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Abstract
Background
Existing therapeutic efficacy of chemotherapy and photodynamic therapy (PDT) is always affected by some resistance factors from tumour environment (TME), such as hypoxia and the antioxidant defense system.
Purpose
This study aims at developing a cascaded intelligent multifunctional nanoplatforms to modulate the TME resistance for synergistically enhanced chemo- and photodynamic therapies.
Methods
In this study, we synthesised hollow manganese dioxide nanoparticles (HMDNs) loaded with the hydrophilic chemotherapeutic drug (acriflavine, ACF) and the hydrophobic photosensitizer (chlorine6, Ce6), which was further encapsulated by pH-sensitive liposome to form core-shell nanocomposite, with surface modified with arginine-glycine-aspartic acid (RGD) peptide to achieve tumour targeting.
Results
After uptake by tumour cells, the liposome shell was rapidly degraded by the low pH, and the inner core could be released from the liposome. Then, the released HMDNs/ACF/Ce6 would be dissociated by low pH and high levels of intracellular GSH within TME to release encapsulated drugs, thereby resulting in synergistic effects of chemotherapy and PDT. Meanwhile, the released ACF could bind with HIF-1a and then inhibit the expression levels of HIF-1’s downstream signalling molecules P-gp and VEGF, which could further strengthen the antitumor effects. As a result, HMDNs/ACF/Ce6@Lipo-RGD NPs with laser irradiation exhibited superior anti-tumour therapeutic efficiency.
Ethics approval
The protocol of animal experiments was approved by the Ethics Committee of Hebei Medical University, and all experimental procedures followed the Provisions and General Recommendation of Chinese Experimental Animals Administration Legislation. All animal procedures follow the criteria of the National Regulation on the Management of Laboratory Animals and the protocol was approved by the Committee on the Ethics of Animal Experiments of Hebei Medical University.
Author contributions
Xiangtian Deng wrote the manuscript. Qingcheng Song and Yiran Zhang were responsible for language modification and correction. Professor Weijian Liu, Professor Hongzhi Hu, and Professor Yingze Zhang illuminated instruction and expert advice for this paper. All authors read and approved the final manuscript.
Disclosure statement
The authors report no conflicts of interest in this work.
Data availability statement
The datasets supporting the conclusions of this article are included within the article and its supplementary file.