Prussian blue nanoparticle-based pH-responsive self-assembly for enhanced photothermal and chemotherapy of tumors.

In recent years, there has been growing interest in size-transformable nanoplatforms that exhibit active responses to acidic microenvironments, presenting promising prospects in the field of nanomedicine for tumor therapy. However, the design and fabrication of such size-adjustable nanotherapeutics pose significant challenges compared to size-fixed nanocomposites, primarily due to their distinct pH-responsive requirements. In this study, we developed pH-activated-aggregating nanosystems to integrate chemotherapy and photothermal therapy by creating size-transformable nanoparticles based on Prussian blue nanoparticles (PB NPs) anchored with acid-responsive polyoxometalates (POMs) quantum dots via electrostatic interactions (PPP NPs). Subsequently, we utilized doxorubicin (DOX) as a representative drug to formulate PPPD NPs. Notably, PPPD NPs exhibited a significant response to acidic conditions, resulting in changes in surface charge and rapid aggregation of PPP NPs. Furthermore, the aggregated PPP NPs demonstrated excellent photothermal properties under near-infrared laser irradiation. Importantly, PPPD NPs prolonged their retention time in tumor cells via a size-transformation approach. In vitro cellular assays revealed that the anticancer efficacy of PPPD NPs was significantly enhanced. The IC50 values for the PPPD NPs groupand the PPPD NPs + NIR group were 50.11 µg/mL and 30.9 µg/mL. Overall, this study introduces a novel strategy for cancer therapy by developing size-aggregating nano-drugs with stimuli-responsive properties, holding promise for improved therapeutic outcomes in future combination approaches involving photothermal therapy and chemotherapy.

Ratiometric Fluorescent Detection of Ultrasound-Regulated ATP Release: An Ultrasound-Resistant Cu,N-Doped Carbon Nanosphere.

Focused ultrasound, as a protocol of cancer therapy, might induce extracellular adenosine triphosphate (ATP) release, which could enhance cancer immunotherapy and be monitored as a therapeutic marker. To achieve an ATP-detecting probe resistant to ultrasound irradiation, we constructed a Cu/N-doped carbon nanosphere (CNS), which has two fluorescence (FL) emissions at 438 and 578 nm to detect ultrasound-regulated ATP release. The addition of ATP to Cu/N-doped CNS was conducted to recover the FL intensity at 438 nm, where ATP enhanced the FL intensity probably via intramolecular charge transfer (ICT) primarily and hydrogen-bond-induced emission (HBIE) secondarily. The ratiometric probe was sensitive to detect micro ATP (0.2-0.6 µM) with the limit of detection (LOD) of 0.068 µM. The detection of ultrasound-regulated ATP release by Cu,N-CNS/RhB showed that ATP release was enhanced by the long-pulsed ultrasound irradiation at 1.1 MHz (+37%, p < 0.01) and reduced by the short-pulsed ultrasound irradiation at 5 MHz (-78%, p < 0.001). Moreover, no significant difference in ATP release was detected between the control group and the dual-frequency ultrasound irradiation group (+4%). It is consistent with the results of ATP detection by the ATP-kit. Besides, all-ATP detection was developed to prove that the CNS had ultrasound-resistant properties, which means it could bear the irradiation of focused ultrasound in different patterns and detect all-ATP in real time. In the study, the ultrasound-resistant probe has the advantages of simple preparation, high specificity, low limit of detection, good biocompatibility, and cell imaging ability. It has great potential to act as a multifunctional ultrasound theranostic agent for simultaneous ultrasound therapy, ATP detection, and monitoring.

3D cell culture based on artificial cells and hydrogel under microgravity for bottom-up microtissue constructs.

The use of hydrogel as a filling medium to recombine dispersed microencapsulated cells to form an embedded gel-cell microcapsule complex is a new idea based on bottom-up tissue construction, which is benefit for cell distribution and of great significance for tissue construction research in vitro. In this experiment, sodium alginate and chitosan were used as the main materials, rat normal liver cell BRL-3A was used as the model cell to prepare "artificial cells". Silkworm pupa was used as raw material to extract silk fibroin solution, which was prepared by ultrasound to be the silk fibroin gel; silk fibroin hydrogel-microencapsulated hepatocyte embedded complex was then prepared by using silk fibroin gel as filling medium; the complex was cultured under three modes (static, shaking, and 3D microgravity), and the tissue forming ability of rat hepatocytes was investigated. The results showed that the microgravity culture condition can enhance the cell proliferation and promote the formation of cell colonies in the microcapsules; silk fibroin can form an embedded gel-cell microcapsule complex with microencapsulated cells, which provided mechanical support for the structure of the composite. We hope that this bottom-up construction system will have potential applications in the fields of cell culture and tissue construction.

A carboxymethyl lentinan layer by layer self-assembly system as a promising drug chemotherapeutic platform.

Surface functionalization of mesoporous silica nanoparticles (MSNs) has been proposed as an efficient strategy for enhancing the biocompatibility and efficiency of an MSN-based carrier platform. Herein, natural polyelectrolyte multilayers composed of poly-l-ornithine (PLO) and carboxymethyl lentinan (LC) were coated on the surface of MSNs through a layer-by-layer (LbL) self-assembly technique, and were characterized by ζ-potential, FTIR, 13C NMR, SEM, TEM, XRD, and TG. The prepared carrier presented alternating positive and negative potentials when coated with the polyelectrolytes, and the surface of MSN-PLO/LC was rougher compared to the naked MSNs. The biocompatibility tests, including cytocompatibility, hemocompatibility, and histocompatibility, showed that MSNs biocompatibility could be improved by modifying LC. A high loading and sustained release drug delivery system was constructed after loading doxorubicin (DOX) into the prepared MSN-PLO/LC, which exhibited significant anti-proliferative efficiency in human cervical cancer cell lines (Hela). Therefore, the PLO/LC LbL NPs (layer-by-layer self-assembled nanoparticles coated with PLO/LC layers) based on MSNs, which is easily prepared by electrostatic interactions, can be considered a promising drug chemotherapeutic platform and delivery technique for future human cervical cancer therapy.