Dual-Ligand Synergistic Targeting Anti-Tumor Nanoplatforms with Cascade-Responsive Drug Release

Author:

Luo Fang12,Zhong Ting12,Chen Ying13,Guo Qianqian13,Tao Ling13,Shen Xiangchun13ORCID,Fan Yanhua12,Wu Xingjie13ORCID

Affiliation:

1. State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, China

2. The Key Laboratory of Chemistry for Natural Products of Guizhou Province, Chinese Academy of Sciences, Guiyang 550014, China

3. The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province (The Key Laboratory of Optimal Utilization of Natural Medicine Resources), School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, China

Abstract

Dual-ligand targeting drug delivery nanoplatforms are considered a promising tool for enhancing the specificity of chemotherapy. However, serious off-target delivery has been observed in current dual-ligand targeting nanoplatforms, as each ligand can independently recognize receptors on the cell membrane surface and guide drug nanocarriers to different cells. To overcome this barrier, a dual-ligand synergistic targeting (DLST) nanoplatform is developed, which can guide chemotherapy treatment specifically to cancer cells simultaneously overexpressing two receptors. This nanoplatform consists of a singlet oxygen (1O2) photosensitizer-loaded nanocarrier and a drug-loaded nanocarrier with 1O2 responsiveness, which were, respectively, decorated with a pair of complementary DNA sequences and two different ligands. For cancer cells overexpressing both receptors, two nanocarriers can be internalized in larger quantities to cause DNA hybridization-induced nanocarrier aggregation, which further activates 1O2-triggered drug release under light irradiation. For cells overexpressing a single receptor, only one type of nanocarrier can be internalized in a large quantity, leading to blocked drug release due to the ultrashort action radius of 1O2. In vivo evaluation showed this DLST nanoplatform displayed highly specific tumor treatment with minimized long-term toxicity. This is a highly efficient drug delivery system for DLST chemotherapy, holding great potential for clinical applications.

Funder

National Natural Science Foundation of China

Guizhou Provincial Department of Education

Thousands of Innovative Talents of Guizhou Province

Publisher

MDPI AG

Subject

Pharmaceutical Science

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