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As a major component of tumor infiltration, tumor‐associated macrophages (TAMs) primarily promote the M2 phenotype of tumors in the tumor microenvironment. Additionally, the overexpression of anti‐phagocytic molecules in TAMs facilitates tumor cell evasion of TAMs’ phagocytic arrest. Therefore, there is an urgent need to develop a reliable strategy to reprogram TAMs for more effective anti‐tumor outcomes. In this study, innovative inhalable bioorthogonal gene‐editable microparticles (SPR) have been engineered that reprogram TAMs for lung cancer therapy based on spike‐covered sunflower sporopollenin exine capsules (SECs). These microparticles utilize SECs as delivery vehicles, with reduced palladium (Pd) nanoparticles on their surface carrying CRISPR/Cas9 lipid nanoparticles (LNP‐RNPs) that specifically knock down the anti‐phagocytic SIRPα gene on TAMs. The SPR microparticles employ a tripartite strategy to reprogram the TAMs: the physical stimulation through pollen spikes, the production of a Toll‐like receptor 7 agonist (imiquimod, IMD) via Pd‐mediated bioorthogonal catalysis, and the employment of CRISPR/Cas9 gene editing. In an orthotopic mouse model, the inhalation of SPR microparticles not only reprograms macrophages efficiently but also bolsters their tumor‐fighting abilities. Notably, the cured mice show no signs of recurrence even upon re‐exposure to the tumor, indicating a long‐lasting anti‐tumor effect. [ABSTRACT FROM AUTHOR]

Renal clearance is critical for nanodrug to avoid the long‐term body retention‐related side effects, while it is difficult to achieve efficient tumor accumulation and retention. The over‐developed lysosomes in cancer cells have become an emerging target for more precise and effective cancer therapy. Herein, a pH‐responsive reversible self‐assembled Cu2‐xSe‐BSA, which can be renal cleared under neutral or basic conditions, is developed for selectively targeted aggregation in cancer lysosomes with enhanced tumor accumulation and retention. Moreover, the aggregation of Cu2‐xSe‐BSA can enhance the photoacoustic imaging signal, photothermal therapy, and chemodynamic therapy capability. Cu2‐xSe‐BSA accumulated in lysosomes cannot only induce lysosomes swelling, but also generate reactive oxygen species in situ, causing lysosomal membrane permeabilization and finally lysosomal cell death. Notably, the assembled Cu2‐xSe‐BSA can dissociate to be renal clearable after the treatments are completed and left the acid tumor microenvironment, being of great significance both in scientific research and clinical trial. [ABSTRACT FROM AUTHOR]

Checkpoint blockade based immune therapy has shown to be effective but benefit only the minority of patients whose tumors have been pre-infiltrated by T cells. To overcome this obstacles, a PEG-modified Bi2Se3 nanocage (NC) loaded with imiquimod (R848), which could efficiently destroy the tumors thus producing enough tumor-associated antigens (TAA) and with the existence of R848, a toll-like-receptor-7 agonist, could generate strong anti-cancer immune responses is reported in this study. Moreover, immunogenic Bi2Se3 NC-PEG/R848 mediated photothermal therapy (PTT) sensitizes tumors to checkpoint inhibition mediated by a PD-L1 antibody, not only ablating cancer cells upon NIR laser but also causing strong anti-cancer immunity to suppress distant tumor growth post PTT. Both in vitro and in vivo experiments demonstrate that the Bi2Se3 NC-PEG/R848 could effectively activate a PTT-induced immune response as well as silence immune resistance based on PD-L1 checkpoint blockade to ablate the primary tumor and further inhibit the tumor metastasis. Bi2Se3 NC reported here exhibits high photothermal conversion efficiency and stability, as well as competent drug loading capacity with large hollow structures and high surface area. Our study not only provides a facial way to synthesize Bi2Se3 NC, but also offers an alternative strategy for tumor metastasis. [ABSTRACT FROM AUTHOR]

Improving the generation of reactive oxygen species (ROS) while consuming glutathione (GSH) is the main method for amplifying intracellular oxidative stress. However, in previous studies, it was normally necessary to combine two or more materials to achieve the effect of destroying the intracellular redox homeostasis. This made the preparation process relatively complicated. Herein, we designed ultra-small bismuth sulfide quantum dot (Bi2S3 QD)-doped hollow mesoporous Prussian blue (HMPB) (HMPB/Bi2S3) nanocubes for amplified tumor oxidative stress to augment photo-/radiotherapy. In addition to being photothermal materials, Prussian blue can be used as both a catalyst for the Fenton reaction and a consumer of GSH due to the multivalent state of iron. Ferrous ions (Fe(ii)) can produce toxic ROS-hydroxyl radicals (˙OH) with abundant hydrogen peroxide in the tumor cells by the Fenton reaction. Meanwhile, ferric ions (Fe(iii)) can oxidize the intracellular GSH to GSSG, thus depleting the concentration of GSH inside tumors. As a result, oxidative stress imbalance could be induced by the reversible redox property of Fe(ii/iii), thereby causing DNA damage and increasing the cell membrane permeability to realize enhanced photo-/radiotherapy. As a sensitizer for radiotherapy, ultra-small Bi2S3 QDs (3-5 nm) are doped in HMPB, thus improving the therapeutic effect by prolonging blood circulation and reducing systemic toxicity via kidney metabolism. Therefore, such a reversible HMPB/Bi2S3 nanocube is a promising therapeutic agent for amplified tumor oxidative stress to augment photo-/radiotherapy, which might show further applications in nanomedical science.

Recently, multifunctional clearable inorganic theranostic nanoparticles have been attracting more and more attention. Protein-based nanoparticles can be cleared by the hepatobiliary system efficiently. In this work, ultrasmall gadolinium oxide (Gd 2 O 3 ) nanoparticles, which possess the advantage of high longitudinal relaxation rate, were coated with bovine serum albumin (BSA). After the Gd 2 O 3 /BSA nanoparticles were linked with two-dimensional photothermal MoS 2 nanomaterials, the nanoparticles were also modified with hyaluronic acid (HA) through the disulfide bonds for tumor-targeting effect. As indicated by in vitro and in vivo studies, these Gd 2 O 3 /BSA@MoS 2 -HA nanoparticles could be rapidly degraded and excreted after reacting with glutathione (GSH) by the redox response, thus avoiding long-term toxicity. In addition, the cellular uptake study and in vivo multispectral optoacoustic tomography (MSOT), X-ray computed tomography (CT), and magnetic resonance (MR) triple-modal images demonstrated that Gd 2 O 3 /BSA@MoS 2 -HA nanoparticles exhibited a high tumor uptake effect after intravenous injection. Consequently, such clearable theranostic nanoparticles with multiple functions, which are applicable in multimodal imaging-guided cancer therapy, might show promise for applications in nanomedical science.

Rod-shape nanoplatform have received tremendous attention owing to their enhanced ability for cell internalization and high capacity for drug loading. MoS 2 , widely used in electronic devices, electrocatalysis, sensor and energy-storage, has been studied as photothermal agents over the years. However, the efficacy of rod-shape MoS 2 based photothermal agents for photothermal therapy has not been studied before. Here, a near-infrared (NIR) light-absorbing MoS 2 nanosheets coated mesoporous silica nanorods with human serum albumin (HSA) modifying and Ce6 loading (MSNR@MoS 2 -HSA/Ce6) were constructed for combined photothermal and photodynamic therapy. Methods : The near-infrared (NIR) light was used to trigger the synergistic anti-tumor therapy. In addition, breast cancer cell line was applied to evaluate the in vitro anti-tumor activity. The multi-modal imaging capacity and tumor-killing efficiency of the designed nanocomposites in vivo was also demonstrated with the 4T1 tumor-bearing mouse model. Results : These nanocomposites could not only perform NIR light triggered photodynamic therapy (PDT) and photothermal therapy (PTT), but also achieve in vivo fluorescence (FL) /multispectral optical tomography (MSOT)/X-ray computed tomography (CT) triple-model bioimaging. What's more, the rod-shape nanoplatform could be endowed with better anti-tumor ability based on the EPR effect and HSA-mediated active tumor targeting. At the same time, the hyperthermia generated by MoS 2 could synergistically improve the PDT effect with the acceleration of the blood flow, leading to the increase of the oxygen level in tumor tissue. Conclusion : MSNR@MoS 2 -HSA/Ce6 proves to be a promising multi-functional nanoplatform for effective treatment of tumor., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Radiotherapy (RT) is one of the most widely applied treatments for cancer therapy in clinics. Herein, we constructed innovative multifunctional nanotheranostic MnO2-mSiO2@Au-HA nanoparticles (MAHNPs) based on one-pot MnO2-mSiO2 nanohybrids (MNHs) and gold nanoparticles (AuNPs) for multispectral optoacoustic tomography (MSOT)/computed tomography (CT) and magnetic resonance (MR) imaging-guided hypoxia-maneuvered radiotherapy. The MNHs were prepared via a facile one-pot approach, which avoided the leakage of MnO2 nanoparticles and increased the synthetic efficiency. The Mn2+ ions triggered the breakdown of endogenous H2O2 to generate O2 to convert the hypoxic tumor micro-environment (TME), thus enhancing radiotherapy by self-supply oxygen. In addition, hyaluronic acid (HA) was employed to modify the surface of the MnO2-mSiO2@Au nanoparticles to improve their biocompatibility and cellular uptake. The well-designed nanoparticles could perform remarkable photothermal therapy (PTT) and hypoxia-maneuvered radiotherapy (RT) simultaneously and MSOT/CT/MR imaging. The in vivo studies showed that the MAHNPs achieved almost total suppression of tumor growth without observable recurrence, which raises new possibilities for clinical nanotheranostics with multimodal diagnostic and therapeutic coalescent design.

Recently, we developed ultrasmall molybdenum disulfide (MoS 2 ) quantum dots for computed tomography (CT) and multispectral optoacoustic tomography (MSOT) imaging-guided photothermal therapy (PTT). But, due to rapid body elimination and limited blood circulation time, the tumor uptake of the dots is low. In our study, this problem was solved via designing an amino-modified biodegradable nanomaterial based on MoS 2 quantum-dots-doped disulfide-based SiO 2 nanoparticles (denoted MoS 2 @ss-SiO 2 ) for multimodal application. By integrating the MoS 2 quantum dots into clearable SiO 2 nanoparticles, this nanoplatform with an appropriate particle size can not only degrade and excrete in a reasonable period induced by redox responsiveness of glutathione but also exhibit a high tumor uptake due to the longer blood circulation time. Moreover, hyaluronic acid and chlorin e6 (Ce6) were adsorbed on the outer shell for tumor-targeting effect and photodynamic therapy, respectively. So, this biodegradable and clearable theranostic nanocomposite, which is applicable in integrated fluorescence/CT/MSOT imaging-guided combined photothermal therapy (PTT) and photodynamic therapy, is very promising in biomedical applications in the future.