Biomimetic Copper-Doped Polypyrrole Nanoparticles for Enhanced Cancer Low-Temperature Photothermal Therapy.

Introduction: Photothermal therapy (PTT) has a significant potential for its application in precision tumour therapy. However, PTT-induced hyperthermia may damage healthy tissues and trigger the expression of heat shock proteins (HSPs), thereby compromising the long-term therapeutic efficacy of PTT. Methods: In this study, a biomimetic drug delivery system comprising CuP nanozymes as the inner core and platelet membrane (PM) as the outer shell was successfully developed for administering synergistic chemodynamic therapy and mild PTT. PM is encapsulated on CuP to form this biomimetic nanoparticle (PM-coated CuP nanoparticles, PC). PC possesses peroxidase (POD) activity, can facilitate the conversion of hydrogen peroxide into ·OH, thereby inhibiting the expression of HSPs. Results: Upon exposure to low-power laser irradiation (0.5 W/cm2, 1064 nm), PC can convert near-infrared II laser energy into heat energy, thereby enabling the administration of enhanced mild PTT. In vitro and in vivo experiments have demonstrated that this synergistic approach can induce over 90% tumour eradication with favourable biocompatibility. Discussion: PC exhibits high efficacy and biocompatibility, making it a promising candidate for future applications.

A Platelet-Mimicking Single-Atom Nanozyme for Mitochondrial Damage-Mediated Mild-Temperature Photothermal Therapy.

Single-atom nanozyme (SAzyme) systems have shown great potential in tumor therapy. A multifunctional SAzyme not only possesses high catalytic activity but also can be used as photothermal agents in photothermal therapy (PTT). Furthermore, it is also imperative to overcome tumor thermal resistance in SAzyme-based PTT so that PTT under a mild temperature is achievable. Herein, a novel platelet membrane (PM)-coated mesoporous Fe single-atom nanozyme (Fe-SAzyme) was formulated to solve these issues. The PM-coated mesoporous Fe-SAzyme (PMS) showed a satisfactory NIR-II photothermal performance, high peroxidase (POD) activity, and good tumor-targeting ability. In addition, PMS may be used as a carrier for protein drugs owing to its inner mesoporous structure. In vitro experiments showed that PMS could inhibit the expression of heat shock protein (HSP) by damaging the mitochondria, thereby finally improving the effect of mild-temperature PTT. Moreover, in vivo results showed that PMS could efficiently accumulate in tumor sites and suppress tumor growth with minimal toxicity in major organs. To the best of our knowledge, this study is the first report of a biomimetic mesoporous Fe-SAzyme used to achieve mitochondrial damage-mediated mild-temperature PTT. The study provides new promising ideas for designing other SAzyme systems for cancer treatment.

Delivery of manganese carbonyl to the tumor microenvironment using Tumor-Derived exosomes for cancer gas therapy and low dose radiotherapy.

The development of novel radiosensitizer with high selectivity and controllability is highly desirable. CO gas could cause damage to mitochondria and thus enhance RT effect. Controlled delivery of CO in tumor is important both to achieve high-efficiency of CO gas therapy and to decrease the risk of CO poisoning. In this study, manganese carbonyl (MnCO) loaded exosome nano-vesicles (MMV) to overcome this conundrum for tumor therapy is developed. After administration, MMV showed its admirable performance in active tumor-targeting, mitochondria damage and radiosensitization therapy. These MMV nanoparticles were able to facilitate robust CO evolution and consequent ROS generation in response to X-ray irradiation both in vitro and in vivo. Significantly, MMV could facilitate a 90% inhibition effect of tumor growth under very low dose (only 2Gy) RT, which is better than high dose (6Gy) radiotherapy. Overall, this study highlights a novel and practical approach to enhancing the efficacy of tumor RT, underscoring the value of future research in the field of CO medicine.

Novel Engineered Bacterium/Black Phosphorus Quantum Dot Hybrid System for Hypoxic Tumor Targeting and Efficient Photodynamic Therapy.

Intratumoral hypoxia significantly constrains the susceptibility of solid tumors to oxygen-dependent photodynamic therapy (PDT), and effort to reverse such hypoxia has achieved limited success to date. Herein, we developed a novel engineered bacterial system capable of targeting hypoxic tumor tissues and efficiently mediating the photodynamic treatment of these tumors. For this system, we genetically engineered Escherichia coli to express catalase, after which we explored an electrostatic adsorption approach to link black phosphorus quantum dots (BPQDs) to the surface of these bacteria, thereby generating an engineered E. coli/BPQDs (EB) system. Following intravenous injection, EB was able to target hypoxic tumor tissues. Subsequent 660 nm laser irradiation drove EB to generate reactive oxygen species (ROS) and destroy the membranes of these bacteria, leading to the release of catalase that subsequently degrades hydrogen peroxide to yield oxygen. Increased oxygen levels alleviate intratumoral hypoxia, thereby enhancing BPQD-mediated photodynamic therapy. This system was able to efficiently kill tumor cells in vivo, exhibiting good therapeutic efficacy. In summary, this study is the first to report the utilization of engineered bacteria to facilitate PDT, and our results highlight new avenues for BPQD-mediated cancer treatment.

Injectable Hydrogel for NIR-II Photo-Thermal Tumor Therapy and Dihydroartemisinin-Mediated Chemodynamic Therapy.

In traditional Chinese medicine, dihydroartemisinin (DHA) is the focus of extensive attention because of its unique activity with Fe2+ to produce reactive oxygen species (ROS) and promote apoptosis. In this work, we designed a newfangled ink@hydrogel containing FeCl3, traditional Chinese ink (Hu Kaiwen ink), and agarose hydrogel to create a synergistic activity with DHA in the treatment of cancer. When the system is irradiated under 1,064 nm for a few minutes, the ink in the ink@hydrogel converts the light to heat and hyperthermia causes the reversible hydrolysis of hydrogel. Then, Fe3+ quickly diffuses from the hydrogel to the tumor microenvironment and is reduced to Fe2+ to break the endoperoxide bridge in pre-injected DHA, which results in the release of free radicals for a potent anticancer action. To our knowledge, this is the first report of a hydrogel tumor therapy system that induces a photo-thermal response in the second near infrared window (NIR-II). in vivo experiments also showed a significant effect of DHA-Fe2+ in chemodynamic therapy (CDT) and in photo-thermal therapy. This hydrogel platform provided an encouraging idea for synergistic tumor therapy.