ExoDS: a versatile exosome-based drug delivery platform to target cancer cells and cancer stem cells

Chemotherapy drugs like doxorubicin (Dox) are widely used in middle-income countries around the world to treat various types of cancers, including breast cancer. Although they are toxic, they are still widely used to treat cancer. Delivering chemotherapy drugs directly to cancer cells to reduce side effects remains a challenge. Moreover, modern research gave rise to cancer stem cell theory, which implicated cancer stem cells in tumor initiation, progression, and relapse. This makes it imperative to target cancer stem cells to achieve complete remission. Our work highlights the development of an exosome-based targeted drug delivery vehicle. These exosomes were isolated from mature dendritic cells (mDCs) and encapsulated with doxorubicin (ExoDS). Our results showed that ExoDS specifically targeted breast cancer cells and breast cancer stem cells. Further analysis revealed that ExoDS did not induce any significant apoptosis in healthy mammary cells and peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals and breast cancer patients. ExoDS was also found to target circulating tumor cells (CTCs) isolated from patient blood. ExoDS also showed equal efficiency compared to free doxorubicin in vivo. We also observed that ExoDS reduced the expression of cancer stem cell markers in murine tumor tissues. Altogether, this work provides novel insights into how mDC-derived exosomes can be used to specifically target cancer cells and cancer stem cells

Neutrophils in Cancer and Potential Therapeutic Strategies Using Neutrophil-Derived Exosomes

Neutrophils are the most abundant immune cells and make up about 70% of white blood cells in human blood and play a critical role as the first line of defense in the innate immune response. They also help regulate the inflammatory environment to promote tissue repair. However, in cancer, neutrophils can be manipulated by tumors to either promote or hinder tumor growth depending on the cytokine pool. Studies have shown that tumor-bearing mice have increased levels of neutrophils in peripheral circulation and that neutrophil-derived exosomes can deliver various cargos, including lncRNA and miRNA, which contribute to tumor growth and degradation of extracellular matrix. Exosomes derived from immune cells generally possess anti-tumor activities and induce tumor-cell apoptosis by delivering cytotoxic proteins, ROS generation, H2O2 or activation of Fas-mediated apoptosis in target cells. Engineered exosome-like nanovesicles have been developed to deliver chemotherapeutic drugs precisely to tumor cells. However, tumor-derived exosomes can aggravate cancer-associated thrombosis through the formation of neutrophil extracellular traps. Despite the advancements in neutrophil-related research, a detailed understanding of tumor-neutrophil crosstalk is still lacking and remains a major barrier in developing neutrophil-based or targeted therapy. This review will focus on the communication pathways between tumors and neutrophils, and the role of neutrophil-derived exosomes (NDEs) in tumor growth. Additionally, potential strategies to manipulate NDEs for therapeutic purposes will be discussed

Feasibility of HPV self-sampling pathway in Kathmandu Valley, Nepal using a human-centred design approach

Cervical cancer is preventable and curable yet causes almost 2000 deaths in Nepali women each year. The present study aims to explore the feasibility and acceptability of a self-sampling-based approach for cervical cancer screening in urban and peri-urban Nepal and develop pathways for self-sampling using a co-design methodology. An iterative design approach was applied. Semi-structured in-depth interviews were conducted with 30 healthy women and four women who had had a prior cancer diagnosis on topics which included: sexual and reproductive health knowledge and human papillomavirus (HPV); use of the internet/social media platforms; their views regarding acceptability and usability of the self-sampling kit and the proposed user journey. Data collection was done between December 2020 and January 2021. Seven medical experts were also interviewed to explore the current service configuration for cervical cancer screening in Nepal. Knowledge regarding HPV and its association with cervical cancer was absent for the majority of participants. Although 70% (n = 21/30) had purchased items online previously, there was a general lack of trust in online shopping. Half of the women (n = 17/30; 56.7%) expressed a willingness to self-sample and provided recommendations to improve the clarity of the instructions. The proposed user journey was considered feasible in the urban area. There is a clear unmet need for information about HPV and alternative cervical screening options in Nepal. An online pathway for self-sampling service delivery to urban women is feasible but will need to be optimally designed to address barriers such as confidence in self-sampling and trust in online purchasing

Corrigendum: Near-Single-Cell Proteomics Profiling of the Proximal Tubular and Glomerulus of the Normal Human Kidney.

[This corrects the article DOI: 10.3389/fmed.2020.00499.]

Near-Single-Cell Proteomics Profiling of the Proximal Tubular and Glomerulus of the Normal Human Kidney.

Molecular assessments at the single cell level can accelerate biological research by providing detailed assessments of cellular organization and tissue heterogeneity in both disease and health. The human kidney has complex multi-cellular states with varying functionality, much of which can now be completely harnessed with recent technological advances in tissue proteomics at a near single-cell level. We discuss the foundational steps in the first application of this mass spectrometry (MS) based proteomics method for analysis of sub-sections of the normal human kidney, as part of the Kidney Precision Medicine Project (KPMP). Using ~30-40 laser captured micro-dissected kidney cells, we identified more than 2,500 human proteins, with specificity to the proximal tubular (PT; n = 25 proteins) and glomerular (Glom; n = 67 proteins) regions of the kidney and their unique metabolic functions. This pilot study provides the roadmap for application of our near-single-cell proteomics workflow for analysis of other renal micro-compartments, on a larger scale, to unravel perturbations of renal sub-cellular function in the normal kidney as well as different etiologies of acute and chronic kidney disease

Corrigendum: Near-Single-Cell Proteomics Profiling of the Proximal Tubular and Glomerulus of the Normal Human Kidney.

[This corrects the article DOI: 10.3389/fmed.2020.00499.]