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Organic nanocrystals, particularly those composed of conjugated molecules, hold immense potential for various applications. However, their practical utility is often hindered by the challenge of achieving stable aqueous dispersions, which are essential for biological compatibility and effective delivery. This study introduces a novel and versatile strategy for preparing stable aqueous organic nanocrystals using a modified reprecipitation method. We demonstrate the broad applicability of this approach by successfully preparing a diverse library of nanocrystals from 27 conjugated molecules. Our findings reveal a charge-balanced aggregation mechanism for nanocrystal formation, highlighting the crucial role of surface charge in controlling particle size and stability. Based on this mechanism, we establish a comprehensive molecular combination strategy that directly links molecular properties to colloidal behaviour, enabling the straightforward prediction and preparation of stable aqueous dispersions without the need for excipients. This strategy provides a practical workflow for tailoring the functionality of these nanocrystals for a wide range of applications. To illustrate their therapeutic potential, we demonstrate the enhanced efficacy of these nanocrystals in treating acute ulcerative colitis, myocardial ischemia/reperfusion injury, and cancer in mouse models. This work paves the way for developing next-generation nanomaterials with tailored functionalities for diverse biomedical applications. [Display omitted] • Bridging Disciplines: This research bridges crystal engineering and colloid science by achieving aqueous stability of organic nanocrystals. • New Design Rules: Charge-balanced aggregation links molecular properties to colloidal behaviour for stable nanocrystals. • Predictive Strategy: A strategy for identifying suitable molecular combinations for aqueous organic nanocrystals. • Practical Workflow: A practical workflow for preparing diverse aqueous organic nanocrystals. • Functional Control & Applications: Diverse molecular combinations enable control over nanocrystal functionality for bioapplications. [ABSTRACT FROM AUTHOR]

• Develop a carrier-free ternary immunostimulant to enhance the STING activation. • Induction of photodynamic DNA damage by producing reactive oxygen species. • Amplify the STING signal by the release of cytosolic DNA and STING agonist. • Inhibition of PI3K pathway to downregulate T regulatory cells (Tregs) • Eradicate colorectal cancer by cascade activating T cells and decreasing Tregs. Stimulator of interferon genes (STING) plays an essential role in initiating the innate anti-tumor immunity, which could be activated by the cytosolic DNA but suppressed by the immunosuppressive cells. In this work, a self-delivery ternary immunostimulant (designated as ImmSt) is fabricated for colorectal cancer therapy with the immunological cascades of photodynamic DNA damage and T regulatory cell inhibition. Among which, the photosensitizer of Chlorin e6 (Ce6), the STING agonist of 5,6-dimethylxanthine-4-acetic acid (DMXAA) and the phosphatidylinositol 3-kinases (PI3Ks) inhibitor of ZSTK474 could self-assemble into uniform nanomedicine without drug excipient, which enhances the drug stability, bioavailability and pharmacological activities. Importantly, the photodynamic therapy (PDT) effect of ImmSt produces enormous reactive oxygen species to ablate tumor cells, and also triggers the release of cytosolic DNA to amplify the STING signal in combination with the STING agonist. Moreover, ImmSt is able to induce a systemic anti-tumor immunity by the cascade activation of T cells and the decrease of T regulatory cells. In vitro and in vivo results confirm that ImmSt can efficiently eradicate colorectal cancer without severe side effects, which may provide a sophisticated mechanism for immunotherapy in consideration of the immune activation and immunosuppressive factors. [ABSTRACT FROM AUTHOR]

The 32P radioisotope, with a half-life of 14.3 days and an energy level of 1.71 MeV, has diverse applications in medicine and research. Consequently, producing a carrier-free 32P radioisotope characterized by high radiochemical and radionuclide purity is imperative. Two primary methods for generating 32P radioisotopes exist: irradiating phosphorus through the nuclear reaction (n,γ) or irradiating sulfur through the nuclear reaction (n,p). Using sulfur as a target material provides several advantages. Besides the fact that the chemical element produced after irradiation (32P) differs from the irradiated element (32S), it also produces a32P radioisotope with a higher specific activity than using 31P as the target. The production of the radioisotope 32P from sulfur employs the dry distillation method, capitalizing on sulfur's easily sublimated nature. The volatility of sulfur when heated makes it easy to separate the resulting sulfur and radioisotope 32P without the need for additional reagents. This research aims to establish a practical method for producing the 32P radioisotope using the dry distillation technique. The dry distillation method utilizes a quartz ampoule containing a mixture of 32P and 35S radionuclides, a distillation tube wrapped with heating tape, and a condenser to collect the distilled sulfur. Sulfur, serving as the target material, undergoes irradiation in the reactor at the Central Irradiation Position (CIP) through the 32S(n,p)32P nuclear reaction with a fast neutron flux of 5.380 × 1013 n/cm2.sec. Separation is achieved through distillation at a temperature of 440 °C. The residual separation products are then dissolved in a 0.1 N HCl solution. The purification process involves using an AG50 WX8 cation exchange resin column, which is pre-conditioned with 0.1 N HCl. The resulting eluate contains the 32P radioisotope. The radiochemical purity of the 32P radioisotope is analyzed using thin-layer chromatography (TLC). In this analysis, a PEI Cellulose plate serves as the stationary phase, and a KH 2 PO 4 solution acts as the mobile phase. This vacuum-free distillation method successfully separates the 32P radioisotope from sulfur, achieving a separation efficiency of 55.1 ± 9.9% (n = 7). The average activity produced after the purification process is 5.690E+10 Bq. Purifying the 32P radioisotope results in a radiochemical purity of 99.97% at Rf 0.7110, as orthophosphate, the radionuclide purity exceeds 99%. • Sulfur Distillation is a process used to isolate Sulfur from the 32P radioisotope produced after irradiation in a reactor. • Production of 32P radioisotopes conducted by the Indonesian Research Center for Radioisotope Technology. [ABSTRACT FROM AUTHOR]

The combination of immunotherapy and chemotherapy to ablate tumors has attracted substantial attention due to the ability to simultaneously elicit antitumor immune responses and trigger direct tumor cell death. However, conventional combinational strategies mainly focus on the employment of drug carriers to deliver immunomodulators, chemotherapeutics, or their combinations, always suffering from complicated preparation and carrier-relevant side effects. Here, the fabrication of bacterial flagellum-drug nanoconjugates (FDNCs) for carrier-free immunochemotherapy is described. FDNCs are simply prepared by attaching chemotherapeutics to amine residues of flagellin through an acid-sensitive and traceless cis-aconityl linker. By virtue of native nanofibrous structure and immunogenicity, bacterial flagella not only show long-term tumor retention and highly efficient cell internalization, but also provoke robust systemic antitumor immune responses. Meanwhile, conjugated chemotherapeutics exhibit an acid-mediated release profile and durable intratumoral exposure, which can induce potent tumor cell inhibition via direct killing. More importantly, this combination is able to augment immunoactivation effects associated with chemotherapy-enabled immunogenic tumor cell death to further enhance antitumor efficacy. By leveraging the innate response of the immune system to pathogens, the conjugation of therapeutic agents with self-adjuvant bacterial flagella provides an alternative approach to develop carrier-free nanotherapeutics for tumor immunochemotherapy., (© 2023 Wiley-VCH GmbH.)