Search Results (20)

Glioblastoma (GBM), the most common, invasive, and chemoresistant form of adult primary brain cancer, is characterized by rapid cell proliferation, local invasiveness, and resistance to chemotherapy (e.g., temozolomide (TMZ)) and radiation therapy. Curcumin, a bioactive polyphenol derived from Curcuma longa, has exhibited exceptional anti-cancer properties, including anti-proliferative, pro-apoptotic, anti-inflammatory, and anti-angiogenic activities in a wide range of cancer models, including GBM. However, the clinical application of curcumin has been seriously limited by several challenges, including low water solubility, low bioavailability, rapid systemic clearance, and poor blood–brain barrier (BBB) penetration. To overcome these challenges, several nanocarrier systems to produce nanocurcumin have been developed, including liposomes, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, and micelles. These nanoformulations improve the solubility, stability, systemic circulation, and target-directed delivery of curcumin to glioma cells, thereby resulting in a high level of accumulation in the glioma microenvironment. On the other hand, this work is devoted to the potential of curcumin and nanocurcumin for the treatment of GBM. The article provides a detailed review of the major molecular targets of curcumin, such as NF-κB, STAT3, PI3K/AKT/mTOR, and p53 signaling pathways, as well as recent advancements in nanotechnology-based delivery platforms that improve drug delivery across the BBB and their possible clinical translation. We also include a thorough examination of the issues, limitations, and potential opportunities associated with the clinical advancement of curcumin-based therapeutics for GBM. Full article

Polymers and polymer composites offer versatile possibilities for engineering the physico-chemical properties of materials on micro- and macroscopic scales. This review provides an overview of polymeric and polymer-decorated particles that can serve as drug-delivery vectors: linear polymers, star polymers, diblock-copolymer micelles, polymer-grafted nanoparticles, polymersomes, stealth liposomes, microgels, and biomolecular condensates. The physico-chemical interactions between the delivery vectors and biological cells range from chemical interactions on the molecular scale to deformation energies on the particle scale. The focus of this review is on the structure and elastic properties of these particles, as well as their circulation in blood and cellular uptake. Furthermore, the effects of polymer decoration in vivo (e.g., of glycosylated plasma membranes, cortical cytoskeletal networks, and naturally occurring condensates) on drug delivery are discussed. Full article

Detecting circulating tumor cells has exhibited great significance in treating cancers since its concentration is an index strongly associated with the development and transfer of the tumor. However, the present commercial method for CTC detection is still expensive, because special antibodies and complicated devices must be used for cell separation and imaging. Hence, it is quite necessary to apply alternative materials and methods to decrease the cost of CTC detection. In this article, we coated a cellulose acetate membrane with nanoparticles formed by the polymerization of melamine and furfural, creating a surface with nanoscale roughness for the highly efficient capture of the sparse CTCs in a blood sample. Subsequently, the CTCs on the surface can be quantitatively detected by colorimetry with the aid of a COF-based nanozyme. The detection limit (LOD) can be as low as 3 cells/mL, which is the lowest LOD among the colorimetric methods to our knowledge. Considering the low cost of fabricating the membrane for CTC capture and the robustness of nanozymes compared with natural enzymes, this CTC detection approach displays great potential to decrease the financial burden of commercial CTC detection. Full article

Lipid nanoparticles (LNPs) are spherical vesicles composed of ionizable lipids that are neutral at physiological pH. Despite their benefits, unmodified LNP drug delivery systems have substantial drawbacks, including a lack of targeted selectivity, a short blood circulation period, and in vivo instability. lipid–polymer hybrid nanoparticles (LPHNPs) are the next generation of nanoparticles, having the combined benefits of polymeric nanoparticles and liposomes. LPHNPs are being prepared from both natural and synthetic polymers with various techniques, including one- or two-step methods, emulsification solvent evaporation (ESE) method, and the nanoprecipitation method. Varieties of LPHNPs, including monolithic hybrid nanoparticles, core–shell nanoparticles, hollow core–shell nanoparticles, biomimetic lipid–polymer hybrid nanoparticles, and polymer-caged liposomes, have been investigated for various drug delivery applications. However, core–shell nanoparticles having a polymeric core surrounded by a highly biocompatible lipid shell are the most commonly explored LPHNPs for the treatment of various diseases. In this review, we will shed light on the composition, methods of preparation, classification, surface functionalization, release mechanism, advantages and disadvantages, patents, and clinical trials of LPHNPs, with an emphasis on core–shell-structured LPHNPs. Full article

Quercetin is a hydrophobic molecule with short blood circulation times and instability. The development of a nano-delivery system formulation of quercetin may increase its bioavailability, resulting in greater tumor suppressing effects. Triblock ABA type polycaprolactone-polyethylenglycol- polycaprolactone (PCL-PEG-PCL) copolymers have been synthetized using ring-opening polymerization of caprolactone from PEG diol. The copolymers were characterized by nuclear magnetic resonance (NMR), diffusion-ordered NMR spectroscopy (DOSY), and gel permeation chromatography (GPC). The triblock copolymers self-assembled in water forming micelles consisting of a core of biodegradable polycaprolactone (PCL) and a corona of polyethylenglycol (PEG). The core-shell PCL-PEG-PCL nanoparticles were able to incorporate quercetin into the core. They were characterized by dynamic light scattering (DLS) and NMR. The cellular uptake efficiency of human colorectal carcinoma cells was quantitatively determined by flow cytometry using nanoparticles loaded with Nile Red as hydrophobic model drug. The cytotoxic effect of quercetin-loaded nanoparticles was evaluated on HCT 116 cells, showing promising results. Full article

Currently, particular interest among the scientific community is focused on exploring the use of exosomes for several pharmaceutical and biomedical applications. This is due to the identification of the role of exosomes as an excellent intercellular communicator by delivering the requisite cargo comprising of functional proteins, metabolites and nucleic acids. Exosomes are the smallest extracellular vesicles (EV) with sizes ranging from 30–100 nm and are derived from endosomes. Exosomes have similar surface morphology to cells and act as a signal transduction channel between cells. They encompass different biomolecules, such as proteins, nucleic acids and lipids, thus rendering them naturally as an attractive drug delivery vehicle. Like the other advanced drug delivery systems, such as polymeric nanoparticles and liposomes to encapsulate drug substances, exosomes also gained much attention in enhancing therapeutic activity. Exosomes present many advantages, such as compatibility with living tissues, low toxicity, extended blood circulation, capability to pass contents from one cell to another, non-immunogenic and special targeting of various cells, making them an excellent therapeutic carrier. Exosome-based molecules for drug delivery are still in the early stages of research and clinical trials. The problems and clinical transition issues related to exosome-based drugs need to be overcome using advanced tools for better understanding and systemic evaluation of exosomes. In this current review, we summarize the most up-to-date knowledge about the complex biological journey of exosomes from biogenesis and secretion, isolation techniques, characterization, loading methods, pharmaceutical and therapeutic applications, challenges and future perspectives of exosomes. Full article

The development of biomimetic drug delivery systems for biomedical applications has attracted significant research attention. As the use of cell membrane as a surface coating has shown to be a promising platform for several disease treatments. Cell-membrane-coated nanoparticles exhibit enhanced immunocompatibility and prolonged circulation time. Herein, human red blood cell (RBC) membrane-cloaked nanoparticles with enhanced targeting functionality were designed as a targeted nanotheranostic against cancer. Naturally, derived human RBC membrane modified with targeting ligands coated onto polymeric nanoparticle cores containing both chemotherapy and imaging agent. Using epithelial cell adhesion molecule (EpCAM)-positive MCF-7 breast cancer cells as a disease model, the nature-inspired targeted theranostic human red blood cell membrane-coated polymeric nanoparticles (TT-RBC-NPs) platform was capable of not only specifically binding to targeted cancer cells, effectively delivering doxorubicin (DOX), but also visualizing the targeted cancer cells. The TT-RBC-NPs achieved an extended-release profile, with the majority of the drug release occurring within 5 days. The TT-RBC-NPs enabled enhanced cytotoxic efficacy against EpCAM positive MCF-7 breast cancer over the non-targeted NPs. Additionally, fluorescence images of the targeted cancer cells incubated with the TT-RBC-NPs visually indicated the increased cellular uptake of TT-RBC-NPs inside the breast cancer cells. Taken together, this TT-RBC-NP platform sets the foundation for the next-generation stealth theranostic platforms for systemic cargo delivery for treatment and diagnostic of cancer. Full article

Lactosomes™ are biocompatible nanoparticles that can be used for cancer tissue imaging and drug delivery. Lactosomes are polymeric micelles formed by the self-assembly of biodegradable amphiphilic block copolymers composed of hydrophilic polysarcosine and hydrophobic poly-L-lactic acid chains. The particle size can be controlled in the range of 20 to 100 nm. Lactosomes can also be loaded with hydrophobic imaging probes and photosensitizers, such as indocyanine green. Indocyanine green-loaded lactosomes are stable for long-term circulation in the blood, allowing for accumulation in cancer tissues. Such lactosomes function as a photosensitizer, which simultaneously enables fluorescence diagnosis and photodynamic therapy. This review provides an overview of lactosomes with respect to molecular design, accumulation in cancer tissue, and theranostics applications. The use of lactosomes can facilitate the treatment of cancers in unresectable tissues, such as glioblastoma and head and neck cancers, which can lead to improved quality of life for patients with recurrent and unresectable cancers. We conclude by describing some outstanding questions and future directions for cancer theranostics with respect to clinical applications. Full article

Nanoparticles are excellent platforms for several biomedical applications, including cancer treatment. They can incorporate different molecules to produce combinations of chemotherapeutic agents, radionuclides, and targeting molecules to improve the therapeutic strategies against cancer. These specific nanosystems are designed to have minimal side effects on healthy cells and better treatment efficacy against cancer cells when compared to chemotherapeutics, external irradiation, or targeted radiotherapy alone. In colorectal cancer, some metal and polymeric nanoparticle platforms have been used to potentialize external radiation therapy and targeted drug delivery. Polymeric nanoparticles, liposomes, albumin-based nanoparticles, etc., conjugated with PEG and/or HLA, can be excellent platforms to increase blood circulation time and decrease side effects, in addition to the combination of chemo/radiotherapy, which increases therapeutic efficacy. Additionally, radiolabeled nanoparticles have been conjugated to target specific tissues and are mainly used as agents for diagnosis, drug/gene delivery systems, or plasmonic photothermal therapy enhancers. This review aims to analyze how nanosystems are shaping combinatorial therapy and evaluate their status in the treatment of colorectal cancer. Full article

Photothermal nanoparticles can be used for non-antibiotic-based eradication of infectious biofilms, but this may cause collateral damage to tissue surrounding an infection site. In order to prevent collateral tissue damage, we encapsulated photothermal polydopamine-nanoparticles (PDA-NPs) in mixed shell polymeric micelles, composed of stealth polyethylene glycol (PEG) and pH-sensitive poly(β-amino ester) (PAE). To achieve encapsulation, PDA-NPs were made hydrophobic by electrostatic binding of indocyanine green (ICG). Coupling of ICG enhanced the photothermal conversion efficacy of PDA-NPs from 33% to 47%. Photothermal conversion was not affected by micellar encapsulation. No cytotoxicity or hemolytic effects of PEG-PAE encapsulated PDA-ICG-NPs were observed. PEG-PAE encapsulated PDA-ICG-NPs showed good penetration and accumulation in a Staphylococcus aureus biofilm. Penetration and accumulation were absent when nanoparticles were encapsulated in PEG-micelles without a pH-responsive moiety. PDA-ICG-NPs encapsulated in PEG-PAE-micelles found their way through the blood circulation to a sub-cutaneous infection site after tail-vein injection in mice, yielding faster eradication of infections upon near-infrared (NIR) irradiation than could be achieved after encapsulation in PEG-micelles. Moreover, staphylococcal counts in surrounding tissue were reduced facilitating faster wound healing. Thus, the combined effect of targeting and localized NIR irradiation prevented collateral tissue damage while eradicating an infectious biofilm. Full article

Polymer nanoparticles are a promising approach for cancer treatment and detection, due to their biocompatibility, biodegradability, targeting capabilities, capacity for drug loading and long blood circulation time. This study aims to evaluate the impact of poly (styrene–acrylic acid) latex particles on colorectal and cervical cancer cells for anti-tumor efficiency. Latex particles were synthesized by a surfactant-free radical emulsion polymerization process and the obtained polymer particles were characterized in terms of size, size distribution, morphology using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and electrokinetic property (i.e., zeta potential). Human colorectal and cervical cancer, and normal cell lines, were then treated with different concentrations of poly (styrene–acrylic acid) latex particles. The cell morphology changes were pointed out using an optical microscope and the nanoparticles’ (NPs) cell cytotoxicity was evaluated using MTT assay. The obtained results showed that poly (styrene–acrylic acid) latex particles are effective against colorectal and cervical cancer cells if treated with an appropriate particle concentration for 48 h. In addition, it showed that normal cells are the least affected by this treatment. This indicates that these NPs are safe as a drug delivery carrier when used at a low concentration. Full article

Ang-(1-9) peptide is a bioactive vasodilator peptide that prevents cardiomyocyte hypertrophy in vitro and in vivo as well as lowers blood pressure and pathological cardiovascular remodeling; however, it has a reduced half-life in circulation, requiring a suitable carrier for its delivery. In this work, hybrid nanoparticles composed of polymeric nanoparticles (pNPs) based on Eudragit^® E/Alginate (EE/Alg), and gold nanospheres (AuNS), were developed to evaluate their encapsulation capacity and release of Ang-(1-9) under different experimental conditions. Hybrid pNPs were characterized by dynamic light scattering, zeta potential, transmission and scanning electron microscopy, size distribution, and concentration by nanoparticle tracking analysis. Nanometric pNPs, with good polydispersity index and colloidally stable, produced high association efficiency of Ang-(1-9) and controlled release. Finally, the treatment of neonatal cardiomyocytes in culture with EE/Alg/AuNS 2% + Ang-(1-9) 20% pNPs decreased the area and perimeter, demonstrating efficacy in preventing norepinephrine-induced cardiomyocyte hypertrophy. On the other hand, the incorporation of AuNS did not cause negative effects either on the cytotoxicity or on the association capacity of Ang-(1-9), suggesting that the hybrid carrier EE/Alg/AuNS pNPs could be used for the delivery of Ang-(1-9) in the treatment of cardiovascular hypertrophy. Full article

Light-sensitive polymeric micelles have recently emerged as promising drug delivery systems for spatiotemporally controlled release of payload at target sites. Here, we developed diazonaphthoquinone (DNQ)-conjugated micellar nanoparticles that showed a change in polarity of the micellar core from hydrophobic to hydrophilic under UV light, releasing the encapsulated anti-cancer drug, doxetaxel (DTX). The micelles exhibited a low critical micelle concentration and high stability in the presence of bovine serum albumin (BSA) solution due to the hydrophobic and π–π stacking interactions in the micellar core. Cell studies showed enhanced cytotoxicity of DTX-loaded micellar nanoparticles upon irradiation. The enhanced stability would increase the circulation time of the micellar nanoparticles in blood, and enhance the therapeutic effectiveness for cancer therapy. Full article

Drug nanoformulations hold remarkable promise for the efficient delivery of therapeutics to a disease site. Unfortunately, artificial nanocarriers, mostly liposomes and polymeric nanoparticles, show limited applications due to the unfavorable pharmacokinetics and rapid clearance from the blood circulation by the reticuloendothelial system (RES). Besides, many of them have high cytotoxicity, low biodegradability, and the inability to cross biological barriers, including the blood brain barrier. Extracellular vesicles (EVs) are novel candidates for drug delivery systems with high bioavailability, exceptional biocompatibility, and low immunogenicity. They provide a means for intercellular communication and the transmission of bioactive compounds to targeted tissues, cells, and organs. These features have made them increasingly attractive as a therapeutic platform in recent years. However, there are many obstacles to designing EV-based therapeutics. In this review, we will outline the main hurdles and limitations for therapeutic and clinical applications of drug loaded EV formulations and describe various attempts to solve these problems. Full article

The binding of plasma proteins to a drug carrier alters the circulation of nanoparticles (NPs) in the bloodstream, and, as a consequence, the anticancer efficiency of the entire nanoparticle drug delivery system. We investigate the possible interaction and the interaction mechanism of a polymeric drug delivery system based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers (pHPMA) with the most abundant proteins in human blood plasma—namely, human serum albumin (HSA), immunoglobulin G (IgG), fibrinogen (Fbg), and apolipoprotein (Apo) E4 and A1—using a combination of small-angle X-ray scattering (SAXS), analytical ultracentrifugation (AUC), and nuclear magnetic resonance (NMR). Through rigorous investigation, we present evidence of weak interactions between proteins and polymeric nanomedicine. Such interactions do not result in the formation of the protein corona and do not affect the efficiency of the drug delivery. Full article