High-Grade Endometrial Cancer: Molecular Subtypes, Current Challenges, and Treatment Options.

Although many recent advancements have been made in women's health, perhaps one of the most neglected areas of research is the diagnosis and treatment of high-grade endometrial cancer (EnCa). The molecular classification of EnCa in concert with histology was a major step forward. The integration of profiling for mismatch repair deficiency and Human Epidermal Growth Factor 2 (HER2) overexpression, can further inform treatment options, especially for drug resistant recurrent disease.

Combination Organelle Mitochondrial Endoplasmic Reticulum Therapy (COMET) for Multidrug Resistant Breast Cancer.

It is time for the story of mitochondria and intracellular communication in multidrug resistant cancer to be rewritten. Herein we characterize the extent and cellular advantages of mitochondrial network fusion in multidrug resistant (MDR) breast cancer and have designed a novel nanomedicine that disrupts mitochondrial network fusion and systematically manipulates organelle fusion and function. Combination Organelle Mitochondrial Endoplasmic reticulum Therapy (COMET) is an innovative translational nanomedicine for treating MDR triple negative breast cancer (TNBC) that has superior safety and equivalent efficacy to the current standard of care (paclitaxel).

Lessons learned from the SARS-CoV-2 pandemic; from nucleic acid nanomedicines, to clinical trials, herd immunity, and the vaccination divide.

Introduction: In November 2019, the idea of a zoonotic virus crossing over to human transmission in a seafood market in Wuhan, China, and then soaring across the globe to claim over 6.3 million lives and persisting to date, seemed more like wild science fiction than a future reality. As the SARS-CoV-2 pandemic continues, it is important to hallmark the imprints the pandemic has made on science.

Mitochondrial nanomedicine: Subcellular organelle-specific delivery of molecular medicines.

As mitochondria network together to act as the master sensors and effectors of apoptosis, ATP production, reactive oxygen species management, mitophagy/autophagy, and homeostasis; this organelle is an ideal target for pharmaceutical manipulation. Mitochondrial dysfunction contributes to many diseases, for example, β-amyloid has been shown to interfere with mitochondrial protein import and induce apoptosis in Alzheimer's Disease while some forms of Parkinson's Disease are associated with dysfunctional mitochondrial PINK1 and Parkin proteins. Mitochondrial medicine has applications in the treatment of an array of pathologies from cancer to cardiovascular disease.

Clinical approval of nanotechnology-based SARS-CoV-2 mRNA vaccines: impact on translational nanomedicine.

One year after the first human case of SARS-CoV-2, two nanomedicine-based mRNA vaccines have been fast-tracked, developed, and have received emergency use authorization throughout the globe with more vaccine approvals on the heels of these first two. Several SARS-CoV-2 vaccine compositions use nanotechnology-enabled formulations. A silver lining of the COVID-19 pandemic is that the fast-tracked vaccine development for SARS-CoV-2 has advanced the clinical translation pathway for nanomedicine drug delivery systems.

Technologies and Standardization in Research on Extracellular Vesicles.

Extracellular vesicles (EVs) are phospholipid bilayer membrane-enclosed structures containing RNAs, proteins, lipids, metabolites, and other molecules, secreted by various cells into physiological fluids. EV-mediated transfer of biomolecules is a critical component of a variety of physiological and pathological processes. Potential applications of EVs in novel diagnostic and therapeutic strategies have brought increasing attention.

Genetic and epigenetic strategies for advancing ovarian cancer immunotherapy.

Introduction: Immuno-oncology is currently the most popular field of cancer research and development. The surge of interest in immuno-oncology stems from recent clinical approvals and successes in clinical trials with new immuno-therapeutics and parallels a global trending interest in immunology. Among the current immunotherapeutic modalities, immune checkpoint inhibitors (ICPIs) are some of the most prominent agents that strengthens the activity of our adaptive immune system, and has demonstrated success in treating different types of cancer.

Hyaluronic acid targeting of CD44 for cancer therapy: from receptor biology to nanomedicine.

Cluster of differentiation-44 (CD44) is a ubiquitously present glycoprotein on the surface of mammalian cells that plays a significant role in a number of biological functions. Since the discovery that the receptor is over-expressed in a variety of solid tumors, such as pancreatic, breast and lung cancer, many studies have focused on methods for targeting CD44 in an attempt to improve drug delivery and discrimination between healthy and malignant tissue, while reducing residual toxicity and off-target accumulation. In this review, we describe CD44 receptor biology and its involvement in the different stages of tumor growth and metastasis, as well as methods currently used for targeting the receptor.

Exosome mediated communication within the tumor microenvironment.

It is clear that exosomes (endosome derived vesicles) serve important roles in cellular communication both locally and distally and that the exosomal process is abnormal in cancer. Cancer cells are not malicious cells; they are cells that represent 'survival of the fittest' at its finest. All of the mutations, abnormalities, and phenomenal adaptations to a hostile microenvironment, such as hypoxia and nutrient depletion, represent the astute ability of cancer cells to adapt to their environment and to intracellular changes to achieve a single goal - survival.

Mitochondrial biology, targets, and drug delivery.

In recent years, mitochondrial medicine has emerged as a new discipline resting at the intersection of mitochondrial biology, pathology, and pharmaceutics. The central role of mitochondria in critical cellular processes such as metabolism and apoptosis has placed mitochondria at the forefront of cell science. Advances in mitochondrial biology have revealed that these organelles continually undergo fusion and fission while functioning independently and in complex cellular networks, establishing direct membrane contacts with each other and with other organelles.

Targeted cancer therapy; nanotechnology approaches for overcoming drug resistance.

Recent advances in cancer molecular biology have resulted in parallel and unprecedented progress in the development of targeted cancer therapy. Targeted therapy can provide higher efficacy and lower toxicity than conventional chemotherapy for cancer. However, like traditional chemotherapy, molecularly targeted cancer therapy also faces the challenge of drug resistance.

Cluster of Differentiation 44 Targeted Hyaluronic Acid Based Nanoparticles for MDR1 siRNA Delivery to Overcome Drug Resistance in Ovarian Cancer.

Purpose: Approaches for the synthesis of biomaterials to facilitate the delivery of "biologics" is a major area of research in cancer therapy. Here we designed and characterized a hyaluronic acid (HA) based self-assembling nanoparticles that can target CD44 receptors overexpressed on multidrug resistance (MDR) ovarian cancer. The nanoparticle system is composed of HA-poly(ethyleneimine)/HA-poly(ethylene glycol) (HA-PEI/HA-PEG) designed to deliver MDR1 siRNA for the treatment of MDR in an ovarian cancer model.

Therapeutic efficacy and safety of paclitaxel/lonidamine loaded EGFR-targeted nanoparticles for the treatment of multi-drug resistant cancer.

The treatment of multi-drug resistant (MDR) cancer is a clinical challenge. Many MDR cells over-express epidermal growth factor receptor (EGFR). We exploit this expression through the development of EGFR-targeted, polymer blend nanocarriers for the treatment of MDR cancer using paclitaxel (a common chemotherapeutic agent) and lonidamine (an experimental drug; mitochondrial hexokinase 2 inhibitor).

Multi-modal strategies for overcoming tumor drug resistance: hypoxia, the Warburg effect, stem cells, and multifunctional nanotechnology.

Inefficiencies in systemic drug delivery and tumor residence as well as micro-environmental selection pressures contribute to the development of multidrug resistance (MDR) in cancer. Characteristics of MDR include abnormal vasculature, regions of hypoxia, up-regulation of ABC-transporters, aerobic glycolysis, and an elevated apoptotic threshold. Nano-sized delivery vehicles are ideal for treating MDR cancer as they can improve the therapeutic index of drugs and they can be engineered to achieve multifunctional parameters.

Role of hypoxia and glycolysis in the development of multi-drug resistance in human tumor cells and the establishment of an orthotopic multi-drug resistant tumor model in nude mice using hypoxic pre-conditioning.

Background: The development of multi-drug resistant (MDR) cancer is a significant challenge in the clinical treatment of recurrent disease. Hypoxia is an environmental selection pressure that contributes to the development of MDR. Many cancer cells, including MDR cells, resort to glycolysis for energy acquisition.

Pharmacokinetics and biodistribution of lonidamine/paclitaxel loaded, EGFR-targeted nanoparticles in an orthotopic animal model of multi-drug resistant breast cancer.

Unlabelled: The aim of this study was to assess the biodistribution and pharmacokinetics of epidermal growth factor receptor (EGFR)-targeted polymer-blend nanoparticles loaded with the anticancer drugs lonidamine and paclitaxel. Plasma, tumor, and tissue distribution profiles were quantified in an orthotopic animal model of multidrug-resistant breast cancer and were compared to treatment with nontargeted nanoparticles and to treatment with drug solution. A poly(d,l-lactide-co-glycolide)-poly(ethylene glycol)-EGFR targeting peptide (PLGA-PEG-EFGR peptide) construct was synthesized for incorporation in poly(ɛ-caprolactone) particles to achieve active EGFR targeting.

Development of EGFR-targeted polymer blend nanocarriers for combination paclitaxel/lonidamine delivery to treat multi-drug resistance in human breast and ovarian tumor cells.

Multi-drug resistant (MDR) cancer is a significant clinical obstacle and is often implicated in cases of recurrent, nonresponsive disease. Targeted nanoparticles were made by synthesizing a poly(D,L-lactide-co-glycolide)/poly(ethylene glycol)/epidermal growth factor receptor targeting peptide (PLGA/PEG/EGFR-peptide) construct for incorporation in poly(epsilon-caprolactone) (PCL) nanoparticles. MDR was induced in a panel of nine human breast and ovarian cancer cell lines using hypoxia.

Inhibition of ABCB1 (MDR1) expression by an siRNA nanoparticulate delivery system to overcome drug resistance in osteosarcoma.

Background: The use of neo-adjuvant chemotherapy in treating osteosarcoma has improved patients' average 5 year survival rate from 20% to 70% in the past 30 years. However, for patients who progress after chemotherapy, its effectiveness diminishes due to the emergence of multi-drug resistance (MDR) after prolonged therapy.

Methodology/principal Findings: In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure resulting from MDR, we designed and evaluated a novel drug delivery system for MDR1 siRNA delivery.

Nanoparticles: a promising modality in the treatment of sarcomas.

Improvements in surgical technique, chemotherapy, and radiotherapy have enhanced the prognosis of sarcoma patients, but have since reached a plateau in recent years. Novel approaches have been sought but with limited results. Nanomedicine offers solutions in diverse areas of sarcoma therapy including diagnosis and treatment.

Label-free Raman spectral imaging of intracellular delivery and degradation of polymeric nanoparticle systems.

Novel optical imaging methods, such as Raman microspectroscopy, have been gaining recognition in their ability to obtain noninvasively the distribution of biochemical components of a sample. Raman spectroscopy in combination with optical microscopy provides a label-free method to assess and image cellular processes, without the use of extrinsic fluorescent dyes. The submicrometer resolution of the confocal Raman instrumentation allows us to image cellular organelles on the scale of conventional microscopy.