Protease-triggered bioresponsive drug delivery for the targeted theranostics of malignancy

Proteases have a fundamental role in maintaining physiological homeostasis, but their dysregulation results in severe activity imbalance and pathological conditions, including cancer onset, progression, invasion, and metastasis. This striking importance plus superior biological recognition and catalytic performance of proteases, combining with the excellent physicochemical characteristics of nanomaterials, results in enzyme-activated nano-drug delivery systems (nanoDDS) that perform theranostic functions in highly specific response to the tumor phenotype stimulus. In the tutorial review, the key advances of protease-responsive nanoDDS in the specific diagnosis and targeted treatment for malignancies are emphatically classified according to the effector biomolecule types, on the premise of summarizing the structure and function of each protease. Subsequently, the incomplete matching and recognition between enzyme and substrate, structural design complexity, volume production, and toxicological issues related to the nanocomposites are highlighted to clarify the direction of efforts in nanotheranostics. This will facilitate the promotion of nanotechnology in the management of malignant tumors.

Progress in nanodrug delivery system combined with photothermal therapy to treat multidrug resistance of tumor / 肿瘤

Multidrug resistance is one of the main causes of chemotherapy failure. In the past few decades, the development of nanotechnology has brought great hopes for the treatment of malignant tumors. Nanodrug delivery system effectively delivers the drug by endocytosis to avoid the drug being pumped out of the P-glycoprotein efflux pump, increasing the accumulation of the drug at the tumor site and reducing the toxicity of chemotherapeutic agents. Photothermal therapy uses the near-infrared laser for thermal ablation of tumors. The conversion of near-infrared light into high heat kills tumors, which is a new strategy for treating tumors. The use of nano-drug delivery system and photothermal therapy to overcome the multidrug resistance of tumors has incomparable advantages over traditional treatment. This paper reviewed the mechanism of multidrug resistance, the principle of reversal, the application of nano-drug delivery system and photothermal therapy in the reversal of multidrug resistance, the existing problems and prospects, in order to provide a new idea for reversing drug resistance.

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.

Progress of antitumor mechanisms of humic acids / 肿瘤研究与临床

Humic acids, a complex macromolecular organic carbon resources, contain different functional groups such as quinones, phenols, carboxylic acids, hydroxyl, and aromatic structures. The various functions and pharmacological activities are mainly attributable to the different functional groups of humic acids. In recent years, studies show that antitumor effect of humic acids can be analyzed from activation of immune system, induction of cell injury and apoptosis, photothermal reaction, or binding with other materials. This paper reviews the progress of antitumor mechanisms of humic acids.

Surface-enhanced Raman nanoparticles for cancer theranostics / 中华核医学与分子影像杂志

Raman spectroscopy is amplified by surface-enhanced Raman scattering nanoparticles(SERS-NPs),and Raman signal can be enhanced by SERS-NPs,which can achieve high-resolution imaging of tumors.Meanwhile,SERS-NPs have high molecular specificity and sensitivity,showing a good prospect of tumor diagnosis and treatment.The advantages of SERS-NPs and its application in tumor diagnosis and treatment,and related experimental studies are reviewed in this article.

Application of iron oxide magnetic nanoparticles in tumor theranostics / 中国药科大学学报

@#With the rapid development of nanotechnology, accurate personalized treatments for tumor have attracted more attention to increase the therapeutic effects and reduce the side effects. The emerging theranostic systems incorporating different therapeutic and diagnostic imaging capabilities have become a new research hotspot. Magnetic iron oxide nanoparticles(IONP)have been widely used in theranostic systems due to their unique imaging properties, stable thermal performance, excellent biocompatibility and admirable surface modifiability. In this review, we analyzed the advantages of IONP in the diagnosis and the treatment of tumor, and detailedly introduced the relevant strategies and latest research progress, including magnetic resonance imaging(MRI), photothermal therapy, magnetic hyperthermia, and magnetic targeted drug delivery, etc. Finally, the potential application of IONP in the clinical tumor theranostics was proposed.

Theranostic nanoparticles with tumor-specific enzyme-triggered size reduction and drug release to perform photothermal therapy for breast cancer treatment

Although progress has been indeed made by nanomedicines, their efficacies for cancer treatment remain low, consequently leading to failures in translation to clinic. To improve the drug delivery efficiency, nanoparticles need to change size so as to fully utilize the enhanced permeability and retention (EPR) effect of solid tumor, which is the golden principle of nanoparticles used for cancer treatment. Herein, we employed cationic small-sized red emission bovine serum albumin (BSA) protected gold nanocluster (AuNC@CBSA, 21.06 nm) to both load indocyanine green (ICG) and act as imaging probe to realize theranostic. Then AuNC@CBSA-ICG was fabricated with negatively charged hyaluronic acid (HA) to form AuNC@CBSA-ICG@HA, which was about 200 nm to easily retain at tumor site and could be degraded by tumor-specific hyaluronidase into small nanoparticles for deep tumor penetration. The HA shell also endowed AuNC@CBSA-ICG@HA with actively targeting ability and hyaluronidase-dependent drug release. Furthermore, the quenching and recovery of fluorescence revealed the interaction between ICG and carrier, which was essential for the investigation of pharmacokinetic profiles. No matter or , AuNC@CBSA-ICG@HA showed markedly anti-tumor effect, and could suppress 95.0% of tumor growth on mice breast cancer model. All results demonstrated AuNC@CBSA-ICG@HA was potential for breast cancer therapy.

Current Status and Growth of Nuclear Theranostics in Singapore / 대한핵의학회잡지

The concept of theranostics, where individual patient-level biological information is used to choose the optimal therapy for that individual, has become more popular in the modern era of ‘personalised’ medicine. With the growth of theranostics, nuclear medicine as a specialty is uniquely poised to grow along with the ever-increasing number of concepts combining imaging and therapy. This special report summarises the status and growth of Theranostic Nuclear Medicine in Singapore.We will cover our experience with the use of radioiodine, radioiodinated metaiodobenzylguanidine, peptide receptor radionuclide therapy, prostate specific membrane antigen radioligand therapy, radium-223 and yttrium-90 selective internal radiation therapy.We also include a section on our radiopharmacy laboratory, crucial to our implementation of theranostic principles. Radionuclide theranostics has seen tremendous growth and we hope to be able to grow alongside to continue to serve the patients in Singapore and in the region.

Research situation of pH low insertion peptides / 药学学报

Extracellular acidity has been associated with many pathological states, such as cancer, ischemic stroke, neurotrauma and infection, which makes it an effective target for therapy and diagnosis of such diseases. As a polypeptide vector, pH low insertion peptides (pHLIPs) are endowed with high sensitivity to extracellular acidic environment, which can insert the membrane and deliver payload to pathological cells in a pH dependent manner. Here, theranostic applications of pHLIP in disease, are reviewed in two aspects:pHLIP-mediated single-molecule transporter and nano-sized carrier.

Small conjugate-based theranostic agents:a tumour microenvironment responsive approach for cancer therapy / 中国药科大学学报

@#Theranostics, combining therapy and diagnosis, is an appealing approach for chemotherapy in medicine which exhibits improved biodistribution, selective cancer targeting ability, reduced toxicity, masked drug efficacy, and minimum side effects. The role of diagnosis tools in theranostics is to collect the information of the disease state before and after specific treatment. Currently, small conjugate-based systems have received much attention for cancer treatment and diagnosis. Relative to the normal tissues, tumor microenvironment shows great difference, including acidic excessive expression of various enzymes as well as low oxygen. In this review, the latest developments on small conjugate based theranostic agents for tumor treatment and diagnosis using fluorescence were summarized.

Nanoimaging in cardiovascular diseases: Current state of the art.

Nanotechnology has been integrated into healthcare system in terms of diagnosis as well as therapy. The massive impact of imaging nanotechnology has a deeper intervention in cardiology i.e. as contrast agents , to target vulnerable plaques with site specificity and in a theranostic approach to treat these plaques, stem cell delivery in necrotic myocardium, etc. Thus cardiovascular nanoimaging is not limited to simple diagnosis but also can help real time tracking during therapy as well as surgery. The present review provides a comprehensive description of the molecular imaging techniques for cardiovascular diseases with the help of nanotechnology and the potential clinical implications of nanotechnology for future applications.

Unique roles of nanotechnology in medicine and cancer‑II.

Applications of nanotechnology in medicine and cancer are becoming increasingly popular. Common nanomaterials and devices applicable in cancer medicine are classifiable as liposomes, polymeric‑micelles, dendrimers, nano‑cantilevers, carbon nanotubes, quantum dots, magnetic‑nanoparticles, gold nanoparticles (AuNPs) and certain miscellaneous nanoparticles. Here, we present review of the structure, function and utilities of the various approved, under trial and pretrial nanodevices applicable in the cancer care and medicine. The liposomes are phospholipid‑vesicles made use in carrying drugs to the target site minimizing the bio‑distribution toxicity and a number of such theranostics have been approved for clinical practice. Newly worked out liposomes and polymeric micelles are under the trail phases for nano‑therapeutic utility. A multifunctional dendrimer conjugate with imaging, targeting and drug molecules of paclitaxel has been recently synthesized for cancer theranostic applications. Nano‑cantilever based assays are likely going to replace the conventions methods of chemical pathological investigations. Carbon nanotubes are emerging for utility in regenerative and cancer medicine. Quantum dots hold great promise for the micro‑metastasis and intra‑operative tumor imaging. Important applications of magnetic nanoparticles are in the cardiac stents, photodynamic therapy and liver metastasis imaging. The AuNPs have been employed for cell imaging, computed tomography and cancer therapy. Besides these categories, miscellaneous other nanoparticles are being discovered for utility in the cancer diagnosis and disease management. However, the use of nanoparticles should be cautious since the toxic effects of nanoparticles are not well‑known. The use of nanoparticles in the clinical practice and their toxicity profile require further extensive research.