DHTPY-Cu@ZOL-Enhanced Photodynamic Therapy: A Strategic Platform for Advanced Treatment of Drug-Resistant Bacterial Wound Infections.

Purpose: This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation. Methods: Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme's size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA). Results: The DHTPY-Cu@ZOL exhibited proficient H2O2 scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes' potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections. Conclusion: Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.

Expanded ROS Generation and Hypoxia Reversal: Excipient-free Self-assembled Nanotheranostics for Enhanced Cancer Photodynamic Immunotherapy.

The efficacy of photodynamic therapy (PDT)-related cancer therapies is significantly restricted by two irreconcilable obstacles, i.e., low reactive oxygen species (ROS) generation capability and hypoxia which constrains the immune response. Herein, this work develops a self-assembled clinical photosensitizer indocyanine green (ICG) and the HSP90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) nanoparticles (ISDN) without any excipient. This work discovers that the hydrophobic interaction forces between ICG and 17-DMAG promote the photostability of ICG and its intersystem crossing (ISC) process, thereby improving the ROS quantum yield from 0.112 to 0.46. Augmented ROS generation enhances PDT efficacy and further enhances immunogenic cell death (ICD) effects. 17-DMAG inhibits the HSP90/hypoxia-inducible factor 1α (HIF-1α) axis to dramatically reverse the immunosuppressive tumor microenvironment caused by PDT-aggravated hypoxia. In a mouse model of pancreatic cancer, ISDN markedly improve cytotoxic T lymphocyte infiltration and MHC I and MHC II activation, demonstrating the superior ICD effects in situ tumor and the powerful systematic antitumor immunity generation, eventually achieving vigorous antitumor and recurrence resistance. This study proposes an unsophisticated and versatile strategy to significantly improve PDT efficacy for enhancing systemic antitumor immunity and potentially extending it to multiple cancers.

Stimulus-Responsive Zwitterionic Prodrug Delivery System with Sustained Release of Hydrogen Sulfide for Protective Aortic Dissection.

Aortic dissection (AD) is one of the most frequent types of aortic disease with extremely poor prognosis. The biological signaling gas hydrogen sulfide (H2S) has exhibited protective effects in various types of cardiovascular diseases. However, as a toxic, colorless gas, the application of H2S is immensely hampered due to the lack of ideal donors. In this article, a drug delivery system with a H2S donor has been prepared. Meanwhile, the donor could be deposed in a cysteine-containing environment to generate H2S. The results indicate that the H2S donor polymer nanomicelles mitigated the processive transformation of smooth muscle cells effectively in a proper concentration range, which may play a protective role in aortic dissection. In animal experiments, the sustained-release H2S donor stimulated in the presence of cysteine was found to demonstrate beneficial effects in a murine model of aortic dissection and would likely become a potential target of H2S therapy for cardiovascular diseases.

White light-triggered zwitterionic polymer nanoparticles based on an AIE-active photosensitizer for photodynamic antimicrobial therapy.

Photodynamic antimicrobial therapy (PDAT) has received enormous attention due to its excellent spatiotemporal accuracy, non-invasiveness, and anti-multidrug resistance properties compared with chemotherapy. However, traditional PDAT methods possess numerous disadvantages, such as high dark toxicity, poor chemical stability, susceptibility to fluorescence quenching, and relatively low ROS efficiency in water. In this work, we successfully fabricated a type of pH-responsive zwitterionic polyurethane nano-micelle possessing great reactive oxygen species (ROS) generation efficiency due to the smaller singlet-triplet energy gap of its AIE PS moiety. This nano-system also has near-infrared bioimaging functionality, and can detect bacteria in real time. In addition, the hydrophilic zwitterionic polyurethanes plays a vital role in antifouling, enhancing biocompatibility and prolonging circulation time under normal conditions (pH 7.4). Under acidic conditions (pH 5.4), the zwitterionic moiety is suddenly protonated to enable positively charged nano-micelles to target the bacterial infection site, resulting in great antibacterial efficiency, which is superior to the existing PDAT method.