Evading Doxorubicin-Induced Systemic Immunosuppression Using Ultrasound-Responsive Liposomes Combined with Focused Ultrasound.

Doxorubicin (DOX) is a representative anticancer drug with a unique ability to induce immunogenic cell death of cancer cells. However, undesired toxicity on immune cells has remained a significant challenge, hindering the usage of DOX in cancer immunotherapy. Here, we report a combined therapy to avoid the off-target toxicity of DOX by adapting ultrasound-responsive liposomal doxorubicin and focused ultrasound exposure.

Dissolving microneedles for long-term storage and transdermal delivery of extracellular vesicles.

Extracellular vesicles (EVs) have shown great potential in disease diagnosis and treatment; however, their clinical applications remain challenging due to their unsatisfactory long-term stability and the lack of effective delivery strategies. In this study, we prepared human adipose stem cell-derived EV (hASC-EV)-loaded hyaluronic acid dissolving microneedles (EV@MN) to investigate the feasibility of EVs for their clinical applications. The biological activities of the EVs in this formulation were maintained for more than six months under mild storage conditions, especially at temperatures lower than 4 °C.

Chemiluminescence resonance energy transfer-based immunostimulatory nanoparticles for sonoimmunotherapy.

Sonodynamic therapy (SDT) has recently emerged as a promising alternative to photodynamic therapy because of its applicability in treating deeply located tumors accessible by ultrasound (US). However, the therapeutic potential of conventional sonosensitizers is limited by the low quantum yield of reactive oxygen species (ROS) and poor immune responses eliciting canonical apoptosis of cancer cells. Herein, we report chemiluminescence resonance energy transfer (CRET)-based immunostimulatory nanoparticles (iCRET NPs) for sonoimmunotherapy, which not only amplify the ROS quantum yield of sonosensitizers but also generate carbon dioxide (CO) bubbles to induce immunogenic cell death in the tumor microenvironment (TME).

Gold-installed hyaluronic acid hydrogel for ultrasound-triggered thermal elevation and on-demand cargo release.

The temporal and quantitative control of the cargo release is a challenging issue in the application of hydrogels for cancer therapy. Here, we report hyaluronic acid hydrogel-based depot that provides ultrasound-triggered thermal elevation and on-demand cargo release. The hyaluronic acid hydrogel was developed by employing the gold cluster as a sonothermal crosslinker which was grown on the cargo to prevent its undesired leakage until ultrasound-induced dissociation.

Carboxymethyl dextran-based nanocomposites for enhanced chemo-sonodynamic therapy of cancer.

Glutathione (GSH), a tripeptide abundant in the cancer cells, inhibits the cytotoxic effect of reactive oxygen species (ROS) and is associated with anti-apoptosis, thus facilitating tumor growth. Here, we report GSH-depleting carboxymethyl dextran nanocomposites for chemo-sonodynamic therapy for cancer. The nanocomposite is composed of the TiO-based core as the sonosensitizer, MnO coat as the GSH-consuming chemosensitizer, and carboxymethyl dextran as the hydrophilic shell.

Engineering approaches for effective therapeutic applications based on extracellular vesicles.

The biological significance of extracellular vesicles (EVs) as intercellular communication mediators has been increasingly revealed in a wide range of normal physiological processes and disease pathogenesis. In particular, regenerative and immunomodulatory EVs hold potential as innate biotherapeutics, whereas pathological EVs are considered therapeutic targets for inhibiting their bioactivity. Given their ability to transport functional cargos originating from the source cells to target cells, EVs can also be used as a therapeutic means to deliver drug molecules.

Necroptosis-Inducible Polymeric Nanobubbles for Enhanced Cancer Sonoimmunotherapy.

Necroptosis, caspase-independent programmed necrosis, has emerged as a therapeutic target to make dying cancer cells stimulants for antitumor immune responses. The clinical translations exploiting necroptosis, however, have been limited since most cancer cells downregulate receptor-interacting protein kinase 3 (RIPK3) as a key enzyme for necroptosis. Herein, nanobubbles (NBs) that can trigger RIPK3-independent necroptosis, facilitating cell-membrane rupture via the acoustic cavitation effect are reported.

Preparation of gradient polyacrylate brushes in microchannels.

Gradient poly(2-hydroxyethyl methacrylate) brushes were synthesized by surface-initiated atom transfer radical polymerization (ATRP) confined within a microfluidic system on a silicon wafer. For ATRP, surface initiator, 11-((2-bromo, 2-methyl) propionyloxy) undecyltrichlorosilane (BUC), was synthesized, and allowed to self-assemble in a monolayer on the Si wafer, as analyzed by XPS to confirm the presence of an ester group of BUC. A solution containing 2-hydroxyethylmethacrylate, Cu catalyst, and bipyridin was allowed to flow in a microchannel and polymerize, resulting in the brushes with a gradient of thickness on the Si wafer.