Biomimetic nanomedicines for precise atherosclerosis theranostics

Atherosclerosis (AS) is a leading cause of the life-threatening cardiovascular disease (CVD), creating an urgent need for efficient, biocompatible therapeutics for diagnosis and treatment. Biomimetic nanomedicines (bNMs) are moving closer to fulfilling this need, pushing back the frontier of nano-based drug delivery systems design. This review seeks to outline how these nanomedicines (NMs) might work to diagnose and treat atherosclerosis, to trace the trajectory of their development to date and in the coming years, and to provide a foundation for further discussion about atherosclerotic theranostics.

Current approaches of nanomedicines in the market and various stage of clinical translation

Compared with traditional drug therapy, nanomedicines exhibit intriguing biological features to increase therapeutic efficiency, reduce toxicity and achieve targeting delivery. This review provides a snapshot of nanomedicines that have been currently launched or in the clinical trials, which manifests a diversified trend in carrier types, applied indications and mechanisms of action. From the perspective of indications, this article presents an overview of the applications of nanomedicines involving the prevention, diagnosis and treatment of various diseases, which include cancer, infections, blood disorders, cardiovascular diseases, immuno-associated diseases and nervous system diseases, etc. Moreover, the review provides some considerations and perspectives in the research and development of nanomedicines to facilitate their translations in clinic.

A framework for advanced technology medicines from the perspective of community pharmacists; with or without technology

Abstract Nowadays, the number of medicines manufactured using advanced technologies such as biotechnology, nanotechnology, and 3D printing is increasing along with the accelerated pace of technological change. Evaluating high technology medicines from the perspective of community pharmacists is important for the quality of the pharmacy practice. The aim is to analyze the knowledge, attitude, and behavior of community pharmacists regarding advanced technology medicines and to examine the social and ethical aspects from the pharmacist's perspective. A face-to-face cross-sectional survey was conducted with each of the 879 community pharmacists in Istanbul using a stratified sampling method. In this context, the gaps in pharmacists' knowledge of high technology medicines were determined. It has been found that the pharmacists' level of knowledge and willingness to learn new technologies differs according to the current education levels of the pharmacists and diversity in patient profiles. The pharmacists should close the knowledge gaps and update their information about medicines that are manufactured via the implementation of advanced technologies. The more pharmacists adapt to technology, the better guidance they can offer to society. This will also ensure that communication between the pharmacist and the patient to be built on trust, and significantly improve pharmacy practice.

Nanomedicines for the treatment of rheumatoid arthritis: State of art and potential therapeutic strategies

Increasing understanding of the pathogenesis of rheumatoid arthritis (RA) has remarkably promoted the development of effective therapeutic regimens of RA. Nevertheless, the inadequate response to current therapies in a proportion of patients, the systemic toxicity accompanied by long-term administration or distribution in non-targeted sites and the comprised efficacy caused by undesirable bioavailability, are still unsettled problems lying across the full remission of RA. So far, these existing limitations have inspired comprehensive academic researches on nanomedicines for RA treatment. A variety of versatile nanocarriers with controllable physicochemical properties, tailorable drug release pattern or active targeting ability were fabricated to enhance the drug delivery efficiency in RA treatment. This review aims to provide an up-to-date progress regarding to RA treatment using nanomedicines in the last 5 years and concisely discuss the potential application of several newly emerged therapeutic strategies such as inducing the antigen-specific tolerance, pro-resolving therapy or regulating the immunometabolism for RA treatments.

Precision Medicine, Artificial Intelligence, and Genomic Markers in Urology. Do we need to Tailor our Clinical Practice? / Medicina de precisión, inteligencia artificial y marcadores genómicos en urología. ¿Debemos cambiar nuestra práctica clínica?

Precision medicine plays a key role in urological oncology practice nowadays, with the breakthrough of the poly (ADP-ribose) polymerase inhibitors (PARPi), which play a critical role in different DNA damage repair (DDR) pathways, the immune checkpoint inhibitors, the genomic expression profiles and current genome manipulation-directed targeted therapy. Information and technology (IT) are set to change the way we assess and treat patients and should be reviewed and discussed. The aim of the present article is to demonstrate a detailed revision on precision medicine, including novel therapeutic targets, genomic markers, genomic stratification of urological patients, and the top-notch technological breakthroughs that could change our clinical practice We performed a review of the literature in four different databases (PubMed, Embase, Lilacs, and Scielo) on any information concerning prostate, bladder, kidney and urothelial cancer novel treatments with PARPi, immune checkpoint inhibitors (ICIs), targeted therapy with fibroblast growth factor receptor inhibitors (FGFRi), and theranostics with prostate-specific membrane antigen (PSMA) targeted monoclonal antibodies. Artificial intelligence, machine learning, and deep learning algorithm in urological practice were also part of the search. We included all articles written in English, published within the past 7 years, that discussed outstanding therapies and genomics in urological cancer and artificial intelligence applied to urology. Meanwhile, we excluded articles with lack of a clear methodology and written in any other language than English. One-hundred and twenty-six articles of interest were found; of these, 65 articles that presented novel treatments of urological neoplasms, discussed precision medicine, genomic expression profiles and biomarkers in urology, and latest deep learning and machine learning algorithms as well as the use of artificial intelligence in urological practice were selected. A critical review of the literature is presented in the present article. Urology is a constantly changing specialty with a wide range of therapeutic breakthroughs, a huge understanding of the genomic expression profiles for each urological cancer and a tendency to use cutting-edge technology to treat our patients. All of these major developments must be analyzed objectively, taking into account costs to the health systems, risks and benefits to the patients, and the legal background that comes with them. A critical analysis of these new technologies and pharmacological breakthroughs should be made before considering changing our clinical practice. Nowadays, research needs to be strengthened to help us improve results in assessing and treating our patients

La medicina de precisión juega un rol fundamental en la práctica clínica de la urologia oncológica en la actualidad, con el desarrollo de los inhibidores de la poli (ADP-ribosa) polimerasa (PARPi), que juegan un papel fundamental en las distintas vías del reparo del ADN dañado (RAD), los inhibidores del punto de chequeo inmune (ICI), los perfiles de expresión genómicos, y la terapia blanco-dirigida a la manipulación genómica. El desarrollo tecnológico y la informática están cambiando la forma como evaluamos y tratamos a los pacientes, y se debe discutir y revisar a detalle. El objetivo de este artículo es hacer una revisión detallada acerca de la medicina de precisión, genómica, y los avances tecnológicos en nuestro campo. Realizamos una revisión de la literatura en cuatro bases de datos diferentes (PubMed, Embase, Lilacs, y Scielo), buscando cualquier información relacionada con cáncer de próstata, vejiga, riñón y carcinoma urotelial, tratamientos novedosos con PARPi, ICI, terapia-blanco con inhibidores del receptor del factor de crecimiento de los fibroblastos (FGFRi) y teragnósticos con anticuerpos monoclonales dirigidos al antígeno de membrana específico de la próstata (AMEP). Inteligencia artificial, aprendizaje de máquinas y algoritmos de aprendizaje profundo en la práctica urológica también fueron revisados. Incluimos artículos escritos en inglés, publicados dentro de los últimos 7 años, que abordaran terapias novedosas y genómica en cáncer urológico e inteligencia artificial aplicada a la urología. Excluimos artículos con falta de una metodología adecuada y escritos en cualquier idioma diferente al inglés. En total, 126 artículos de interés fueron encontrados, y, de estos seleccionamos 65 artículos que reportaban tratamientos novedosos para neoplasias urológicas, discutían medicina de precisión y perfiles de expresión genómica y bio-marcadores en urología, algoritmos de aprendizaje profundo, aprendizaje de máquina, y el uso de inteligencia artificial en la práctica urológica. Se hizo una revisión crítica de la literatura que se presenta en este artículo. La urología es una especialidad constantemente en cambio, con un gran rango de avances terapéuticos, un gran conocimiento de los perfiles de expresión genómica para cada cáncer urológico, y una tendencia a utilizar tecnología de punta para estudiar y tratar a nuestros pacientes. Todos estos desarrollos se deben analizar objetivamente, y hay que tener en cuenta los costos al sistema de salud, los riesgos y beneficios para los pacientes, y el contexto legal que implica cada uno. Hasta la fecha, estos avances tecnológicos y farmacológicos se deben analizar con cautela antes de vernos en la posición de cambiar nuestra práctica clínica. Se debe fortalecer la investigación médica para mejorar los resultados en el tratamiento y abordaje de nuestros pacientes.

Actively priming autophagic cell death with novel transferrin receptor-targeted nanomedicine for synergistic chemotherapy against breast cancer

Recently, considerable attention in the field of cancer therapy has been focused on the mammalian rapamycin target (mTOR), inhibition of which could result in autophagic cell death (ACD). Though novel combination chemotherapy of autophagy inducers with chemotherapeutic agents is extensively investigated, nanomedicine-based combination therapy for ACD remains in infancy. In attempt to actively trigger ACD for synergistic chemotherapy, here we incorporated autophagy inducer rapamycin (RAP) into 7pep-modified PEG-DSPE polymer micelles (7pep-M-RAP) to specifically target and efficiently priming ACD of MCF-7 human breast cancer cells with high expression of transferrin receptor (TfR). Cytotoxic paclitaxel (PTX)-loaded micelle (7pep-M-PTX) was regarded as chemotherapeutic drug model. We discovered that with superior intracellular uptake and more tumor accumulation of micelles , 7pep-M-RAP exhibited excellent autophagy induction and synergistic antitumor efficacy with 7pep-M-PTX. Mechanism study further revealed that 7pep-M-RAP and 7pep-M-PTX used in combination provided enhanced efficacy through induction of both apoptosis- and mitochondria-associated autophagic cell death. Together, our findings suggested that the targeted excess autophagy may provide a rational strategy to improve therapeutic outcome of breast cancer, and simultaneous induction of ACD and apoptosis may be a promising anticancer modality.