Ball-in-ball ZrO₂nanostructure for simultaneous CT imaging and highly efficient synergic microwave ablation and tri-stimuli-responsive chemotherapy of tumors

Abstract

Combined thermo-chemotherapy displays outstanding synergically therapeutic efficiency when compared with standalone thermotherapy and chemotherapy. Herein, we developed a smart tri-stimuli-responsive drug delivery system involving X@BB-ZrO NPs (X represents loaded IL, DOX, keratin and tetradecanol) based on novel ball-in-ball-structured ZrO nanoparticles (BB-ZrO NPs). The microwave energy conversion efficiency of BB-ZrO NPs was 41.2% higher than that of traditional single-layer NPs due to the cooperative action of self-reflection and spatial confinement effect of the special two-layer hollow nanostructure. The tri-stimuli-responsive controlled release strategy indicate that integrated pH, redox and microwaves in single NPs based on keratin and tetradecanol could effectively enhance the specific controlled release of DOX. The release of DOX was only 8.1% in PBS with pH = 7.2 and GSH = 20 μM. However, the release could reach about 50% at the tumor site (pH = 5.5, GSH = 13 mM) under microwave ablation. The as-made X@BB-ZrO NPs exhibited perfect synergic therapy effect of chemotherapy and microwave ablation both in subcutaneous tumors (H22 tumor-bearing mice) and deep tumors (liver transplantation VX2 tumor-bearing rabbit model). There was no recurrence and death in the X@BB-ZrO + MW group during the therapy of subcutaneous tumors even on the 42 day. The growth rates in the deep tumor of the control, MW and X@BB-ZrO + MW groups were 290.1%, 14.1% and -42% 6 days after ablation, respectively. Dual-source CT was used to monitor the metabolism behavior of the as-made BB-ZrO NPs and traditional CT was utilized to monitor the tumor growth in rabbits. Frozen section examination and ICP results indicated the precise control of drug delivery and enhanced cytotoxicity by the tri-stimuli-responsive controlled release strategy. The ball-in-ball ZrO NPs with high microwave energy conversion efficiency were first developed for synergic microwave ablation and tri-stimuli-responsive chemotherapy, which may have potential applications in clinic.

Improved Surface-Enhanced Raman Scattering Properties of ZrO2 Nanoparticles by Zn Doping

“…On the other hand, it is helpful for understanding of the mechanism of the SERS phenomenon on the semiconductor substrate. As a nontoxic, and highly biocompatible SERS substrate, the applications of ZrO 2 nanophase materials have bright prospects in catalysis, biomedical, chemical analysis and other industries [27,28].…”

Nanobiotechnology‐enabled energy utilization elevation for augmenting minimally‐invasive and noninvasive oncology thermal ablation

“…It has been documented that tetradecanol as well as ionic liquid and anti‐drugs were co‐loaded in hollow or mesoporous ZrO 2 carriers that usually served as support for effectively delivering anti‐tumor drugs (Long et al, 2016; Mao et al, 2017; Y. Zhang, Xu, et al, 2020). The loaded tetradecanol with a low melting point (39°C–40°C) could confine ionic liquid and anti‐tumor drugs in porous or hollow carriers and prevent them leakage when circulating in blood, but only released at tumor that experienced MWA due to the solid–liquid phase change of tetradecanol (Long et al, 2016, 2017).…”

Nanoscale Metal‐Organic Frameworks: Synthesis, Biocompatibility, Imaging Applications, and Thermal and Dynamic Therapy of Tumors

“…Second, the heat diffusion range of existing microwave ablation technology is limited, and the heat is not easy to regulate, thus it is difficult to eliminate large tumors and eradicate sporadic lesions completely . With the development of nanomedicine, a series of nanosensitive materials have been used for MTT to improve the microwave heating efficiency, such as ball‐in‐ball ZrO 2 nanoparticles, layered MoS 2 nanoflowers, hollow polydopamine nanoparticles and ionic liquids in particular. Ionic liquid, as the most well‐known microwave heating material, has good microwave heating effect through the valid conversion from electromagnetic energy to thermal energy in limited space owing to its ionic properties and excellent polarizability .…”