Carrier-free multi-component self-assembled nano-systems have attracted widespread attention owing to their easy preparation, high drug-loading efficiency, and excellent therapeutic efficacy. Herein, MnAs-ICG nanospike was generated by self-assembly of indocyanine green (ICG), manganese ions (Mn²⁺), and arsenate (AsO₄³⁻) based on electrostatic and coordination interactions, effectively integrating the bimodal imaging ability of magnetic resonance imaging (MRI) and fluorescence (FL) imaging-guided synergistic therapy of photothermal/chemo/chemodynamic therapy within an “all-in-one” theranostic nano-platform. The as-prepared MnAs-ICG nanospike had a uniform size, well-defined nanospike morphology, and impressive loading capacities. The MnAs-ICG nanospike exhibited sensitive responsiveness to the acidic tumor microenvironment with morphological transformation and dimensional variability, enabling deep penetration into tumor tissue and on-demand release of functional therapeutic components. In vitro and in vivo results revealed that MnAs-ICG nanospike showed synergistic tumor-killing effect, prolonged blood circulation and increased tumor accumulation compared to their individual components, effectively resulting in synergistic therapy of photothermal/chemo/chemodynamic therapy with excellent anti-tumor effect. Taken together, this new strategy might hold great promise for rationally engineering multifunctional theranostic nano-platforms for breast cancer treatment.

A nanoparticle’s shape is a critical determinant of its biological interactions and therapeutic effectiveness. This study investigates the influence of shape on the performance of mesoporous silica nanoparticles (MSNs) in anticancer therapy. MSNs with spherical, rod-like, and hexagonal-plate-like shapes were synthesized, with particle sizes of around 240 nm, and their other surface properties were characterized. The drug loading capacities of the three shapes were controlled to be 47.46%, 49.41%, and 46.65%, respectively. The effects of shape on the release behaviors, cellular uptake mechanisms, and pharmacological behaviors of MSNs were systematically investigated. Through a series of in vitro studies using 4T1 cells and in vivo evaluations in 4T1 tumor-bearing mice, the release kinetics, cellular behaviors, pharmacological effects, circulation profiles, and therapeutic efficacy of MSNs were comprehensively assessed. Notably, hexagonal-plate-shaped MSNs loaded with PTX exhibited a prolonged circulation time (t_1/2 = 13.59 ± 0.96 h), which was approximately 1.3 times that of spherical MSNs (t_1/2 = 10.16 ± 0.38 h) and 1.5 times that of rod-shaped MSNs (t_1/2 = 8.76 ± 1.37 h). This research underscores the significance of nanoparticles’ shapes in dictating their biological interactions and therapeutic outcomes, providing valuable insights for the rational design of targeted drug delivery systems in cancer therapy.

Late-stage and advanced colorectal cancer (CRC) often prove to be resistant to current treatment regimens, due to the evolving tumor microenvironment. Chemotherapy-dominated multi-modal therapeutic strategies based on the specific CRC microenvironment open a new horizon for eradicating colorectal tumors. Here, in situ valence-transited arsenic nanosheets are developed as a multi-modal therapeutic platform by responding to the H₂S-enriched CRC microenvironment. Carrier-free pegylated nanosheets of pentavalent arsenic (As^V), aminooxyacetic acid (AOAA), and copper ion (Cu²⁺) are innovatively self-assembled via coordination with high loading content and good stability. As^V in pegylated arsenic nanosheets (CAA-PEG NSs) is rapidly released and reduced to trivalent arsenic (As^III) to exert its chemotherapy in the local tumor. Furthermore, the immunosuppressive microenvironment is thoroughly remodeled via H₂S depletion of As^V to As^III conversion and impairment of H₂S production by AOAA. Additionally, the in situ produced ultrasmall CuS nanoparticles exhibit photothermal activity against CRC under the guidance of photoacoustic imaging. This multi-modal therapeutic strategy, dominated by chemotherapy, completely inhibits CRC progression and prevents its relapse.

Background: Cardiovascular disease is one of the leading causes of death worldwide. The presence of atherosclerotic plaques in the arteries leads to continuous growth and obstruction of blood vessels, which ultimately leads to acute myocardial infarction and sudden cardiac death. Ultrasound-triggered GVs cavitation has great potential in plaque treatment due to its noninvasive nature and safety. Methods: In this work, we constructed a Hirudin–Gas Vesicle Recombinant Plasmid to achieve gene delivery using macrophage membrane/lipid membrane fusion bio-vesicles. Results: The bio-fusion vesicles retained the macrophage membrane protein integrin α4β1 to combine with vascular adhesion molecules highly expressed by inflammatory cells to achieve delivery; the Hirudin–Gas Vesicle Recombinant Plasmid could escape lysosomes and enter the nucleus to achieve highly efficient transfection; Hirudin and Gas Vesicles are exocytosed through cleavage peptide and exocytosis peptide, respectively; their pharmacological effects are linked and complementary. Gas vesicles can break up lesion plates with the assistance of in vitro ultrasound, and Hirudin achieves fragment ablation and anti-inflammatory and lipid regulation. Conclusions: GVs-HV@MM-Lipo exerts potent anti-atherosclerotic and anti-inflammatory effects with favorable safety. GVs-HV@Lipo reduces mice aortic arch plaque area by 17%, while GVs-HV@MM-Lipo+US achieves further plaque regression and improved hemodynamics. Our work opens up a new paradigm in the treatment of atherosclerosis with Chinese medicine.