Tetramodal Imaging and Synergistic Cancer Radio-Chemotherapy Enabled by Multiple Component-Encapsulated Zeolitic Imidazolate Frameworks

Abstract

The abundant species of functional nanomaterials have attracted tremendous interests as components to construct multifunctional composites for cancer theranostics. However, their distinct chemical properties substantially require a specific strategy to integrate them in harmony. Here, we report the preparation of a distinctive multifunctional composite by encapsulating small-sized semiconducting copper bismuth sulfide (CBS) nanoparticles and rare-earth down-conversion (DC) nanoparticles in larger-sized zeolitic imidazolate framework-8 (ZIF8) nanoparticles, followed by loading an anticancer drug, doxorubicin (DOX). Such composites can be used for tetramodal imaging, including traditional computed tomography and magnetic resonance imaging and, recently, for photoacoustic imaging and fluorescence imaging. With a pH-responsive release of the encapsulated components, synergistic radio-chemotherapy with a high (87.6%) tumor inhibition efficiency is achieved at moderate doses of the CBS&DC-ZIF8@DOX composite with X-ray irradiation. This promising strategy highlights the extending capacity of zeolitic imidazolate frameworks to encapsulate multiple distinct components for enhanced cancer imaging and therapy.

Identifying Differing Intracellular Cargo Release Mechanisms by Monitoring In Vitro Drug Delivery from MOFs in Real Time

“…There are a significant number of studies describing the delivery of Dox by a diverse range of MOFs—it is likely the most commonly used drug molecule in this area—and it has allowed exemplification of strategies such as targeted tumor uptake, 34 , 35 stimuli-responsive release, 36 , 37 multimodal treatments, 38 , 39 and theranostics. 40 , 41 A large number of these reports focus on the delivery of Dox from nanoparticles and composites of ZIF-8, 34 , 38 , 39 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 in which tetrahedral Zn 2+ centers connect 2-methylimidazolate linkers into a sod net, 51 and UiO-66, 34 , 35 , 52 , 53 , 54 in which Zr 6 O 4 (OH) 4 (RCO 2 ) 12 secondary building units (SBUs) connect 1,4-benzenedicarboxylate (BDC) linkers into a fcu net. 55 In both cases, the small pore apertures—3.4 Å for ZIF-8 (up to 12.0 Å when flexibility 56 , 57 is taken into account) and 6.0 Å for UiO-66—seemingly preclude penetration of the Dox molecule, which has a maximum diameter of 15.4 Å, 58 into the porosity of the MOF.…”

Application of New Radiosensitizer Based on Nano-Biotechnology in the Treatment of Glioma

“…encapsulated small semiconductor copper bismuth sulfide (Cu 3 BiS 3 , CBS) nanoparticles and rare earth down-conversion (DC) nanoparticles in larger size zeolite imidazole skeleton-8 (ZIF8) nanoparticles and then loaded them with anticancer drugs Doxorubicin (DOX). Under X-ray irradiation, a moderate dose of CBS&DC-ZIF8@DOX composite material can achieve high (87.6%) tumor suppression efficiency and synergistic radiotherapy and chemotherapy ( 119 ).…”

GSH‐Responsive Radiosensitizers with Deep Penetration Ability for Multimodal Imaging‐Guided Synergistic Radio‐Chemodynamic Cancer Therapy

“…Owing to the lack of clear tumor boundaries, the adjacent normal tissues are inevitably damaged during X‐ray irradiation, which is a major limitation of RT. Multimodal imaging is increasingly gaining attention in cancer diagnostics, [ 21–23 ] and may overcome the above limitation. Fluorescence (FL) imaging in the near‐infrared FL (NIR)‐II (950–1700 nm) window has low photon absorption and scattering, negligible tissue autofluorescence, and high spatial resolution.…”