Background: Extracellular vesicles (EVs) are cell-secreted particles conceived as natural vehicles for intercellular communication. The capacity to entrap heterogeneous molecular cargoes and target specific cell populations through EV functionalization promises advancements in biomedical applications. However, the efficiency of the obtained EVs, the contribution of cell-exposed receptors to EV interactions, and the predictability of functional cargo release with potential sharing of high molecular weight recombinant mRNAs are crucial for advancing heterologous EVs in targeted therapy applications.
View Article and Find Full Text PDFImmunotherapy has become an important part of the oncotherapy arsenal. Its applicability in various cancer types is impressive, as well as its use of endogenous mechanisms to achieve desired ends. However, off-target or on-target-off-tumor toxicity, limited activity, lack of control in combination treatments and, especially for solid tumors, low local accumulation, have collectively limited clinical use thereof.
View Article and Find Full Text PDFCervical cancer is the fourth most common cancer in women worldwide and is caused by persistent infection with high-risk types of human papillomavirus (HPV). HPV viral load, the amount of HPV DNA in a sample, has been suggested to correlate with cervical disease severity, and with clinical outcome of cervical cancer. In this systematic review, we searched three databases (EMBASE, PubMed, Web of Science) to examine the current evidence on the association between HPV viral load in cervical samples and disease severity, as well as clinical outcome.
View Article and Find Full Text PDFTheranostics
January 2024
[This corrects the article DOI: 10.7150/thno.37949.
View Article and Find Full Text PDFInt J Radiat Oncol Biol Phys
March 2024
Purpose: Hyperthermia is a potent sensitizer of radiation therapy that improves both tumor control and survival in women with locally advanced cervical cancer (LACC). The optimal sequence and interval between hyperthermia and radiation therapy are still under debate.
Methods And Materials: We investigated the interval and sequence in vitro in cervical cancer cell lines, patient-derived organoids, and SiHa cervical cancer hind leg xenografts in athymic nude mice and compared the results with retrospective results from 58 women with LACC treated with thermoradiotherapy.
It is well known that metal-organic framework (MOF) nanostructures have unique characteristics such as high porosity, large surface areas and adjustable functionalities, so they are ideal candidates for developing drug delivery systems (DDSs) as well as theranostic platforms in cancer treatment. Despite the large number of MOF nanostructures that have been discovered, conventional MOF-derived nanosystems only have a single biofunctional MOF source with poor colloidal stability. Accordingly, developing core-shell MOF nanostructures with good colloidal stability is a useful method for generating efficient drug delivery, multimodal imaging and synergistic therapeutic systems.
View Article and Find Full Text PDFIt is essential to develop ultrasensitive biosensors for cancer detection and treatment monitoring. In the development of sensing platforms, metal-organic frameworks (MOFs) have received considerable attention as potential porous crystalline nanostructures. Core-shell MOF nanoparticles (NPs) have shown different diversities, complexities, and biological functionalities, as well as significant electrochemical (EC) properties and potential bio-affinity to aptamers.
View Article and Find Full Text PDFHigh mobility group A 2 (HMGA2) is a protein that modulates the structure of chromatin in the nucleus. Importantly, aberrant expression of HMGA2 occurs during carcinogenesis, and this protein is an upstream mediator of cancer hallmarks including evasion of apoptosis, proliferation, invasion, metastasis, and therapy resistance. HMGA2 targets critical signaling pathways such as Wnt/β-catenin and mTOR in cancer cells.
View Article and Find Full Text PDFCell migration is a very dynamic process involving several chemical as well as biological interactions with other cells and the environment. Several models exist to study cell migration ranging from simple 2D in vitro cultures to more demanding 3D multicellular assays, to complex evaluation in animals. High-resolution 4D (XYZ, spatial + T, time dimension) intravital imaging using transgenic animals with a fluorescent label in cells of interest is a powerful tool to study cell migration in the correct environment.
View Article and Find Full Text PDFObjective: Breast cancer accounts for significant mortality worldwide. Here, we develop a localized, sustained-release delivery system for breast cancer therapy.
Methods: Sirolimus (SIR) core-shell nanofibers (NFs) are fabricated by coaxial electrospinning with poly(ε-caprolactone) (PCL) for the core and chitosan and PCL for the shell.
The past decades have shown significant advancements in the development of solid tumor treatment. For instance, implementation of nanosystems for drug delivery has led to a reduction in side effects and improved delivery to the tumor region. However, clinical translation has faced challenges, as tumor drug levels are still considered to be inadequate.
View Article and Find Full Text PDFInt J Biol Macromol
January 2023
It has long been known that inorganic nanoparticles (NPs) can interact with biological macromolecules and show a wider range of biomedical characteristics, including antibacterial, anticancer and antioxidant effects, which cannot be mimicked by their bulky counterparts. It is of great importance in their biomedical applications to study DNA damage in bacterial and cancer cells to develop biocompatible therapeutic nano-platforms derived from inorganic NPs. Therefore, to determine how DNA interacts with inorganic NPs serving as therapeutic agents, thermodynamic and structural studies are essential for an understanding of those mechanisms, thereby allowing for their modulation and manipulation of nano-bio interface.
View Article and Find Full Text PDFAt the Nanomedicine Innovation Center (NICE) at the Erasmus MC in Rotterdam, we have approached the treatment of cancer by starting with a vision of first establishing a platform that enables us to overcome the low levels of drugs delivered to tumors and the issue of dose-limiting toxicity. Showing that a reduction of the volume of distribution, and a lowering of toxicity and side-effects, accompanied by augmented intratumoral drug delivery, could change outcomes in patients, paved the way to target, not only localized disease, but also systemic and metastasized cancers. In particular, the detailed studies with intravital microscopy we performed at NICE provided us with the necessary insights and affected to a large extent our program on liposome-based cancer therapy.
View Article and Find Full Text PDFNanoparticles (Nps) have revolutionized the landscape of many treatments, by modifying not only pharmacokinetic properties of the encapsulated agent, but also providing a significant protection of the drug from non-desired interactions, and reducing side-effects of the enclosed therapeutic, enabling co-encapsulation of possibly synergistic compounds or activities, allowing a controlled release of content and improving the therapeutic effect. Nevertheless, in systemic circulation, Nps suffer a rapid removal by opsonisation and the action of Mononuclear phagocyte system (MPS). To overcome this problem, different polymers, in particular Polyethyleneglycol (PEG), have been used to cover the surface of these nanocarriers forming a hydrophilic layer that allows the delay of the removal.
View Article and Find Full Text PDFHeat-triggered drug release from temperature-sensitive nanocarriers upon the application of mild hyperthermia is a promising approach to achieve site-specific delivery of drugs. The combination of mild hyperthermia (41-42 °C) and temperature-sensitive liposomes (TSL) that undergo lipid phase-transition and drug release has been studied extensively and has shown promising therapeutic outcome in a variety of animal tumor models as well as initial indications of success in humans. Sensitization of liposomes to mild hyperthermia by means of exploiting the thermal behavior of temperature-sensitive polymers (TSP) provides novel opportunities.
View Article and Find Full Text PDFAs bone grafts become more commonly needed by patients and as donors become scarcer, acellularized bone grafts (ABGs) are becoming more popular for restorative purposes. While autogeneic grafts are reliable as a gold standard, allogeneic and xenogeneic ABGs have been shown to be of particular interest due to the limited availability of autogeneic resources and reduced patient well-being in long-term surgeries. Because of the complete similarity of their structures with native bone, excellent mechanical properties, high biocompatibility, and similarities of biological behaviors (osteoinductive and osteoconductive) with local bones, successful outcomes of allogeneic and xenogeneic ABGs in both and research have raised hopes of repairing patients' bone injuries in clinical applications.
View Article and Find Full Text PDFTumorectomy followed by radiotherapy, hormone, and chemotherapy, are the current mainstays for breast cancer treatment. However, these strategies have systemic toxicities and limited treatment outcomes. Hence, there is a crucial need for a novel controlled release delivery system for implantation following tumor resection to effectively prevent recurrence.
View Article and Find Full Text PDFThe enhanced permeability and retention (EPR) effect in cancer treatment is one of the key mechanisms that enables drug accumulation at the tumor site. However, despite a plethora of virus/inorganic/organic-based nanocarriers designed to rely on the EPR effect to effectively target tumors, most have failed in the clinic. It seems that the non-compliance of research activities with clinical trials, goals unrelated to the EPR effect, and lack of awareness of the impact of solid tumor structure and interactions on the performance of drug nanocarriers have intensified this dissatisfaction.
View Article and Find Full Text PDFNanoparticles (NPs) have been used in numerous applications as anticancer, antibacterial and antioxidant agents. Artificial engineering of protein interactions with NPs in biological systems is crucial to develop potential NPs for drug delivery and cancer nanotherapy. The protein corona (PC) on the NP surface, displays an interface between biomacromolecules and NPs, governing their pharmacokinetics and pharmacodynamics.
View Article and Find Full Text PDFTargeting microtubules (MTs), dynamic and stable proteins in cells, by different ligands have been reported to be a potential strategy to combat cancer cells. Inorganic nanoparticles (NPs) have been widely used as anticancer, antibacterial and free radical scavenging agents, where they come in contact with biological macromolecules. The interaction between the NPs and biological macromolecules like MTs frequently occurs through different mechanisms.
View Article and Find Full Text PDFMethods that allow real-time, longitudinal, intravital detection of the fluorescence distribution and the cellular and vascular responses within tumor and normal tissue are important tools to obtain valuable information when investigating new photosensitizers and photodynamic therapy (PDT) responses. Intravital confocal microscopy using the dorsal skinfold chamber model gives the opportunity to visualize and determine the distribution of photosensitizers within tumor and normal tissue. Next to that, it also allows the visualization of the effect of treatment with respect to changes in vascular diameter and blood flow, vascular leakage, and tissue necrosis, in the first days post-illumination.
View Article and Find Full Text PDFNowadays, nano-/micro-motors are considered as powerful tools in different areas ranging from cleaning all types of contaminants, to development of Targeted drug delivery systems and diagnostic activities. Therefore, the development and application of nano-/micro-motors based on metal-organic frameworks with nanozyme activity (abbreviated as: MOF-NZs) in biomedical activities have received much interest recently. Therefore, after investigating the catalytic properties and applications of MOF-NZs in the treatment of cancer, this study intends to point out their key role in the production of biocompatible nano-/micro-motors.
View Article and Find Full Text PDFModification with polyethylene glycol (PEGylation) and the use of rigid phospholipids drastically improve the pharmacokinetics of chemotherapeutics and result in more manageable or reduced side-effects. A major drawback is retarded cellular delivery of content, which, along with tumor heterogeneity, are the two main obstacles against tumor targeting. To enhance cellular delivery and reach a bigger area of a tumor, we designed liposomes decorated with two ligands: one for targeting tumor vasculature via a cyclic-pentapeptide containing arginine-glycine-aspartic acid (RGD), which impacts tumor independent of passive accumulation inside tumors, and one for extravascular targeting of tumor cells via a cell-penetrating peptide derived from human immunodeficiency virus type 1 transactivator of transcription (TAT).
View Article and Find Full Text PDFCancer immunotherapy, a promising and widely applied mode of oncotherapy, makes use of immune stimulants and modulators to overcome the immune dysregulation present in cancer, and leverage the host's immune capacity to eliminate tumors. Although some success has been seen in this field, toxicity and weak immune induction remain challenges. Liposomal nanosystems, previously used as targeting agents, are increasingly functioning as immunotherapeutic vehicles, with potential for delivery of contents, immune induction, and synergistic drug packaging.
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