An Alternating Irradiation Strategy‐Driven Combination Therapy of PDT and RNAi for Highly Efficient Inhibition of Tumor Growth and Metastasis. Issue 8 (13th December 2020)

• Record Type: Journal Article
• Authors: Yue, Dong; Cai, Xiaojun; Fan, Mengni; Zhu, Jingwu; Tian, Jiang; Wu, Lihuang; Jiang, Qian; Gu, Zhongwei
• Is Part Of: Advanced healthcare materials. Volume 10:Issue 8(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-13
• Subjects: hypoxia -- light dose -- photodynamic therapy -- RNA interference -- tumor metastases; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.202001850
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract: Hypoxia and hypoxia induced overexpression of vascular endothelial growth factor (VEGF) not only seriously affects the treatment effects of photodynamic therapy (PDT) but also promotes tumor metastasis. Herein, an alternating irradiation strategy (referred to as alternate use of low/high dose of light [ALH DL ] irradiation)‐driven combination therapy of PDT and RNA interference (RNAi) is developed to synergistically inhibit tumor growth and metastasis. A cationic amphipathic peptide (ALS) served as a carrier in the co‐delivery system of photochlor (HPPH) and siVEGF (ALSH/siVEGF). At the beginning of ALH DL ‐driven ALSH/siVEGF treatment, short‐term LDL irradiation can facilitate the tumor penetration, cellular uptake, and endosome escape of ALSH/siVEGF. Moreover, accompanied by HDL‐mediated rapid cell apoptosis and LDL‐mediated efficient VEGF silencing, the joint use of PDT and RNAi achieved remarkable antitumor effects both in vitro and in vivo. Importantly, benefited from the excellent performance of ALH DL in slowing the rapid deterioration of the anoxic environment of tumors, and ALSH/siVEGF treatment‐mediated highly improved VEGF silencing efficacy and inhibitory effect on angiogenesis, the liver and lung metastases of HeLa cells have been successfully suppressed. Together, this study clearly indicates that ALH DL ‐driven combination therapy of PDT and RNAi is a highly effective modality for inhibition of tumor growth and metastasis. Abstract : An alternating irradiation strategy (referred to as the alternate use of low/high dose of light irradiation, ALH DL )‐driven combination therapy of photodynamic therapy and siVEGF is proposed to synergistic inhibit of tumor growth and metastasis via the HDL‐mediated rapid apoptosis of the superficial tumor cells, as well as the LDL‐mediated efficient vascular endothelial growth factor (VEGF) silencing within the deep‐seated tumor cells.