Surface-engineered nanobubbles with pH-/light-responsive drug release and charge-switchable behaviors for active NIR/MR/US imaging-guided tumor therapy

Xiao Zhi,Jia Zhou,Hualin Fu,Chunlei Zhang,Tianliang Li,Jie Song,Jiaqi Niu,Daxiang Cui

doi:10.1038/s41427-018-0094-6

Abstract

Active drug-loaded nanocarriers have been widely employed as efficient drug delivery systems for tumor theranostics. Herein, we report folate-mediated “all-in-one” nanobubbles for tumor-targeted NIR/MR/US imaging and combined chemo-photothermal therapy. The surface-engineered nanobubbles are constructed from oleylamine-/IR-780-loaded hollow structures, folate and the GdDTPA-BSA@5-FU complex via electrostatic adsorption and further filled with gas after freeze drying. DLS data show that the nanobubbles have a hydrodynamic diameter of 120.41 ± 18.30 nm. TEM observations show a hollow inner cavity and a shell thickness of approximately 10 nm. The relaxivity (r1) of the nanobubbles reaches 16.56 s−1/mM, indicating suitable features for use as a T1-weighted MR contrast agent. Moreover, due to the gas core inside, the nanobubbles are suitable for ultrasound contrast imaging. Interestingly, ξ-potential data and cumulative release measurements demonstrate that the nanobubbles undergo charge-switchable behaviors and pH-/light-sensitive drug-release behaviors after surface engineering, which could facilitate deep tumor penetration and accelerate drug release for efficient killing of cancer cells. In vivo trimodal imaging and chemo-photothermal therapy for MGC-803 tumor-bearing mice reveal selective tumor accumulation, long tumor retention, and enhanced antitumor behaviors. Therefore, the all-in-one nanobubbles could be applied for active tumor-targeting theranostics.

Highlights

To enhance anticancer efficacy and reduce the adverse side effects of anticancer drugs, drug-loaded nanocarriers have been employed as an efficient medium for cancer therapy[1,2]
We report folate (FA)-mediated, gadolinium (Gd3+)-labeled and IR-780/5-FU-loaded nanobubbles for tumor-targeted near infrared (NIR)/MR/Ultrasonic imaging (US) imaging and combined chemo-photothermal therapy
The prepared GdDTPA-Bovine serum albumin (BSA)@ 5-FU complex was surrounded on the surface to form a stable all-in-one nanoplatform

Summary

Introduction

To enhance anticancer efficacy and reduce the adverse side effects of anticancer drugs, drug-loaded nanocarriers have been employed as an efficient medium for cancer therapy[1,2]. Endowing controlled drug-release capacity in response to the tumor microenvironment or external stimulating signals[3,4,5,6,7]. Complete drug-loaded nanocarriers with enhanced tumor accumulation, integrated functions for diagnosis and therapy, efficient drug release and deep tumor penetration capacity are required. The surface modification progress leads to improved pharmacokinetics and pharmacodynamics profiles[8,9,10]. Based on this strategy, charge-switchable nanoparticles has been developed as a kind of efficient nanocarrier[11,12,13,14]. These nanoparticles can change surface charge from negative to positive in response to external

Methods

Results

Conclusion