Extracellular nanovesicles (ENV) released by many cells contain lipids, proteins, and nucleic acids that contribute to intercellular communication. ENVs have emerged as biomarkers and therapeutic targets but they have also been explored as drug delivery vehicles. However, for the latter application, clinical translation has been limited by low yield and inadequate targeting effects. ENV vectors with desired targeting properties can be produced from parental cells engineered to express membrane-bound targeting ligands, or they can be generated by fusion with targeting liposomes; however, neither approach has met clinical requirements. In this study, we demonstrate that mechanical extrusion of approximately 10 cells grafted with lipidated ligands can generate cancer cell-targeting ENV and can be prepared in approximately 1 hour. This rapid and economic approach could pave the way for clinical implementation in the future. A new and rapid method for production of drug-targeting nanovesicles has implications for cancer treatment by chimeric antigen receptor T cells and other therapies. .
Nanosized drug delivery systems have offered promising approaches for cancer theranostics. However, few are effective to simultaneously maximize tumor-specific uptake, imaging, and therapy in a single nanoplatform. Here, we report a simple yet stimuli-responsive anethole dithiolethione (ADT)-loaded magnetic nanoliposome (AML) delivery system, which consists of ADT, hydrogen sulfide (HS) pro-drug, doped in the lipid bilayer, and superparamagnetic nanoparticles encapsulated inside. HepG2 cells could be effectively bombed after 6 h co-incubation with AMLs. For in vivo applications, after preferentially targeting the tumor tissue when spatiotemporally navigated by an external magnetic field, the nanoscaled AMLs can intratumorally convert to microsized HS bubbles. This dynamic process can be monitored by magnetic resonance and ultrasound dual modal imaging. Importantly, the intratumoral generated HS bubbles imaged by real-time ultrasound imaging first can bomb to ablate the tumor tissue when exposed to higher acoustic intensity; then as gasotransmitters, intratumoral generated high-concentration HS molecules can diffuse into the inner tumor regions to further have a synergetic antitumor effect. After 7-day follow-up observation, AMLs with magnetic field treatments have indicated extremely significantly higher inhibitions of tumor growth. Therefore, such elaborately designed intratumoral conversion of nanostructures to microstructures has exhibited an improved anticancer efficacy, which may be promising for multimodal image-guided accurate cancer therapy.
Microcontainers with embedded superparamagnetic nanoparticles can be changed into bubble microreactors upon treatment with an alternating magnetic field, which acts as a remote trigger for the release of encapsulated material. Exchange of an arginine solution inside and H2O2 solution outside the microcontainers generates NO gas. The microstructure combines ultrasound diagnostic and NO therapeutic functionalities.
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