![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
Abstract
Numerous nanomedicines have been developed recently that can accumulate selectively in tumours due to the enhanced permeability and retention (EPR) effect. However, the high interstitial fluid pressure (IFP) in solid tumours limits the targeted delivery of nanomedicines. We were previously able to relieve intra-tumoural IFP by low-frequency non-focused ultrasound (LFNFU) through ultrasonic targeted microbubble destruction (UTMD), improving the targeted delivery of FITC-dextran. However, the accumulation of nanoparticles of different sizes and the optimal acoustic pressure were not evaluated. In this study, we synthesised Cy5.5-conjugated mesoporous silica nanoparticles (Cy5.5-MSNs) of different sizes using a one-pot method. The Cy5.5-MSNs exhibited excellent stability and biosafety regardless of size. MCF7 tumour-bearing mice were subjected to UTMD over a range of acoustic pressures (0.5, 0.8, 1.5 and 2.0 MPa), and injected intravenously with Cy5.5-MSNs. Blood perfusion, tumour IFP and intra-tumoural accumulation of Cy5.5-MSNs were analysed. Blood perfusion and IFP initially rose, and then declined, as acoustic pressure intensified. Furthermore, UTMD significantly enhanced the accumulation of differentially sized Cy5.5-MSNs in tumour tissues compared to that of the control group, and the increase was sevenfold higher at an acoustic pressure of 1.5 MPa. Taken together, UTMD enhanced the infiltration and accumulation of Cy5.5-MSNs of different sizes in solid tumours by reducing intra-tumour IFP.
Graphical Abstract
The synthesis of Cy5.5-MSN and the effect of UTMD on its infiltration into tumours (produced using Figdraw, www.figdraw.com). (A) The synthesis route of Cy5.5-MSN. (B, C) The impact of UTMD on the infiltration of Cy5.5-MSN into tumours.
Author contributions
Conceptualisation: Yangcheng He, Yuyi Feng, Danxai Qiu and Jianhua Liu; methodology: Yangcheng He and Jianhua Liu; software: Yangcheng He, Yuyi Feng, Danxia Qiu, MinHua Lin, Zhiwen Hu, Xue Huang and Yan He; formal analysis: Yangcheng He, Hai Jin, MinHua Lin, Zhiwen Hu, Xue Huang and Meiqi Lai; investigation: Yangcheng He, Yuyi Feng, Danxia Qiu, Suihong Ma and Wenhui Jin; writing – original draft preparation: Yangcheng He, Yuyi Feng and Danxia Qiu; writing – review and editing: Yangcheng He, Hai Jin, Zhiwen Hu, Yan He and Jianhua Liu.
Ethical approval
These animal experiments adhered strictly to the guidelines provided by the National Institute of Health. The South China University of Technology’s Animal Ethics Committee granted approval for the care and utilisation of experimental animals (Approval No. AEC: 2021013). We maintained all animals in SPF-level environments, ensuring consistent temperature (25 ± 2 °C) and humidity (55 ± 5%), and provided sterilised commercial feed. To ensure the welfare of the animals, an optimal dose of pentobarbital was administered for anaesthesia. Diligent efforts were made to minimise animal distress and reduce the number of animals. For more detailed information, refer to the study protocol submitted to the Ethics Committee as part of the ethics approval application. Additionally, the conduct of this study was in strict alignment with the ARRIVE guidelines.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Data availability statement
Data available on request from the authors.