Even though cancer treatment has improved over the recent decades, still more specific and effective treatment concepts are mandatory. Surgical removal is not always possible, metastases are challenging and chemo- and radiotherapy can not only have severe side-effects but also resistances may occur. To cope with these challenges more efficient therapies with fewer side-effects are required. One promising approach is the use of drug delivery vehicles. Here, mesoporous silica nanoparticles (MSN) are discussed as biodegradable drug carrier to improve efficacy and reduce side-effects. MSN excellently fulfill the criteria for nanoparticulate carriers: their distinct structure allows high loading capacity and a plethora of surface modifications. MSN synthesis permits fine-tuning of particle and pore sizes. Moreover, drug release can be tailored through various gatekeeper systems which are for example pH-sensitive or redox-sensitive. Furthermore, MSN can either enter tumors passively by the enhanced permeability and retention effect or can be actively targeted by various ligands. PEGylation prolongs circulation time and availability. A huge advantage of MSN is their explicitly low toxic profile in vivo. Yet, clinical translation remains challenging. Overall, mesoporous silica nanoparticles are a promising tool for innovative, more efficient and safer cancer therapies.

Due to the demographic change, medicine faces a growing demand for tissue engineering solutions and implants. Often, satisfying tissue regeneration is difficult to achieve especially when co-morbidities hamper the healing process. As a novel strategy, we propose the incorporation of zinc oxide nanoparticles (ZnO NPs) into biomaterials to improve tissue regeneration. Due to their wide range of biocompatibility and their antibacterial properties, ZnO NPs are already discussed for different medical applications. As there are versatile possibilities of modifying their form, size, and function, they are becoming increasingly attractive for tissue engineering. In our study, in addition to antibacterial effects of ZnO NPs, we show for the first time that ZnO NPs can foster the metabolic activity of fibroblasts as well as endothelial cells, both cell types being crucial for successful implant integration. With the gelatin sponge method performed on the chicken embryo’s chorioallantoic membrane (CAM), we furthermore confirmed the high biocompatibility of ZnO NPs. In summary, we found ZnO NPs to have very favorable properties for the modification of biomaterials. Here, incorporation of ZnO NPs could help to guide the tissue reaction and promote complication-free healing.

Nanomaterials unveil many applicational possibilities for technical and medical purposes, which range from imaging techniques to the use as drug carriers. Prior to any human application, analysis of undesired effects and characterization of their toxicological profile is mandatory. To address this topic, animal models, and rodent models in particular, are most frequently used. However, as the reproducibility and transferability to the human organism of animal experimental data is increasingly questioned and the awareness of animal welfare in society increases at the same time, methodological alternatives are urgently required. The chorioallantoic membrane (CAM) assay is an increasingly popular in ovo experimental organism suitable for replacement of rodent experimentation. In this review, we outline several application fields for the CAM assay in the field of nanotoxicology. Furthermore, analytical methods applicable with this model were evaluated in detail. We further discuss ethical, financial, and bureaucratic aspects and benchmark the assay with other established in vivo models such as rodents.

The effective management of tissue integration and immunological responses to transplants decisively co-determines the success of soft and hard tissue reconstruction. The aim of this in vivo study was to evaluate the eligibility of extracorporeal shock wave therapy (ESWT) with respect to its ability to modulate angiogenesis and immune response to a collagen matrix (CM) for tissue engineering in the chorioallantoic membrane (CAM) assay, which is performed with fertilized chicken eggs. CM were placed on the CAM on embryonic development day (EDD) 7; at EDD-10, ESWT was conducted at 0.12 mJ/mm² with 500 impulses each. One and four days later, angiogenesis represented by vascularized area, vessel density, and vessel junctions as well as HIF-1α and VEGF gene expression were evaluated. Furthermore, immune response (iNOS2, MMP-9, and MMP-13 via qPCR) was assessed and compared between ESWT- and non-ESWT-groups. At EDD-14, the vascularized area (+115% vs. +26%) and the increase in vessel junctions (+751% vs. +363%) were significantly higher in the ESWT-group. ESWT significantly increased MMP-9 gene expression at EDD-11 and significantly decreased MMP-13 gene expression at EDD-14 as compared to the controls. Using the CAM assay, an enhanced angiogenesis and neovascularization in CM after ESWT were observed. Furthermore, ESWT could reduce the inflammatory activity after a latency of four days.

Despite recent advancements in tumor therapy, metastasis and tumor relapse remain major complications hindering the complete recovery of many cancer patients. Dormant tumor cells, which reside in the body, possess the ability to re-enter the cell cycle after therapy. This phenomenon has been attributed to therapy-induced senescence. We show that these cells could be targeted by the use of zinc oxide nanoparticles (ZnO NPs). In the present study, the properties of tumor cells after survival of 16 Gy gamma-irradiation were investigated in detail. Analysis of morphological features, proliferation, cell cycle distribution, and protein expression revealed classical hallmarks of senescent cells among the remnant cell mass after irradiation. The observed radiation-induced senescence was associated with the increased ability to withstand further irradiation. Additionally, tumor cells were able to re-enter the cell cycle and proliferate again after weeks. Treatment with ZnO NPs was evaluated as a therapeutical approach to target senescent cells. ZnO NPs were suitable to induce cell death in senescent, irradiation-resistant tumor cells. Our findings underline the pathophysiological relevance of remnant tumor cells that survived first-line radiotherapy. Additionally, we highlight the therapeutic potential of ZnO NPs for targeting senescent tumor cells.