Inhalable GSH-Triggered Nanoparticles to Treat Commensal Bacterial Infection in In Situ Lung Tumors

Abstract

Bacterial infection has been considered one of the primary reasons for low survival rate of lung cancer patients. Herein, we demonstrated that a kind of mesoporous silica nanoparticles loaded with anticancer drug doxorubicin (DOX) and antimicrobial peptide HHC36 (AMP) (MSN@DOX-AMP) can kill both commensal bacteria and tumor cells under GSH-triggering, modulating the immunosuppressive tumor microenvironment, significantly treating commensal bacterial infection, and eliminating in situ lung tumors in a commensal model. Meanwhile, MSN@DOX-AMP encapsulated DOX and AMP highly efficiently via a combined strategy of physical adsorption and click chemistry and exhibited excellent hemocompatibility and biocompatibility. Importantly, MSN@DOX-AMP could be inhaled and accumulate in lung by a needle-free nebulization, achieving a better therapeutic effect. This system is expected to serve as a straightforward platform to treat commensal bacterial infections in tumors and promote the translation of such inhaled GSH-triggered MSN@DOX-AMP to clinical treatments of lung cancer.

Diagnosing Orthotopic Lung Tumor Using a NTR-Activatable Near-Infrared Fluorescent Probe by Tracheal Inhalation

“…All animal experiments were conducted in accordance with the Code of Practice for Animal Management already published by the Ministry of Health of the People's Republic of China (document no. 55,2001) and performed in accordance with the "Guide for the Care and Use of Laboratory Animals" of China Pharmaceutical University. IR-NO 2 , a product we synthesized containing only the NTR response fragment and fluorophore, was used to image subcutaneous tumors by tail vein administration, and it was found that IR-ABS not only binds more rapidly to subcutaneous tumors than products without the CAIXi fragment but also avoids imaging interference from liver metabolism (Figure S13B,C).…”

“…In situ tumors in animals better simulate the TME in the organism . To further validate the sensitivity of the probe IR-ABS in detecting NTR in a real lung cancer model, we selected A549 cells with luciferase across the intercostal space of mice and inoculated them directly into the lung, forming a tumor-in situ model of the lung for about 2 weeks (Figure A).…”

“…In situ tumors in animals better simulate the TME in the organism. 55 To further validate the sensitivity of the probe IR-ABS in detecting NTR in a real lung cancer model, we selected A549 cells with luciferase across the intercostal space of mice and inoculated them directly into the lung, forming a tumor-in situ model of the lung for about 2 weeks (Figure 6A). To determine the appropriate dose for tracheal inhalation administration, we tried different volumes of the drug solution and compared the imaging area with the bioluminescence fraction.…”

An ultra pH-responsive peptide nanocarrier for cancer gene therapy

“…Once stimulated externally, the peptide will undergo chemical or physical changes, thus accurately identifying the site of the lesion, achieving its targeted delivery and precise release function, and reducing the toxic side effects on normal tissues. Common stimulus responses include enzyme, [22][23][24] pH, [25][26][27][28][29] and glutathione (GSH) [30][31][32] and so forth, with pH response being the most prominent strategy. Compared with the neutral environment of normal tissue (pH 7.4), the hypoxic microenvironment inside the solid tumor promotes the tumor to produce a large amount of lactic acid through glycolysis, thus making the tumor microenvironment slightly acidic, with a pH value of about 6.5-6.8.…”

Engineering Nanosensitizer to Remodel the TME for Hypoimmunogenic “Cold”–“Hot” Tumor Transformations

“…An ideal pore size is considered to be a key factor for the drug-loading capacity of mesoporous spheres. To assess the drug-loading ability of MTNP tK @LST-PEI, we performed nitrogen adsorption experiments to determine the pore size distribution on the surface of MTNP, MTNP-tK, and MTNP tK @LST-PEI, , and the drug loading rate and entrapment efficiency were detected by high-performance liquid chromatography (HPLC) (Figure S6, Supporting Information). , Figure i shows that the N 2 absorption/desorption isotherms of MTNP, MTNP-tK, and MTNP tK @LST-PEI. MTNP exhibited a surface area of 101.4 m 2 /g and an average pore size of 2.8 nm (Figure S7, Supporting Information), which is conducive to the effective adsorption of small drug molecules into the mesopores.…”