Enhanced antitumor and anti-metastasis by VEGFR2-targeted doxorubicin immunoliposome synergy with NK cell activation

Summary Liposomal doxorubicin exhibits stronger drug accumulation at the tumor site due to the Enhanced Permeability and Retention (EPR) effect. However, the prognosis for the patient is poor due to this drug’s lack of targeting and tumor metastasis during treatment. Vascular epidermal growth factor...

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Bibliographic Details
Published in:Investigational new drugs 2023-10, Vol.41 (5), p.664-676
Main Authors: Pan, Mingzhu, Liu, Yali, Sang, Tian, Xie, Jiajun, Lin, Huishu, Wei, Jianpeng, Shao, Shuai, Zheng, Yanying, Zhang, Juan
Format: Article
Language:English
Subjects:
Angiogenesis
Antibodies
Anticancer properties
Antitumor activity
Bispecific antibodies
Cancer
Cell activation
Doxorubicin
Effectiveness
Growth factors
Immune system
Internalization
Medicine
Medicine & Public Health
Metastases
Metastasis
Natural killer cells
Oncology
Permeability
Pharmacology/Toxicology
Polymers
Tumors
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Summary:Summary Liposomal doxorubicin exhibits stronger drug accumulation at the tumor site due to the Enhanced Permeability and Retention (EPR) effect. However, the prognosis for the patient is poor due to this drug’s lack of targeting and tumor metastasis during treatment. Vascular epidermal growth factor receptor (VEGFR2) plays an important role in angiogenesis and cancer metastasis. To enhance antitumor efficacy of PEGylated liposomal doxorubicin, we constructed a VEGFR2-targeted and doxorubicin-loaded immunoliposome (Lipo-DOX-C00) by conjugating a VEGFR2-specific, single chain antibody fragment to DSPE-PEG2000-MAL, and then we inserted the antibody-conjugated polymer into liposomal doxorubicin (Lipo-DOX). The immunoliposome was formed uniformly with high affinity for VEGFR2. In vitro, Lipo-DOX-C00 enhanced doxorubicin internalization into LLC and 4T1 cells compared with non-conjugated, liposomal doxorubicin. In vivo, Lipo-DOX-C00 delivered DOX to tumor tissues effectively, which exhibited an improved antitumor and anti-metastasis efficacy in both LLC subcutaneous tumor models and 4T1 tumor models. In addition, the combined therapy of a VEGFR2–MICA bispecific antibody (JZC01) and Lipo-DOX-C00 achieved enhanced inhibition of cancer growth and metastasis due to activation of the immune system. Our study provides a promising approach to clinical application of liposomal doxorubicin.
ISSN:0167-6997
1573-0646
DOI:10.1007/s10637-023-01372-5