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Ultrasonics. 2018 Jul;87:82-90. doi: 10.1016/j.ultras.2018.02.003. Epub 2018 Feb 5.

Dual-functionalized nanoparticles loaded microbubbles for enhancement of drug uptake.

Author information

1
Department of Medicine Ultrasonics, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: lyjia@smu.edu.cn.
2
Department of Medicine Ultrasonics, Nanfang Hospital, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research, Cancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou, China.
3
Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, China.
4
Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research, Cancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou, China.
5
Department of Medicine Ultrasonics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
6
Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research, Cancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou, China. Electronic address: ningmengquan@gmail.com.

Abstract

The application of microbubble (MB)-assisted ultrasound (US) can combine the advantages of real-time imaging and targeted drug delivery. However, the drug loading capacity of MB is limited restricting its application in antitumor procedure. In contrast, nanoparticles (NPs) can carry drugs more efficiently, but adverse side effect induced by unspecific accumulation can not be ignored. Herein, we developed a dual-functionalized NP loaded MB to investigate its potential feasibility for tumor-targeted drug delivery. Firstly, we prepared NPs using heparin as backbone. Targeting ligand folate and cell-penetrating ligand Tat peptide were conjugated to the backbone to deliver paclitaxel (H-F-Tat-P NPs). Subsequently, the dual-functionalized NPs were incorporated with MBs via avidin-biotin linkage to fabricate H-F-Tat-P NPs loaded MBs (NPs-loaded MBs). The combined strategy can take profit of dual functionalities from NPs and sonoporation effect from MBs triggered by US. The prepared NPs have been characterized. The excellent cellular uptake of NPs were qualitative and quantitative analysis by flow cytometry and confocal microscope, the results indicated that it was attributed to not only dual functionalities but also US effect. Foremost, the NPs-loaded MBs combined with US exhibited significant cytotoxicity on both folate receptor (FR) overexpressing and deficiency cells. The combination of dual-functionalized NPs and MBs with US is expected to be a promising strategy for targeted anticancer drug delivery and ultrasound imaging simultaneously.

KEYWORDS:

Drug uptake enhancement; Dual-functionalized nanoparticles; Microbubbles; Ultrasound

PMID:
29475016
DOI:
10.1016/j.ultras.2018.02.003
[Indexed for MEDLINE]

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