External Catalyst- and Additive-Free Photo-Oxidation of Aromatic Alcohols to Carboxylic Acids or Ketones Using Air/O2.

We present an environment-friendly and highly efficient method for the oxidation of aromatic alcohols to carboxylic acids or ketones in air via light irradiation under external catalyst-, additive-, and base-free conditions. The photoreaction system exhibits a wide substrate scope and the potential for large-scale applications. Most of the desired products are easily obtained via recrystallization and separation from low-boiling reaction medium acetone in good yields, and the products can be subsequent directly transformed without further purification.

Prodrug Nanosensitizer Overcomes the Radiation Resistance of Hypoxic Tumor.

Clinical radiation therapy (RT) is often hindered by the low radiation energy absorption coefficient and the hypoxic features of tumor tissues. Among the tremendous efforts devoted to overcoming the barriers to efficient RT, the application of hypoxic radiosensitizers and cell-cycle-specific chemotherapeutics has shown great potential. However, their effectiveness is often compromised by their limited bioavailability, especially in the hypoxic region, which plays a major role in radioresistance. Herein, to simultaneously improve the delivery efficacy of both hypoxic radiosensitizer and cell-cycle-specific drug, a gambogic acid (GA) metronidazole (MN) prodrug (GM) was designed and synthesized based on GA, a naturally occurring chemotherapeutic and multiple pathway inhibitor, and MN, a typical hypoxic radiosensitizer. In combination with MN-containing block copolymers, the prodrug nanosensitizer (NS) of GM was obtained. Owing to the bioreduction of MN, the as-designed prodrug could be efficiently delivered to hypoxic cells and act on mitochondria to cause the accumulation of reactive oxygen species. The strong G2/M phase arrest caused by the prodrug NS could further sensitize treated cells to external radiation under hypoxic conditions by increasing DNA damage and delaying DNA repair. After coadministration of the NS with a well-established tissue-penetrating peptide, efficient tumor accumulation, deep tumor penetration, and highly potent chemoradiotherapy could be achieved.

Reduction-sensitive platinum (IV)-prodrug nano-sensitizer with an ultra-high drug loading for efficient chemo-radiotherapy of Pt-resistant cervical cancer in vivo.

Cisplatin is widely used in the chemoradiotherapy (CRT) of cervical cancers. However, despite the severe systemic side effects, the therapeutic efficacy of cisplatin is often compromised by the development of drug resistance, which is closely related to the elevated intracellular thiol-containing species (especially glutathione (GSH)) and the adenosine triphosphate (ATP)-dependent glutathione S-conjugate pumps. The construction of a safe and redox-sensitive nano-sensitizer with high disulfide density and high Pt(IV) prodrug loading capacity (up to 16.50% Pt and even higher), as described herein, is a promising way to overcome the cisplatin resistance and enhance the CRT efficacy. The optimized nanoparticles (NPs) (referred to as SSCV5) with moderate Pt loading (7.62% Pt) and median size (c.a. 40 nm) was screened out and used for further biological evaluation. Compared with free cisplatin, more drugs could be transported and released inside the cisplatin resistant cells (Hela-CDDP) by SSCV5 NPs. With the synergistic effect of GSH scavenging and mitochondrial damage, SSCV5 NPs can easily reverse the cisplatin resistance. Moreover, the higher nucleus DNA binding Pt content of SSCV5 NPs not only caused the DNA damage and apoptosis of Hela-CDDP cells but also sensitized these cells to X-Ray radiation. The in vivo safety and efficacy results showed that SSCV5 NPs effectively accumulated inside tumor and inhibited the growth of cisplatin resistant xenograft models while alleviating the serious side effect associated with cisplatin (the maximum tolerated cisplatin equivalent of single injection is higher than 20 mg/kg body weight). The intervention of exogenous radiation further improved the anticancer efficacy of SSCV5 NPs and caused the shrinkage of tumor volume, thus making this safe and facile nano-sensitizer a promising route for the neoadjuvant CRT of cervical cancers.

Mucoadhesive nanoparticles based on ROS activated gambogic acid prodrug for safe and efficient intravesical instillation chemotherapy of bladder cancer.

Chemotherapy is the standard of care for bladder cancer after transurethral resection of the tumor. However, the rapid excretion of clinically used formulations of anticancer drugs make the common intravesical instillation chemotherapy far from efficient. Therefore, improving the muco-adhesion and penetrability of chemotherapeutic drugs became the key factors in the post-surgery treatment of superficial bladder cancers. Here, a reduction sensitive vehicle was developed to deliver the reactive oxygen species activated prodrug of gambogic acid for treatment of orthotopic bladder cancer. The positively charged chitosan can significantly enhance the adhesion and permeability of prodrug within the bladder wall. Moreover, by utilizing the different glutathione and ROS level between cancer cells and normal cells, the dual responsive nanoparticle can selectively and rapidly deliver drug in bladder cancer cells, and thus can significantly inhibit the proliferation of bladder cancer cells in an orthotopic superficial bladder cancer model without causing damage to normal cells. This work demonstrates that the smart prodrug nanomedicine may act as a promising drug-delivery system for local chemotherapy of bladder cancer with unprecedented clinical benefits.