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

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. A nanomaterial that can improve infrared, magnetic resonance and ultrasound imaging of tumors, while also delivering drugs for chemotherapy has been developed by researchers in China. Nanoparticles with an appropriate coating can attach exclusively to cancer cells. They can be imaged from outside the body, allowing doctors to identify the cancer’s location and track its spread, and can also carry drugs to be released when the particles reach their target. Combining diagnosis and therapy into a single step, known as theranostics, leads to better patient care. Daxiang Cui and co-workers from the Shanghai Jiao Tong University made nanoparticles that included gadolinium ions for magnetic resonance imaging, a fluorescent dye for imaging and the drug that is released when stimulated by laser light. These nanoparticles exhibited selective accumulation and long retention in tumors in mice. Gas filled nanobubbles are fabricated by surface-engineered progress with forming folate-mediated, gadolinium (Gd3+)-labelled and IR-780/5-FU loaded hollow structures. The nanobubbles progress capacity of NIR-/MR-/US-imaging in vitro. Importantly, the nanobubbles present charge-switchable behaviors when pH values changed from 7.4 to 5.0 and demonstrate pH-/light-sensitive drug release behaviors. Coupled with FA-targeting, the nanobubbles can be employed for efficient tri-modal imaging in vivo with selective tumor accumulation, long tumor retention time, and present enhanced anti-tumor activity with combined chemo-/photothermal therapy. Therefore, nanobubbles can act as excellent nanocarriers for active tumor targeting theranostics.