Engineering cannabidiol synergistic carbon monoxide nanocomplexes to enhance cancer therapy via excessive autophagy

Although carbon monoxide(CO)-based treatments have demonstrated the high cancer efficacy by promoting mitochondrial damage and core-region penetrating ability,the efficiency was often compromised by protective autophagy(mitophagy).Herein,cannabidiol(CBD)is integrated into biomimetic carbon monoxide nanocomplexes(HMPOC@M)to address this issue by inducing excessive autophagy.The biomimetic membrane not only prevents premature drugs leakage,but also prolongs blood circulation for tumor enrichment.After entering the acidic tumor microenvironment,carbon monoxide(CO)donors are stimulated by hydrogen oxide(H_(2)O_(2))to disintegrate into CO and Mn^(2+).The comprehensive effect of CO/Mn^(2+)and CBD can induce ROS-mediated cell apoptosis.In addition,HMPOC@Mmediated excessive autophagy can promote cancer cell death by increasing autophagic flux via classⅢPI3K/BECN1 complex activation and blocking autolysosome degradation via LAMP1 downregulation.Furthermore,in vivo experiments showed that HMPOC@M+laser strongly inhibited tumor growth and attenuated liver and lung metastases by downregulating VEGF and MMP9 proteins.This strategy may highlight the pro-death role of excessive autophagy in TNBC treatment,providing a novel yet versatile avenue to enhance the efficacy of CO treatments.Importantly,this work also indicated the applicability of CBD for triple-negative breast cancer(TNBC)therapy through excessive autophagy.

Clinical Application and Prospect of New Radiotherapy Technology in Cancer Treatment

Objective: Carbon ion therapy, a new radiotherapy technology, has shown its remarkable efficacy and potential in cancer treatment, especially in the treatment of refractory tumors. Methods: This paper clarifies the physical basis, technological change, and clinical practice effect of carbon ion therapy, comprehensively discusses the future prospects, and evaluates the clinical application effect. Results: The technology has significantly improved the treatment effectiveness and received a positive response from patients. Conclusion: Carbon ion therapy technology has become a major innovation in the field of cancer treatment. It not only has a profound impact on many current cancer therapy methods but also indicates the application blueprint for a wider range of cancer types in the future, showing a new chapter of medical technology advancement.

Highly efficient gene silencing and bioimaging based on fluorescent carbon dots in vitro and in vivo

Small interfering RNA （siRNA） is an attractive therapeutic candidate for sequence- specific gene silencing to treat incurable diseases using small molecule drugs. However, its efficient intracellular delivery has remained a challenge. Here, we have developed a highly biocompatible fluorescent carbon dot （CD）, and demonstrate a functional siRNA delivery system that induces efficient gene knockdown in vitro and in vivo. We found that CD nanoparticles （NPs） enhance the cellular uptake of siRNA, via endocytosis in tumor cells, with low cytotoxicity and unexpected immune responses. Real-time study of fluorescence imaging in live cells shows that CD NPs favorably localize in cytoplasm and successfully release siRNA within 12 h. Moreover, we demonstrate that CD NP-mediated siRNA delivery significantly silences green fluorescence protein （GFP） expression and inhibits tumor growth in a breast cancer cell xenograft mouse model of tumor-specific therapy. We have developed a multifunctional siRNA delivery vehicle enabling simultaneous bioimaging and efficient downregulation of gene expression, that shows excellent potential for gene therapy.

The role of radiation therapy and particle therapy in renal cell carcinoma: current evidence and future perspectives

For both primary and metastatic renal cell carcinoma(RCC),treatment with stereotactic body radiotherapy(SBRT)has found its way into clinical practice.Being a non-invasive outpatient procedure,SBRT requires only a few visits to the radiation department and may be of interest for the elderly or,in the case of primary RCC,for patients who are not considered surgical candidates due to technical limitations,medical comorbidities,or in the event that the maintenance of kidney function is compromised.In the treatment landscape of oligometastatic RCC,SBRT shows promise in eradicating metastatic disease and delaying the initiation of systemic treatment.Technical advancements in the planning and administration of radiation treatment and improvements in movement management allow irradiating the tumor and/or metastatic lesions with very high doses in few fractions while maximally sparing the surrounding organs at risk,thus minimizing toxicity.In that context,the increasing availability of particle therapy,such as proton beam radiotherapy or carbon ion radiotherapy,could further optimize the delivery of radiation treatment in order to reduce toxicity and improve outcome.

Advances in quantum dot-mediated siRNA delivery

Nano-sized quantum dots（QDs） exhibit uniquely optical properties that are tunable with different sizes and shapes.QDs can emit narrow symmetric bands under a wide excitation range,possess antiphotobleaching stability,and be bio-functionalized on the large surface area.Therefore,QDs are attractive vectors for imaging-guided therapy.Small-interfering RNA（siRNAs）-based therapeutics hold great potential to target a large part of the currently undruggable genes,but overcoming the lipid bilayer to deliver siRNA into cells has remained a major challenge to solve for widespread development of siRNA therapeutics.In this mini-review,we focus on theranostic QD/siRNA assembles for enhancing delivery of siRNA and facilitating evaluation of therapeutic efficacy via imaging of QDs,with special attention to carbonaceous QDs for delivery of siRNA.