NIR-II-triggered doxorubicin release for orthotopic bladder cancer chemo-photothermal therapy.

Intravesical instillation has been widely utilized for bladder cancer treatment in clinic. However, due to the bladder mucosal barrier, its poor penetration efficiency and drug utilization limit the clinical therapeutic effectiveness and result in a high recurrence rate. Therefore, designing an efficient and controllable drug delivery nanoplatform is of great significance for bladder cancer treatment. Non-invasive therapy based on near-infrared-II (NIR-II) photothermal therapy (PTT) conduces to overcome bladder mucosal barrier and enhance drug delivery. Also, the photothermal nanomaterials, Au Hollow Nanorods (AuHNRs), demonstrate strong photothermal properties and drug loading capacity. Herein, a quaternized chitosan N-(2-hydroxyl)propyl-3-trimethyl ammonium chitosan chloride (HTCC)-modified nanocarrier Dox/NH4HCO3@AuHNRs-HTCC (DNAH) was designed for controlled drug release and enhanced penetration. The drug loading capacity of DNAH reached 117.20%. Also, the thermal decomposition of NH4HCO3 realized NIR-II-triggered gas-driven drug burst release, and the doxorubicin release was 2.79 times higher within 1 h after NIR-II irradiation. Also, the HTCC-modified nanocarriers significantly enhanced the bladder mucosal permeability as well as long-term drug retention, and the penetration efficiency of DNAH increased by 144%. In the orthotopic bladder cancer model, the tumor suppression rate and mouse survival time were significantly improved. DNAH showed potent inhibition of the orthotopic bladder tumor growth owing to the enhanced penetration and drug delivery. This work presents a potential drug delivery nanocarrier, which is promising for optimized bladder mucosal permeability and controlled drug burst release.

Near-Infrared-II Activatable Symbiotic 2D Carbon-Clay Nanohybrids for Dual Imaging-Guided Combinational Cancer Therapy.

Two-dimensional (2D) nanomaterials hold great potential for cancer theranostic applications, yet their clinical translation faces great challenges of high toxicity and limited therapeutic/diagnostic modality. Here, we have created a kind of symbiotic 2D carbon-2D clay nanohybrids, which are composed of a novel 2D carbon nanomaterial (carbon nanochips, or CNC), prepared by carbonizing a conjugated polymer polydiiodobutadiyne, and a 2D layered aluminosilicate clay mineral montmorillonite (MMT). Intriguingly, with the formation of the nanohybrids, MMT can help the dispersion of CNC, while CNC can significantly reduce the hemolysis and toxicity of MMT. The symbiotic combination of CNC and MMT also leads to a synergistic anti-cancer theranostic effect. CNC has a strong absorption and high photothermal conversion efficiency in the second near-infrared region (NIR-II, 1000-1700 nm), while MMT contains Fe3+ that can facilitate the generation of reactive oxygen species from highly expressed H2O2 in tumor microenvironment. The nanohybrids not only enable a synergy of photothermal therapy and chemodynamic therapy to suppress the extremely rapid growth of RM1 tumors in mice but also allow for dual photoacoustic and magnetic imaging to guide the drug delivery and NIR-II irradiation execution, hence establishing a highly efficient and biosafe "all-in-one" theranostic platform for precision nanomedicine.

Biologically Safe, Versatile, and Smart Bismuthene Functionalized with a Drug Delivery System Based on Red Phosphorus Quantum Dots for Cancer Theranostics.

Two-dimensional nanomaterials are attracting attention for cancer therapy. However, high toxicity, insensitivity to external stimuli and single therapeutic modality are still key issues hindering their clinical application. Therefore, the construction of a safe, intelligent and versatile nanocomposite is needed to meet clinical expectations. Herein, we developed a nanocomposite of Bi@RP-PEG-DOX with 2D bismuthene loaded with 0D red phosphorus quantum dots and DOX. The nanocomposite with DOX loading capacity (ca. 250 %) and photothermal conversion efficiency (ca. 54 %) showed both photothermal and photodynamic effects and a sensitive response of drug release to the acidic tumor microenvironment or NIR II laser irradiation. The nanocomposite exhibits good biosafety. Through the X-ray attenuation properties of bismuth, the nanocomposite serves as an excellent CT contrast agent, providing potential to perform CT-guided therapy.

Vitamin K2 promotes PI3K/AKT/HIF-1α-mediated glycolysis that leads to AMPK-dependent autophagic cell death in bladder cancer cells.

Vitamin K2 has been shown to exert remarkable anticancer activity. However, the detailed mechanism remains unclear. Here, our study was the first to show that Vitamin K2 significantly promoted the glycolysis in bladder cancer cells by upregulating glucose consumption and lactate production, whereas inhibited TCA cycle by reducing the amounts of Acetyl-CoA. Moreover, suppression of PI3K/AKT and HIF-1α attenuated Vitamin K2-increased glucose consumption and lactate generation, indicating that Vitamin K2 promotes PI3K/AKT and HIF-1α-mediated glycolysis in bladder cancer cells. Importantly, upon glucose limitation, Vitamin K2-upregulated glycolysis markedly induced metabolic stress, along with AMPK activation and mTORC1 pathway suppression, which subsequently triggered AMPK-dependent autophagic cell death. Intriguingly, glucose supplementation profoundly abrogated AMPK activation and rescued bladder cancer cells from Vitamin K2-triggered autophagic cell death. Furthermore, both inhibition of PI3K/AKT/HIF-1α and attenuation of glycolysis significantly blocked Vitamin K2-induced AMPK activation and subsequently prevented autophagic cell death. Collectively, these findings reveal that Vitamin K2 could induce metabolic stress and trigger AMPK-dependent autophagic cell death in bladder cancer cells by PI3K/AKT/HIF-1α-mediated glycolysis promotion.