Search for: All records

Proteins can template the heterogeneous nucleation and growth of size-confined nanocrystals. However, protein-templated mineralization often leads to particles that exhibit low colloidal stability, poor crystal quality, and/or diminished photoluminescence. Here, we report protein cage–spherical nucleic acids (SNAs) that can be used as nanoreactors for quantum dot (QD) synthesis and subsequent intracellular delivery. The resulting QD-SNA structures are monodisperse, colloidally stable, and photoluminescent in aqueous solution. The nanoreactors were prepared using two different proteins (~10 and 12 nanometers in diameter), and CdS, CdSe, and PbSe nanocrystals were synthesized. Moreover, the extent of surface defects and crystallinity depends on the relative concentrations of ionic precursors, which control the growth rate and the number of ionic vacancies. By optimizing conditions, CdS-SNAs that exhibit near-zero reabsorption loss were synthesized. Last, QD-SNAs exhibit enhanced cellular uptake and minimal cytotoxicity when compared to commercial QD-protein conjugates, making them potentially useful in bioimaging and diagnostic applications. 

Abstract Abnormal cancer metabolism causes hypoxic and immunosuppressive tumor microenvironment (TME), which limits the antitumor efficacy of photodynamic therapy (PDT). Herein, we report a photosensitizing nanoscale metal–organic layer (MOL) with anchored 3‐bromopyruvate (BrP), BrP@MOL, as a metabolic reprogramming agent to enhance PDT and antitumor immunity. BrP@MOL inhibited mitochondrial respiration and glycolysis to oxygenate tumors and reduce lactate production. This metabolic reprogramming enhanced reactive oxygen species generation during PDT and reshaped the immunosuppressive TME to enhance antitumor immunity. BrP@MOL‐mediated PDT inhibited tumor growth by >90 % with 40 % of mice being tumor‐free, rejected tumor re‐challenge, and prevented lung metastasis. Further combination with immune checkpoint blockade potently regressed the tumors with >98 % tumor inhibition and 80 % of mice being tumor‐free. 

Abstract Although sonodynamic therapy (SDT) has shown promise for cancer treatment, the lack of efficient sonosensitizers (SSs) has limited the clinical application of SDT. Here, a new strategy is reported for designing efficient nano‐sonosensitizers based on 2D nanoscale metal–organic layers (MOLs). Composed of Hf‐oxo secondary building units (SBUs) and iridium‐based linkers, the MOL is anchored with 5,10,15,20‐tetra(p‐benzoato)porphyrin (TBP) sensitizers on the SBUs to afford TBP@MOL. TBP@MOL shows 14.1‐ and 7.4‐fold higher singlet oxygen (¹O₂) generation than free TBP ligands and Hf‐TBP, a 3D nanoscale metal–organic framework, respectively. The¹O₂generation of TBP@MOL is enhanced by isolating TBP SSs on the SBUs of the MOL, which prevents aggregation‐induced quenching of the excited sensitizers, and by triplet–triplet Dexter energy transfer between excited iridium‐based linkers and TBP SSs, which more efficiently harnesses broad‐spectrum sonoluminescence. Anchoring TBP on the MOL surface also enhances the energy transfer between the excited sensitizer and ground‐state triplet oxygen to increase¹O₂generation efficacy. In mouse models of colorectal and breast cancer, TBP@MOL demonstrates significantly higher SDT efficacy than Hf‐TBP and TBP. This work uncovers a new strategy to design effective nano‐sonosensitizers by facilitating energy transfer to efficiently capture broad‐spectrum sonoluminescence and enhance¹O₂generation.