A Serum-Stable supramolecular drug carrier for chemotherapeutics fabricated by a Peptide-Photosensitizer conjugate

Jincan Chen; Yang Zhou; Meiru Song; Yijian Chen; Dong Wang; Yunmei Huang; Ping Hu; Chen He; Tao Dai; Lei Zhang; Mingdong Huang; Zhuo Chen; Peng Xu

doi:10.1016/j.jcis.2023.05.131

A Serum-Stable supramolecular drug carrier for chemotherapeutics fabricated by a Peptide-Photosensitizer conjugate

J Colloid Interface Sci. 2023 Sep 15:646:959-969. doi: 10.1016/j.jcis.2023.05.131. Epub 2023 May 20.

Authors

Jincan Chen¹, Yang Zhou², Meiru Song², Yijian Chen³, Dong Wang¹, Yunmei Huang⁴, Ping Hu³, Chen He¹, Tao Dai¹, Lei Zhang¹, Mingdong Huang², Zhuo Chen⁵, Peng Xu⁶

Affiliations

¹ State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fujian College, University of Chinese Academy of Sciences, Fuzhou, Fujian 350002, China; University of Chinese Academy of Sciences, Beijing 100049, China.
² College of Chemistry, Fuzhou University, Fuzhou, Fujian 350116, China.
³ State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fujian College, University of Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.
⁴ Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.
⁵ State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fujian College, University of Chinese Academy of Sciences, Fuzhou, Fujian 350002, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: zchen@fjirsm.ac.cn.
⁶ College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350116, China. Electronic address: pengxu@fzu.edu.cn.

PMID: 37235941
DOI: 10.1016/j.jcis.2023.05.131

Abstract

Supramolecular assemblies fabricated by peptide-photosensitizer conjugates have attracted increasing attentions in recent years as drug carriers for chemotherapeutics (CTs). However, these assemblies have been known to suffer from disintegration by serum components leading to off-target drug release, and thereby impairing antitumor effects and causing systemic toxicities. To address this problem, this study reports a nano-architectural self-assembly peptide-photosensitizer carrier (NSPC) fabricated by conjugating a phthalocyanine derivative (MCPZnPc) and ε-poly-l-lysine (EPL). By engineering the core and peripheral interactions, MCPZnPC-EPL (M-E) NSPC firmly encapsulated multiple CTs, creating CT@M-E NSPCs that were highly stable against disintegration in serum. More importantly, CT@M-E NSPCs exhibited controlled release of CTs in tumor tissues. The antitumor effects of CTs were further promoted by the synergism with the reactivated photodynamic effect. Furthermore, M-E NSPC-encapsulation optimized CTs' biodistribution reducing adverse effects in vivo. This study provides a serum-stable supramolecular drug delivery system with photodynamic effect, which is applicable for a broad-range of CTs to promote antitumor effects and ameliorate adverse effects.

Keywords: Chemotherapeutics; Drug delivery system; Peptide-photosensitizer conjugate; Serum stability; Supramolecular assemblies.

MeSH terms

Cell Line, Tumor
Drug Carriers
Drug Delivery Systems
Drug Liberation
Peptides / pharmacology
Photochemotherapy*
Photosensitizing Agents* / pharmacology
Photosensitizing Agents* / therapeutic use
Tissue Distribution

Substances

Photosensitizing Agents
Drug Carriers
Peptides