Tumor-targeting photodynamic therapy based on folate-modified polydopamine nanoparticles
Received 18 May 2019
Accepted for publication 27 July 2019
Published 23 August 2019 Volume 2019:14 Pages 6799—6812
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 5
Editor who approved publication: Prof. Dr. Anderson Oliveira Lobo
Shufeng Yan,1 Qingqing Huang,1 Jincan Chen,2 Xiaorong Song,2 Zhuo Chen,2 Mingdong Huang,3 Peng Xu,4 Juncheng Zhang1
1Medical 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, Singapore
Correspondence: Peng Xu
Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), 61 Biopolis Dr, Singapore 138673, Singapore
Medical Plant Exploitation and Utilization Engineering Research Center, Sanming University, 25 Jingdong Road, Sanming, Fujian 365004, People’s Republic of China
Background: 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
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