Tumor-targeting photodynamic therapy based on folate-modified polydopamine nanoparticles

Abstract

Shufeng Yan,1 Qingqing Huang,1 Jincan Chen,2 Xiaorong Song,2 Zhuo Chen,2 Mingdong Huang,3 Peng Xu,4 Juncheng Zhang11Medical Plant Exploitation and Utilization Engineering Research Center, Sanming University, Sanming, Fujian 365004, People’s Republic of China; 2State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, People’s Republic of China; 3College of Chemistry, Fuzhou University, Fuzhou, Fujian 350116, People’s Republic of China; 4Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Singapore 138673, SingaporeCorrespondence: Peng XuInstitute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), 61 Biopolis Dr, Singapore 138673, SingaporeEmail [email protected] ZhangMedical Plant Exploitation and Utilization Engineering Research Center, Sanming University, 25 Jingdong Road, Sanming, Fujian 365004, People’s Republic of ChinaEmail [email protected]: Photodynamic therapy (PDT), a clinical anticancer therapeutic modality, has a long history in clinical cancer treatments since the 1970s. However, PDT has not been widely used largely because of metabolic problems and off-target phototoxicities of the current clinical photosensitizers.Purpose: The objective of the study is to develop a high-efficiency and high-specificity carrier to precisely deliver photosensitizers to tumor sites, aiming at addressing metabolic problems, as well as the systemic damages current clinical photosensitizers are known to cause.Methods: We synthesized a polydopamine (PDA)-based carrier with the modification of folic acid (FA), which is to target the overexpressed folate receptors on tumor surfaces. We used this carrier to load a cationic phthalocyanine-type photosensitizer (Pc) and generated a PDA-FA-Pc nanomedicine. We determined the antitumor effects and the specificity to tumor cell lines in vitro. In addition, we established human cancer-xenografted mice models to evaluate the tumor-targeting property and anticancer efficacies in vivo.Results: Our PDA-FA-Pc nanomedicine demonstrated a high stability in normal physiological conditions, however, could specifically release photosensitizers in acidic conditions, eg, tumor microenvironment and lysosomes in cancer cells. Additionally, PDA-FA-Pc nanomedicine demonstrated a much higher cellular uptake and phototoxicity in cancer cell lines than in healthy cell lines. Moreover, the in vivo imaging data indicated excellent tumor-targeting properties of PDA-FA-Pc nanomedicine in human cancer-xenografted mice. Lastly, PDA-FA-Pc nanomedicine was found to significantly suppress tumor growth within two human cancer-xenografted mice models.Conclusion: Our current study not only demonstrates PDA-FA-Pc nanomedicine as a highly potent and specific anticancer agent, but also suggests a strategy to address the metabolic and specificity problems of clinical photosensitizers.Keywords: tumor-targeting, photodynamic therapy, folate receptors, polydopamine nanoparticles, anticancer specificity

Keywords

• Tumor-targeting
• Photodynamic therapy
• Folate receptors
• Polydopamine nanoparticles
• Anticancer specificity