scattering (DLS), zeta potential and transmission electron microscope(TEM), we found drug@rABL is similar to rABL and native LDL. Moreover, cell viability assay indicated drug@rABL demonstrated highly anti-cancer efficacy in low concentration. Furthermore, the anti-cancer mechanism of the drug can be revealed, too.

Keywords: First-order-like phase transition process, protein refolding, apolipoprotein B, LDL