Self‐Propelled Enzymatic Nanomotors from Prodrug‐Skeletal Zeolitic Imidazolate Frameworks for Boosting Multimodel Cancer Therapy Efficiency

Abstract

Self-propelled nanomotors, which can autonomous propelled by harnessing others type of energy, have shown tremendous potential as drug delivery systems for cancer therapy. However, it remains challenging for nanomotors in tumor theranostics because of their structural complexity and deficient therapeutic model. Herein, glucose-fueled enzymatic nanomotors (GC6@cPt ZIFs) are developed through encapsulation of glucose oxidase (GOx), catalase (CAT), and chlorin e6 (Ce6) using cisplatin-skeletal zeolitic imidazolate frameworks (cPt ZIFs) for synergetic photochemotherapy. The GC6@cPt ZIFs nanomotors can produce O 2 through enzymatic cascade reactions for propelling the self-propulsion. Trans-well chamber and multicellular tumor spheroids experiments demonstrate the deep penetration and high accumulation of GC6@cPt nanomotors. Importantly, the glucose-fueled nanomotor can release the chemotherapeutic cPt and generate reactive oxygen species under laser irradiation, and simultaneously consume intratumoral over-expressed glutathione. Mechanistically, such processes can inhibit cancer cell energy and destroy intratumoral redox balance to synergistically damage DNA and induce tumor cell apoptosis. Collectively, this work demonstrates that the self-propelled prodrug-skeleton nanomotors with oxidative stress activation can highlight a robust therapeutic capability of oxidants amplification and glutathione depletion to boost the synergetic cancer therapy efficiency.

Application of Magnetic Micro/Nanomotors in Biomedicine

“…29 In some enzyme-driven MNMs, magnetic materials will also be added to control their movement direction to achieve targeted drug delivery as well as to enhance photodynamic therapy. 30,31 Enzyme-driven MNMs can also be used to detect DNA. 32 It is also feasible to apply the activity of double enzyme to MNMs.…”

“…Enzyme-driven MNMs have become promising devices in biomedicine due to their good biocompatibility and versatility as well as the high bioavailability of fuels . In some enzyme-driven MNMs, magnetic materials will also be added to control their movement direction to achieve targeted drug delivery as well as to enhance photodynamic therapy. , Enzyme-driven MNMs can also be used to detect DNA . It is also feasible to apply the activity of double enzyme to MNMs .…”

Black Titania Janus Mesoporous Nanomotor for Enhanced Tumor Penetration and Near-Infrared Light-Triggered Photodynamic Therapy

“…The Pearson's correlation coefficient for HTiPC nanomotor was ∼0.32, lower than that of HTiP (∼0. 46).…”

Multiporphyrinic architectures: Advances in structural design for photodynamic therapy

“…For example, incorporation of oxygen carrier for targeted delivery, in situ decomposition of H 2 O 2 using enzyme and catalyst, biomimetic photosynthesis of oxygen, inhibition of cell respiration, and surface modification with an active targeting ability. [55,128] The therapeutic efficiency of PDT is inhibited by the hypoxia microenvironment of tumor tissues. To reverse this issue, Xiao et al reported a novel oxygen evolving MOF complex through coating with a thin MnO 2 layer and cancer cell membrane for hypoxia reversion and active target (Figure 11A).…”