In the absence of adequate oxygen, cancer cells that are grown in hypoxic solid tumors resist treatment using antitumor drugs (such as doxorubicin, DOX), owing to their attenuated intracellular production of reactive oxygen species (ROS). Hyperbaric oxygen (HBO) therapy favorably improves oxygen transport to the hypoxic tumor tissues, thereby increasing the sensitivity of tumor cells to DOX. However, the use of HBO with DOX potentiates the ROS-mediated cytotoxicity of the drug toward normal tissues. In this work, we hypothesize that regional oxygen treatment by an implanted oxygen-generating depot may enhance the cytotoxicity of DOX against malignant tissues in a highly site-specific manner, without raising systemic oxygen levels. Upon implantation close to the tumor, the oxygen-generating depot reacts with the interstitial medium to produce oxygen in situ, effectively shrinking the hypoxic regions in the tumor tissues. Increasing the local availability of oxygen causes the cytotoxicity of DOX that is accumulated in the tumors to be significantly enhanced by the elevated production of ROS, ultimately allaying the hypoxia-induced DOX resistance in solid malignancies. Importantly, this enhancement of cytotoxicity is limited to the site of the tumors, and this feature of the system that is proposed herein is unique.

No abstract

Alternative approaches to treating subcutaneous abscesses—especially those associated with antibiotic‐resistant pathogenic bacterial strains—that eliminate the need for antibiotics are urgently needed. This work descibes a chitosan (CS) derivative with self‐doped polyaniline (PANI) side chains that can self‐assemble into micelles in an aqueous environment and be transformed into colloidal gels in a process that is driven by a local increase in pH. These self‐doped PANI micelles can be utilized as nano‐localized heat sources, remotely controllable using near‐infrared (NIR) light. To test the in vivo efficacy of the CS derivative as a photothermal agent, an aqueous solution thereof is directly injected at the site of infected abscesses in a mouse model. The injected polymer solution eventually becomes distributed over the acidic abscesses, forming colloidal gels when it meets the boundaries of healthy tissues. After treatment with an 808 nm laser, the colloidal gels convert NIR light into heat, causing the thermal lysis of bacteria and repairing the infected wound without leaving residual implanted materials. This approach has marked potential because it can provide colloidal gels with tunable spatial stability, limiting localized heating to the infected sites, and reducing thermal damage to the surrounding healthy tissues.

No abstract

No abstract