Three‐dimensional cell culture models, such as spheroids, can be used in the process of the development of new anticancer agents because they are able to closely mimic the main features of human ...solid tumors, namely their structural organization, cellular layered assembling, hypoxia, and nutrient gradients. These properties imprint to the spheroids an anticancer therapeutics resistance profile, which is similar to that displayed by human solid tumors. In this review, an overview of the drug resistance mechanisms observed in 3D tumor spheroids is provided. Furthermore, comparisons between the therapeutics resistance profile exhibited by spheroids, and 2D cell cultures are presented. Finally, examples of the therapeutic approaches that have been developed to surpass the drug resistance mechanisms exhibited by spheroids are described.
Drug resistance phenotype acquired by the cancer cells is still the major cause of the patient’s low survival rates. Spheroids in vitro models represent more closely the characteristics of the human tumors, which prompted its use in the development of new therapeutics. In this review, the structural and functional similarities between spheroids and in vivo human solid tumors are reviewed, highlighting the common drug resistance mechanisms, as well as the therapeutic approaches explored to surpass this resistance.
HIGHLIGHTS
The suitability of 3D cell culture models for drug screening purposes is highlighted.
Spheroids and in vivo human solid tumors structural and functional similarities are emphasized.
The drug resistance mechanisms exhibited by spheroids are described.
Therapeutic approaches used to surpass spheroids’ drug resistance mechanisms are described.
Cancer photothermal therapy (PTT) has captured the attention of researchers worldwide due to its localized and trigger-activated therapeutic effect. In this field, nanomaterials capable of converting ...the energy of the irradiation light into heat have been showing promising results in several pre-clinical and clinical assays. Such a therapeutic modality takes advantage of the innate capacity of nanomaterials to accumulate in the tumor tissue and their capacity to interact with NIR laser irradiation to exert a therapeutic effect. Therefore, several nanostructures composed of different materials and organizations for mediating a photothermal effect have been developed. In this review, the most common inorganic nanomaterials, such as gold, carbon-based materials, tungsten, copper, molybdenum, and iron oxide, which have been explored for mediating a tumor-localized photothermal effect, are summarized. Moreover, the physicochemical parameters of nanoparticles that influence the PTT effectiveness are discussed and the recent clinical advances involving inorganic nanomaterial-mediated cancer photothermal therapy are also presented.
Cancer photothermal therapy (PTT) has captured the attention of researchers worldwide due to its localized and trigger-activated therapeutic effect.
The wound healing process involves highly complex and dynamic events that allow the re-establishment of skin's structural integrity. To further improve or to overcome the drawbacks associated with ...this process, researchers have been focused on the development of new therapeutics. Among them, asymmetric membranes are currently one of the most promising approaches to be used in wound healing due to its structural similarities with the epidermal and dermal layers of the native skin. The outer layer of asymmetric membranes provides a barrier that protects the wound from external damages (e.g. microorganisms and chemical agents), whereas the interior porous layer acts as template for supporting cell adhesion, migration and proliferation. Among the different materials used to produce these distinct layers, the chitosan arises as one of the preeminent materials due to its inherent biocompatibility, antibacterial, hemostatic, and healing properties. Therefore, in this review, it is provided an overview of the different chitosan-based asymmetric membranes developed for wound dressing applications. Further, the chitosan modifications to enhance its bioactivity as well as the asymmetric membranes general properties and production techniques are also described.
Display omitted
•The asymmetric membranes' properties make them good candidates to be used as wound dressings.•The different techniques used to produce asymmetric membranes are described.•Different approaches followed to improve chitosan bioactivity are highlighted.•Chitosan-based asymmetric membranes application in wound healing is overviewed.
Spheroids have emerged as in vitro models that reproduce in a great extent the architectural microenvironment found in human tissues. However, the imaging of 3D cell cultures is highly challenging ...due to its high thickness, which results in a light‐scattering phenomenon that limits light penetration. Therefore, several optical clearing methods, widely used in the imaging of animal tissues, have been recently explored to render spheroids with enhanced transparency. These methods are aimed to homogenize the microtissue refractive index (RI) and can be grouped into four different categories, namely (a) simple immersion in an aqueous solution with high RI; (b) delipidation and dehydration followed by RI matching; (c) delipidation and hyperhydration followed by RI matching; and (d) hydrogel embedding followed by delipidation and RI matching. In this review, the main optical clearing methods, their mechanism of action, advantages, and disadvantages are described. Furthermore, the practical examples of the optical clearing methods application for the imaging of 3D spheroids are highlighted.
Spheroids have emerged as in vitro models that reproduce to a great extent the architectural microenvironment found in human tissues. However, the imaging of 3D cell cultures is highly challenging due to its high thickness, which results in a light‐scattering phenomenon that limits light penetration.
The plasmonic photothermal properties of gold nanoparticles have been widely explored in the biomedical field to mediate a photothermal effect in response to the irradiation with an external light ...source. Particularly, in cancer therapy, the physicochemical properties of gold-based nanomaterials allow them to efficiently accumulate in the tumor tissue and then mediate the light-triggered thermal destruction of cancer cells with high spatial-temporal control. Nevertheless, the gold nanomaterials can be produced with different shapes, sizes, and organizations such as nanospheres, nanorods, nanocages, nanoshells, and nanoclusters. These gold nanostructures will present different plasmonic photothermal properties that can impact cancer thermal ablation. This review analyses the application of gold-based nanomaterials in cancer photothermal therapy, emphasizing the main parameters that affect its light-to-heat conversion efficiency and consequently the photothermal potential. The different shapes/organizations (clusters, shells, rods, stars, cages) of gold nanomaterials and the parameters that can be fine-tuned to improve the photothermal capacity are presented. Moreover, the gold nanostructures combination with other materials (e.g. silica, graphene, and iron oxide) or small molecules (e.g. indocyanine green and IR780) to improve the nanomaterials photothermal capacity is also overviewed.
Display omitted
Nanomaterials have assumed a prominent role in biomedical field during the past years. Particularly, the gold-core silica shell nanoparticles present unique physical and chemical properties that make ...nanodevices appealing for theragnostic applications. The gold core characteristic X-ray attenuation, surface enhanced raman scattering and tunable absorption in the near-infrared region supports the applicability of these systems in X-ray, photoacoustic and thermal imaging as well as in photothermal and photodynamic based therapies. Additionally, the inclusion of the silica shell stabilizes the gold core, protecting it from premature degradation and aggregation, and also provides additional cargo capacity for therapeutic molecules. Further, both silica and gold are described as biocompatible, inert and nontoxic materials. In this review, an overview of the gold core-silica shell nanoparticles applications in nanomedicine is provided, highlighting the different particle shapes and their application in bioimaging and therapy. Further, the basics of the gold core-silica shell nanoparticles synthesis procedures, general properties, and biosafety are also described.
Display omitted
•Overview of gold-core silica shell nanoparticles (AuMSS) application in nanomedicine.•Different AuMSS core shapes and their properties are discussed.•Examples of AuMSS applied to imaging and therapeutic purposes are presented.
The application of nanocarriers as selective drug delivery platforms, as imaging or as diagnostic agents has been evaluated in several studies in the area of biomedicine, namely for cancer therapy. ...Such systems have the potential to perform a controlled and site-specific delivery of therapeutic agents leading to a reduction of side effects and, ultimately, to an improved therapeutic outcome. Among the different nanocarriers developed so far, mesoporous silica nanoparticles have attracted the attention of the scientific community for being applied as drug delivery systems that are capable of controlling, both in space and time, the drug release. In this review, the modifications performed, so far, on mesoporous silica nanoparticles to imprint them a stimulus responsive behavior (namely, pH, redox potential, adenosine triphosphate, enzyme or temperature) in order to allow their application in cancer therapy are highlighted.
Display omitted
•Overview of mesoporous silica nanoparticles (MSNs) as drug delivery systems.•MSNs surface modifications to confer a stimuli-responsive behavior are emphasized.•Examples of stimuli responsive MSNs applied to cancer drug delivery are presented.
Nowadays, wound dressings with improved properties are under development and among them, asymmetric membranes have gained an increasing interest due to their two-layered structure that mimic both the ...epidermis and dermis layers of the skin. Herein, a new asymmetric membrane was produced using the electrospinning technique. The top layer was produced with silk fibroin (SF) and poly(caprolactone) to reproduce the dense nature and waterproof ability of the epidermis. On the other hand, the dermis-like bottom layer was manufactured with SF and hyaluronic acid loaded with an herbal drug (thymol (THY)). All the data gathered showed that the produced electrospun asymmetric membrane exhibited the porosity, wettability, and mechanical properties suitable for the healing process. Further, the in vitro data also demonstrated that the human fibroblast is able to adhere and spread at the membranes' surface, thus confirming their biocompatibility. Moreover, the incorporation of THY into the bottom layer of the membrane, improved its antioxidant and antibacterial properties. Overall, the obtained results demonstrate the appropriateness of the produced membrane for wound healing applications.
Display omitted
•A new asymmetric membrane was produced through electrospinning.•The top layer, composed by SF and PCL, reproduces the features of epidermis layer.•The SF_HA_THY bottom layer mimics the properties of the dermis layer.•THY incorporation granted antimicrobial and antioxidant properties to bottom layer.•The EAM membrane demonstrated auspicious properties to be used as wound dressing.
Display omitted
•The bioactive molecules’ delivery into the wound site improves the healing process.•The nanofibers possess attractive properties to act as drug delivery system.•The antimicrobial ...molecules loaded into nanofibers to avoid infections are described.•The bioactive molecules loaded into nanofibers to assist healing process are listed.•The changes induced on nanofibers’ structural/biological properties are overviewed.
Nowadays, despite the intensive research performed in the area of skin tissue engineering, the treatment of skin lesions remains a big challenge for healthcare professionals. In fact, none of the wound dressings currently used in the clinic is capable of re-establishing all the native features of skin. An ideal wound dressing must confer protection to the wound from external microorganisms, chemical, and physical aggressions, as well as promote the healing process by stimulating the cell adhesion, differentiation, and proliferation. In recent years different types of wound dressings (such as films, hydrocolloids, hydrogels, micro/nano fibers) have been developed. Among them, electrospun nanofibrous membranes due to their intrinsic properties like high surface area-to-volume ratio, porosity and structural similarity with the skin extracellular matrix have been regarded as highly promising for wound dressings applications. Additionally, the nanofibers available in these membranes can act as drug delivery systems, which prompted the incorporation of biomolecules within their structure to prevent skin infections as well as improve the healing process. In this review, examples of different bioactive molecules that have been loaded on polymeric nanofibers are presented, highlighting the antibacterial biomolecules (e.g. antibiotics, silver nanoparticles and natural extracts-derived products) and the molecules capable of enhancing the healing process (e.g. growth factors, vitamins, and anti-inflammatory molecules).
Display omitted
Macroscale delivery systems that can be locally implanted on the tumor tissue as well as avoid all the complications associated to the systemic delivery of therapeutics have captured ...researchers’ attention, in recent years. Particularly, the microneedle-based devices can be used to efficiently deliver both small and macro-molecules, like chemotherapeutics, proteins, and genetic material, along with nanoparticle-based anticancer therapies. Such capacity prompted the application of microneedle devices for the development of new anticancer vaccines that can permeate the tumor tissue and simultaneously improve the effectiveness of therapeutic agents.
Based on the promising results demonstrated by the microneedle systems in the local administration of anticancer therapeutics, this review summarizes the different microneedle formulations developed up to now aimed for application on cancer therapy (mphasizing those produced with polymers). Additionally, the microneedles’ general properties, type of therapeutic approach and its main advantages are also highlighted.
PDF
