CuPc-Fe@BSA nanocomposite: Intracellular acid-sensitive aggregation for enhanced sonodynamic and chemo-therapy.

Due to their rigid π-conjugated macrocyclic structure, organic sonosensitizers face significant aggregation in physiological conditions, hindering the production of reactive oxygen species (ROS). An acid-sensitive nanoassembly was developed to address this issue and enhance sonodynamic therapy (SDT) and emission. Initially, copper phthalocyanine (CuPc) was activated using a H2SO4-assisted hydrothermal method to introduce multiple functional groups (-COOH, -OH, and -SO3H), disrupting strong π-π stacking and promoting ROS generation and emission. Subsequently, negatively charged CuPc-SO4 was incorporated into bovine serum albumin (BSA) to form CuPc-Fe@BSA nanoparticles (10 nm) with Fe3+ ions serving as linkers. In acidic conditions, protonation of CuPc-SO4 and BSA weakened the interactions, leading to Fe3+ release and nanostructure dissociation. Protonated CuPc-SO4 tended to self-aggregate into nanorods. This acidity-sensitive aggregation is vital for achieving specific accumulation within the tumor microenvironment (TME), thereby enhancing retention and SDT efficacy. Prior to this, the nanocomposites demonstrated cycling stability under neutral conditions. Additionally, the released Fe ions exhibited mimicry of glutathione peroxidase and peroxidase activity for chemotherapy (CDT). The synergistic effect of SDT and CDT increased intracellular oxidative stress, causing mitochondrial injury and ferroptosis. Furthermore, the combined therapy induced immunogenic cell death (ICD), effectively activating anticancer immune responses and suppressing metastasis and recurrence.

Porous Molybdenum Nitride Nanosphere as Carrier-Free and Efficient Nitric Oxide Donor for Synergistic Nitric Oxide and Chemo/Sonodynamic Therapy.

Given its abundant physiological functions, nitric oxide (NO) has attracted much attention as a cancer therapy. The sensitive release and great supply capacity are significant indicators of NO donors and their performance. Here, a transition metal nitride (TMN) MoN@PEG is adopted as an efficient NO donor. The release process starts with H+-triggered denitrogen owing to the high electronegativity of the N atom and weak Mo-N bond. Then, these active NHx are oxidized by O2 and other reactive oxygen species (ROS) to form NO, endowing specific release to the tumor microenvironment (TME). With a porous nanosphere structure (80 nm), MoN@PEG does not require an extra carrier for NO delivery, contributing to ultrahigh atomic utilization for outstanding release ability (94.1 ± 5.6 µM). In addition, it can also serve as a peroxidase and sonosensitizer for anticancer treatment. To further improve the charge separation, MoN-Pt@PEG was prepared to enhance the sonodynamic therapy (SDT) effect. Accordingly, ultrasound (US) further promotes NO generation due to more ROS generation, facilitating in situ peroxynitrite (·ONOO-) generation with great cytotoxicity. At the same time, the nanostructure also degrades gradually, leading to high elimination (94.6%) via feces and urine within 14-day. The synergistic NO and chemo-/sono-dynamic therapy brings prominent antitumor efficiency and further activates the immune response to inhibit metastasis and recurrence. This work develops a family of NO donors that would further widen the application of NO therapy in other fields.

Plasmonic Bi nanoparticles encapsulated by N-Carbon for dual-imaging and photothermal/photodynamic/chemo-therapy.

In this work, the plasmonic Bi@N-Carbon@PEG-DOX nanocomposites were constructed to integrate the imaging and synergistic therapy in one nanoplatform. Here, Bi nanoparticles were encapsulated into the N-doped carbon nanomaterials via a simple solvothermal method. The accumulated adjacent semimetal Bi nanoparticles in Bi@N­carbon enhanced the local surface plasmon resonance (LSPR) to make the great NIR harvest and high photothermal converting efficiency (52.3%, Bi@C-2). And that also was confirmed by the Finite Difference Time Domain (FDTD) calculation. Moreover, the LSPR would induce the hot charges (polarization charges), which were captured by O2 and H2O molecules to form ROS for photodynamic therapy (PDT). And the heterostructure of Bi and N­carbon further improved the effective segregation of the hot charges, making the 6.9 times ROS production (Bi@C-2) in comparing with pure Bi sample. In view of the ultrahigh X-ray attenuation coefficient of Bi and great photothermal effect, Bi@N-Carbon@PEG possessed the outstanding computerized tomography (CT) and photothermal imaging capacity. Meanwhile, they also exhibited the favourable biodegradation ability, inducing the elimination via urine and feces within 14 day. The integration of the multi-model (CT and Thermal) imaging and the PTT/PDT/chemotherapy makes Bi@N­carbon@PEG-DOX to be a potential candidate for cancer treatment.