The engineering of future generations of nanodelivery systems aims at the creation of multifunctional vectors endowed with improved circulation, enhanced targeting and responsiveness to the ...biological environment. Moving past purely bio-inert systems, researchers have begun to create nanoparticles capable of proactively interacting with the biology of the body. Nature offers a wide-range of sources of inspiration for the synthesis of more effective drug delivery platforms. Because the nano-bio-interface is the key driver of nanoparticle behavior and function, the modification of nanoparticles’ surfaces allows the transfer of biological properties to synthetic carriers by imparting them with a biological identity. Modulation of these surface characteristics governs nanoparticle interactions with the biological barriers they encounter. Building off these observations, we provide here an overview of virus- and cell-derived biomimetic delivery systems that combine the intrinsic hallmarks of biological membranes with the delivery capabilities of synthetic carriers. We describe the features and properties of biomimetic delivery systems, recapitulating the distinctive traits and functions of viruses, exosomes, platelets, red and white blood cells. By mimicking these biological entities, we will learn how to more efficiently interact with the human body and refine our ability to negotiate with the biological barriers that impair the therapeutic efficacy of nanoparticles.
Cancer treatment still represents a formidable challenge, despite substantial advancements in available therapies being made over the past decade. One major issue is poor therapeutic efficacy due to ...lack of specificity and low bioavailability. The progress of nanotechnology and the development of a variety of nanoplatforms have had a significant impact in improving the therapeutic outcome of chemotherapeutics. Nanoparticles can overcome various biological barriers and localize at tumor site, while simultaneously protecting a therapeutic cargo and increasing its circulation time. Despite this, due to their synthetic origin, nanoparticles are often detected by the immune system and preferentially sequestered by filtering organs. Exosomes have recently been investigated as suitable substitutes for the shortcomings of nanoparticles due to their biological compatibility and particularly small size (i.e., 30-150 nm). In addition, exosomes have been found to play important roles in cell communication, acting as natural carriers of biological cargoes throughout the body. This review aims to highlight the use of exosomes as drug delivery vehicles for cancer and showcases the various attempts used to exploit exosomes with a focus on the delivery of chemotherapeutics and nucleic acids.
Nanoparticle-based drug delivery systems have been synthesized from a wide array of materials. The therapeutic success of these platforms hinges upon their ability to favorably interact with the ...biological environment (both systemically and locally) and recognize the diseased target tissue. The immune system, composed of a highly coordinated organization of cells trained to recognize foreign bodies, represents a key mediator of these interactions. Although components of this system may act as a barrier to nanoparticle (NP) delivery, the immune system can also be exploited to target and trigger signaling cues that facilitate the therapeutic response stemming from systemic administration of NPs. The nano-bio interface represents the key facilitator of this communication exchange, where the surface properties of NPs govern their
in vivo
fate. Cell membrane-based biomimetic nanoparticles have emerged as one approach to achieve targeted drug delivery by actively engaging and communicating with the biological milieu. In this review, we will highlight the relationship between these biomimetic nanoparticles and the immune system, emphasizing the role of tuning the nano-bio interface in the immunomodulation of diseases. We will also discuss the therapeutic applications of this approach with biomimetic nanoparticles, focusing on specific diseases ranging from cancer to infectious diseases. Lastly, we will provide a critical evaluation on the current state of this field of cell membrane-based biomimetic nanoparticles and its future directions in immune-based therapy.
In the field of oncology research, a deeper understanding of tumor biology has shed light on the role of environmental conditions surrounding cancer cells. In this regard, targeting the tumor ...microenvironment has recently emerged as a new way to access this disease. In this work, a novel extracellular matrix (ECM)-targeting nanotherapeutic was engineered using a lipid-based nanoparticle chemically linked to an inhibitor of the ECM-related enzyme, lysyl oxidase 1 (LOX), that inhibits the crosslinking of elastin and collagen fibers. We demonstrated that, when the conjugated vesicles were loaded with the chemotherapeutic epirubicin, superior inhibition of triple negative breast cancer (TNBC) cell growth was observed both in vitro and in vivo. Moreover, in vivo results displayed prolonged survival, minimal cytotoxicity, and enhanced biocompatibility compared to free epirubicin and epirubicin-loaded nanoparticles. This all-in-one nano-based ECM-targeting chemotherapeutic may provide a key-enabling technology for the treatment of TNBC.
A major challenge in regenerative medicine is to improve therapeutic cells' delivery and targeting using an efficient and simple protocol. Mesenchymal stem cells (MSC) are currently employed for the ...treatment of inflammatory-based diseases, due to their powerful immunosoppressive potential. Here we report a simple and versatile method to transiently overexpress the hyaluronic acid (HA) receptor, CD44, on MSC membranes, to improve their homing potential towards an inflammatory site without affecting their behavior. The effect of HA-coatings on murine MSC was functionally determined both, in vitro and in vivo as a consequence of the transient CD44 overexpression induced by HA. Data obtained from the in vitro migration assay demonstrated a two-fold increase in the migratory potential of HA-treated MSC compared to untreated cells. In an LPS-induced inflamed ear murine model, HA-treated MSC demonstrated a significantly higher inflammatory targeting as observed at 72 hrs as compared to untreated cells. This increased accumulation for HA-treated MSC yielded a substantial reduction in inflammation as demonstrated by the decrease in the expression of pro-inflammatory markers and by the induction of a pro-regenerative environment.
Abstract This report describes a novel, one-pot synthesis of hybrid nanoparticles formed by a nanostructured inorganic silica core and an organic pH-responsive hydrogel shell. This easy-to-perform, ...oil-in-water emulsion process synthesizes fluorescently-doped silica nanoparticles wrapped within a tunable coating of cationic poly(2-diethylaminoethyl methacrylate) hydrogel in one step. Transmission electron microscopy and dynamic light scattering analysis demonstrated that the hydrogel-coated nanoparticles are uniformly dispersed in the aqueous phase. The formation of covalent chemical bonds between the silica and the polymer increases the stability of the organic phase around the inorganic core as demonstrated by thermogravimetric analysis. The cationic nature of the hydrogel is responsible for the pH buffering properties of the nanostructured system and was evaluated by titration experiments. Zeta-potential analysis demonstrated that the charge of the system was reversed when transitioned from acidic to basic pH and vice versa . Consequently, small interfering RNA (siRNA) can be loaded and released in an acidic pH environment thereby enabling the hybrid particles and their payload to avoid endosomal sequestration and enzymatic degradation. These nanoparticles, loaded with specific siRNA molecules directed towards the transcript of the membrane receptor CXCR4, significantly decreased the expression of this protein in a human breast cancer cell line (i.e., MDA-MB-231). Moreover, intravenous administration of siRNA-loaded nanoparticles demonstrated a preferential accumulation at the tumor site that resulted in a reduction of CXCR4 expression.
Inflammation and Cancer: In Medio Stat Nano Molinaro, Roberto; Corbo, Claudia; Livingston, Megan ...
Current medicinal chemistry,
01/2018, Letnik:
25, Številka:
34
Journal Article
Recenzirano
Odprti dostop
Cancer treatment still remains a challenge due to the several limitations of currently used chemotherapeutics, such as their poor pharmacokinetics, unfavorable chemical properties, as well as ...inability to discriminate between healthy and diseased tissue. Nanotechnology offered potent tools to overcome these limitations. Drug encapsulation within a delivery system permitted i) to protect the payload from enzymatic degradation/ inactivation in the blood stream, ii) to improve the physicochemical properties of poorly water-soluble drugs, like paclitaxel, and iii) to selectively deliver chemotherapeutics to the cancer lesions, thus reducing the off-target toxicity, and promoting the intracellular internalization. To accomplish this purpose, several strategies have been developed, based on biological and physical changes happening locally and systemically as a consequence of tumorigenesis. Here, we will discuss the role of inflammation in the different steps of tumor development and the strategies based on the use of nanoparticles that exploit the inflammatory pathways in order to selectively target the tumor-associated microenvironment for therapeutic and diagnostic purposes.
Nanoparticles have seen considerable popularity as effective tools for drug delivery. However, non-specific targeting continues to remain a challenge. Recently, biomimetic nanoparticles have emerged ...as an innovative solution that exploits biologically-derived components to improve therapeutic potential. Specifically, cell membrane proteins extracted from various cells (i.e., leukocytes, erythrocytes, platelets, mesenchymal stem cells, cancer) have shown considerable promise in bestowing nanoparticles with increased circulation and targeting efficacy. Traditional nanoparticles can be detected and removed by the immune system which significantly hinders their clinical success. Biomimicry has been proposed as a promising approach to overcome these limitations. In this review, we highlight the current trends in biomimetic nanoparticles and describe how they are being used to increase their chemotherapeutic effect in cancer treatment.
Nanoparticles have considerable potential for cancer imaging and therapy due to their small size and prolonged circulation. However, biological barriers can impede the delivery of a sufficient dose ...of a drug to the target site, thereby also resulting in the accumulation of toxic compounds within healthy tissues, and systemic toxicity. Multistage nanovectors (MSV) preferentially accumulate on inflamed endothelium, and can thus serve as carriers for drugs and nanoparticles. Herein, we describe the loading of free (i.e., melittin) and nano-encapsulated (i.e., doxorubicin-loaded micelles) drugs into MSV, and report the impact of surface charge and pore size on drug loading. For both drug formulations, negatively charged MSV (i.e., oxidized) with larger pores were shown to retain higher concentrations of payloads compared to positively charged (i.e., APTES-modified) MSV with small pores. Treatment of human umbilical vein endothelial cells (HUVEC) with melittin-loaded MSV (MEL@MSV) resulted in an 80% reduction in cell viability after 3 days. Furthermore, MEL@MSV conjugated with antivascular endothelial growth factor receptor 2 (VEGFR2) antibodies displayed preferential targeting and delivery of MEL to activated HUVEC expressing VEGFR2. Treatment of HUVEC and MCF7 cells with doxorubicin-loaded micelles (DOXNP@MSV) resulted in a 23% and 47% reduction in cell viability, respectively. Taken together, these results demonstrate increased loading of a payload in oxidized, large pore MSV, and effective delivery of free and nano-encapsulated drugs to endothelial and cancer cells.
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