Real‐Time Imaging Tracking of Engineered Macrophages as Ultrasound‐Triggered Cell Bombs for Cancer Treatment

Abstract

Cell‐based drug delivery systems are a promising platform for tumor‐targeted therapy due to their high drug‐loading capacities and inherent tumor‐homing abilities. However, the real‐time tracking of these carrier cells and controlled release of the encapsulated drugs are still challenging. Here, ultrasound‐activatable cell bombs are developed by encapsulating doxorubicin (DOX) and phase transformable perfluoropentane (PFP) into hollow mesoporous organosilica nanoparticles (HMONs) to prepare DOX/PFP‐loaded HMONs (DPH), followed by internalization into macrophages (RAW 264.7 cells). The resulting cell bombs (DPH‐RAWs) can maintain viability and actively home to the tumor. Especially, their migration can be tracked in real time using ultrasound due to the vaporization of a small portion of PFP during cell incubation at 37 °C. After accumulation at the tumor site, the further vaporization of remaining PFP can be triggered by a short‐pulsed high intensity focused ultrasound (HIFU) sonication, resulting in the generation of several large microbubbles, which destroys DPH‐RAWs and allows drug release out of these cells. The DPH‐RAWs combined with short‐pulsed HIFU sonication significantly inhibit tumor growth and prolong survival of tumor‐bearing mice. In conclusion, this study provides a new approach to cell‐based drug delivery systems for real‐time tracking of their migration and targeted cancer treatment.

Comprehensive review on ultrasound-responsive theranostic nanomaterials: mechanisms, structures and medical applications

“…In this case, it was possible to use macrophages that migrated to the tumor location as targeted cargo delivery systems. Under short-pulsed HIFU sonication, MBs were formed which destroyed the nanostructures and the cells at the same time leading to drug release [ 594 ].…”

Cell‐Based Bio‐Hybrid Delivery System for Disease Treatments

“…Xu et al have utilized ultrasound‐mediated rupture to realize drug release from macrophage carrier (Figure 3G). [ 55 ] Chemotherapy DOX and perfluoropentane (PFP) were loaded into hollow mesoporous organosilica nanoparticles (HMONs), which were further internalized into macrophages for active homing to tumor tissues. PFP functioned as an ultrasonography imaging‐agent for tracking macrophage migration, and evaporated to disrupt macrophage vehicle upon ultrasound sonication for releasing chemotherapy drugs.…”

Intelligent Pore Switch of Hollow Mesoporous Organosilica Nanoparticles for High Contrast Magnetic Resonance Imaging and Tumor-Specific Chemotherapy

“…It is well-known that large-sized DDSs are confronted with short blood circulation and fast RES uptake, resulting in poor tumor accumulation, so small-sized (especially sub-50 nm) MONs are highly desirable for effective tumor-targeted drug delivery on account of their increased enhanced permeability and retention (EPR) effect. ,, A common concern about sub-50 nm MONs is their relatively low drug loading content. Although the emerging hollow-structured MONs (HMONs) with an internal cavity provide an enlarged room for drug encapsulation, the entrapped drug molecules easily leak away through the interpenetrated pore channels of HMONs, thus conversely lowering down the net drug loading efficiency. − Worse, the premature drug leakage during blood circulation may cause unwanted toxicity to normal tissues and cells, which aggravates the side effects. , In this regard, a convenient pore blocking strategy involving the use of a powerful gatekeeper is urgently needed to be determined to prevent potential drug leakage from sub-50 nm HMONs for maximizing their drug loading content. The gatekeeper must possess an imaging functionality, benefiting the positioning of tumor location and monitoring of drug release.…”

“…23−25 Worse, the premature drug leakage during blood circulation may cause unwanted toxicity to normal tissues and cells, which aggravates the side effects. 26,27 In this regard, a convenient pore blocking strategy involving the use of a powerful gatekeeper is urgently needed to be determined to prevent potential drug leakage from sub-50 nm HMONs for maximizing their drug loading content. The gatekeeper must possess an imaging functionality, benefiting the positioning of tumor location and monitoring of drug release.…”