Drug Vehicle Research Articles

Boosting Natural Killer Cell Therapies in Glioblastoma Multiforme Using Supramolecular Cationic Inhibitors of Heat Shock Protein 90.

Allogeneic natural killer (aNK) cell adoptive therapy has the potential to dramatically impact clinical outcomes of glioblastoma multiforme (GBM). However, in order to exert therapeutic activity, NK cells require tumor expression of ligands for activating receptors, such as MHC Class I peptide A/B (MICA/B) and ULBPs. Here, we describe the use of a blood–brain barrier (BBB) permissive supramolecular cationic drug vehicle comprising an inhibitor of the chaperone heat shock protein 90 (Hsp90), which sustains a cytotoxic effect on GBM cells, boosts the expression of MICA/B and ULBPs on the residual population, and augments the activity of clinical-grade aNK cells (GTA002). First, we identify Hsp90 mRNA transcription and gain of function as significantly upregulated in GBM compared to other central nervous system tumors. Through a rational chemical design, we optimize a radicicol supramolecular prodrug containing cationic excipients, SCI-101, which displays >2-fold increase in relative BBB penetration compared to less cationic formulations in organoids, in vitro. Using 2D and 3D biological models, we confirm SCI-101 sustains GBM cytotoxicity 72 h after drug removal and induces cell surface MICA/B protein and ULBP mRNA up to 200% in residual tumor cells compared to the naked drug alone without augmenting the shedding of MICA/B, in vitro. Finally, we generate and test the sequential administration of SCI-101 with a clinical aNK cell therapy, GTA002, differentiated and expanded from healthy umbilical cord blood CD34+ hematopoietic stem cells. Using a longitudinal in vitro model, we demonstrate >350% relative cell killing is achieved in SCI-101–treated cell lines compared to vehicle controls. In summary, these data provide a first-of-its-kind BBB-penetrating, long-acting inhibitor of Hsp90 with monotherapy efficacy, which improves response to aNK cells and thus may rapidly alter the treatment paradigm for patients with GBM.

Poloxamer 407-Based Thermosensitive Emulgel as a Novel Formulation Providing a Controlled Release of Oil-Soluble Pharmaceuticals-Ibuprofen Case Study.

This article covers the design and evaluation of a novel drug vehicle: a thermosensitive, injectable, high-oil-content (50% w/w) emulgel providing a controlled release of lipophilic pharmaceuticals. Different vegetable (castor, canola, olive, peanut, grapeseed, linseed), mineral (paraffin) and semisynthetic (isopropyl myristate, oleic acid) oils were screened for ibuprofen (IBU) solubility and for their capacity for high-shear emulsification in a 17% (w/w) aqueous solution of poloxamer 407. Chosen emulgels were subject to a rheological evaluation, a syringeability test (TA.XT texture analyser; 2 mL syringe; 18 G, 20 G and 22 G needles) and a drug release study (48 h; cellulose membrane; 0.05 mol/L phosphate buffer at pH 7.4). Castor oil turned out to be an optimal component for IBU incorporation. Blank and drug-loaded castor oil emulgels were susceptible to administration via a syringe and needle, with the absolute injection force not exceeding 3 kg (29.4 N). The drug release test revealed dose-dependent, quasi-linear kinetics, with up to 44 h of controlled, steady, linear release. The results indicate the significant potential of high-oil-content, oil-in-water thermosensitive emulgel formulations as vehicles for the controlled release of lipophilic APIs.

Synthesis of water dispersible and biocompatible nanodiamond composite via photocatalytic surface grafting of zwitterionic polymers for intracellular delivery of DOX

As a member of nano-carbon compound, nanodiamonds (ND) with diverse structure, small size and relative low toxicity has been extensively explored for different applications especially as delivery vehicles for drugs. However, surface functionalization of ND with polymers is still required to overcome their poor water dispersibility and improve drug delivery performance. In this work, we reported a simple photocatalytic atom transfer radical polymerization (ATRP) method for surface functionalization of ND by using FeBr3 as the photoredox catalyst. Owing to the introduction of water dispersible 2-methacryloyloxyethyl phosphorylcholine (MPC), resultant NDs-MPC displayed improved water dispersibility and low toxicity. The anticancer agent DOX could be loaded on NDs-MPC efficiently and controlled release from ND-P-DOX complexes. The cell viability and cell imaging results demonstrated that DOX can be transported into cells and maintained its corresponding therapeutic effect. More importantly, as compared with traditional ATRP, photocatalytic ATRP could not only operate under rather mild conditions but also could avoid utilization of expensive and toxic agents. Considered the advantages of photocatalytic ATRP and ND, the method developed in this work could be a promising strategy for fabrication of multifunctional ND-based composites for different applications.

Chitosan-covered calcium phosphate particles as a drug vehicle for delivery to the eye

Formulations on the base of an inhibitor of angiotensin-converting enzyme, enalaprilat, were prepared by the inclusion of the drug into calcium phosphate (CaP)-particles in situ, followed by the covering of the particles with 5 kDa chitosan or 72 kDa glycol chitosan and cross-linking with sodium tripolyphosphate. Physicochemical characterization of the resulted hybrid particles was conducted using dynamic light scattering, as well as scanning and transmission electron microscopy. Enalaprilat-containing particles had a mean hydrodynamic diameter 180 nm and 260 nm and ζ-potential +7 mV and +16 mV for 5 kDa and 72 kDa chitosans, respectively. In vivo studies showed that enalaprilat within particles stayed longer in the tear fluid after single instillation and caused a significantly pronounced and prolonged decrease of intraocular pressure in rabbits, especially in the case of CaP-particles, covered by glycol chitosan. Thus, such formulations demonstrate potential as prospective therapeutic agents for the treatment of eye diseases.

First-principles studies on two-dimensional B3O3 adsorbent as a potential drug delivery platform for TEPA anticancer drug.

The remarkable properties of pristine B3O3 nanosheet as a nanocarrier for adsorption and desorption of TEPA anticancer drug for designing potential drug delivery platform were investigated using periodic DFT calculations. We studied the adsorption energy of all stable complexes formed between the drug molecule and B3O3 in gas and aqueous phases along with electronic structure analysis of complexes. Different adsorption configurations were studied for drug/B3O3 complexes, including the interaction of the C atom of the triangular ring, O atom in the TEPA drug with the B atom in B3O3, and indirect drug interaction the middle of the R1 ring cavity of the B3O3 nanosheet. The take-up of TEPA prompts a substantial change of 68.13% in the band gap (Eg) of the B3O3 nanosheet in the most stable complex. The present study results affirmed the application of B3O3 nanosheet as a potential vehicle for TEPA drugs in the treatment of cancerous tissues.

Uptake of oxidative stress-mediated extracellular vesicles by vascular endothelial cells under low magnitude shear stress

Extracellular vesicles (EVs) are increasingly used as delivery vehicles for drugs and bioactive molecules, which usually require intravascular administration. The endothelial cells covering the inner surface of blood vessels are susceptible to the shear stress of blood flow. Few studies demonstrate the interplay of red blood cell-derived EVs (RBCEVs) and endothelial cells. Thus, the phagocytosis of EVs by vascular endothelial cells during blood flow needs to be elucidated. In this study, red blood cell-derived extracellular vesicles (RBCEVs) were constructed to investigate endothelial cell phagocytosis in vitro and animal models. Results showed that low magnitude shear stress including low shear stress (LSS) and oscillatory shear stress (OSS) could promote the uptake of RBCEVs by endothelial cells in vitro. In addition, in zebrafish and mouse models, RBCEVs tend to be internalized by endothelial cells under LSS or OSS. Moreover, RBCEVs are easily engulfed by endothelial cells in atherosclerotic plaques exposed to LSS or OSS. In terms of mechanism, oxidative stress induced by LSS is part of the reason for the increased uptake of endothelial cells. Overall, this study shows that vascular endothelial cells can easily engulf EVs in areas of low magnitude shear stress, which will provide a theoretical basis for the development and utilization of EVs-based nano-drug delivery systems in vivo.

Silk fibroin hydrogels induced and reinforced by acidic calcium phosphate – A simple way of producing bioactive and drug-loadable composites for biomedical applications

Silk fibroin (SF) hydrogels have attracted extensive interest in biomedical applications due to their biocompatibility and wide availability. However, their generally poor mechanical properties limit their utility. Here, injectable, ready-to-use SF-based composites, simultaneously induced and reinforced by acidic calcium phosphates, were prepared via a dual-paste system requiring no complex chemical/physical treatment. The composite was formed by mixing a monocalcium phosphate monohydrate paste with a β-tricalcium phosphate/SF paste. The conformational transition of SF in an acidic environment forms continuous networks, and the acidic calcium phosphate, brushite and monetite, formed simultaneously in the networks during mixing. The composites displayed a partly elastomeric compression behavior, with mechanical properties increasing with an increasing calcium phosphate and β-sheet content at the lower calcium phosphate contents evaluated (22.2–36.4 wt%). While the stiffness was still relatively low, the materials presented a high elasticity and ductility, and no failure at stresses in the range of failure stresses of trabecular bone. Furthermore, the calcium phosphate confers bioactivity to the material, and the composites with a promising in vitro cell response also showed potential as drug vehicles, using vancomycin as a model drug. These dual-paste systems exhibit potential utility in biomedical applications, such as bone void fillers and drug vehicles.

Microencapsulated Isoniazid-Loaded Metal-Organic Frameworks for Pulmonary Administration of Antituberculosis Drugs.

Tuberculosis (TB) is an infectious disease that causes a great number of deaths in the world (1.5 million people per year). This disease is currently treated by administering high doses of various oral anti-TB drugs for prolonged periods (up to 2 years). While this regimen is normally effective when taken as prescribed, many people with TB experience difficulties in complying with their medication schedule. Furthermore, the oral administration of standard anti-TB drugs causes severe side effects and widespread resistances. Recently, we proposed an original platform for pulmonary TB treatment consisting of mannitol microspheres (Ma MS) containing iron (III) trimesate metal–organic framework (MOF) MIL-100 nanoparticles (NPs). In the present work, we loaded this system with the first-line anti-TB drug isoniazid (INH) and evaluated both the viability and safety of the drug vehicle components, as well as the cell internalization of the formulation in alveolar A549 cells. Results show that INH-loaded MOF (INH@MIL-100) NPs were efficiently microencapsulated in Ma MS, which displayed suitable aerodynamic characteristics for pulmonary administration and non-toxicity. MIL-100 and INH@MIL-100 NPs were efficiently internalized by A549 cells, mainly localized in the cytoplasm. In conclusion, the proposed micro-nanosystem is a good candidate for the pulmonary administration of anti-TB drugs.

The first-principles study of BC3 nanosheet as the delivery vehicle for 6-mercaptopurine drug

In this study, the potential applications of perfect boron carbide (BC3) nanosheet and single-vacancy defect BC3 nanosheets (SVBC3-B and SVBC3-C), as the drug delivery vehicle for 6-mercaptopurine (6-MP), are investigated based on the calculation of the density functional theory (DFT). The interactions of the 6-MP drug with the BC3 nanosheet, SVBC3-B and SVBC3-C are simulated in the gas phase, water solvent and acidic solvent, respectively. The results demonstrated that the 6-MP drug tends to adsorb parallel on the surface of the BC3 nanosheet, and the adsorption energy on SVBC3-B is the largest, followed by the perfect BC3. The interactions between the 6-MP drug and the perfect BC3 nanosheet, SVBC3-B and SVBC3-C will be weakened in a water solvent. Furthermore, the interaction force between the 6-MP drug and the perfect BC3 nanosheet or SVBC3-B nanosheet in an acidic solvent is more significant than that in a water solvent, which is not conducive to separating the 6-MP drug from the two kinds of BC3 nanosheets. But, the adsorption energy of the 6-MP drug on SVBC3-C in the acidic solvent is much lesser than that in the water solvent, which indicates that the 6-MP drug can be easily separated from SVBC3-C in the acidic environment. The PH value of cancer tissue is just acidic, which provides an ideal environment for separating 6-MP. Generally, the results confirmed the possibility of SVBC3-C as a delivery vehicle for the 6-MP drug.

Smart Vitamin Micelles as Cancer Nanomedicines for Enhanced Intracellular Delivery of Doxorubicin.

Chemotherapy is one of the most effective treatments for cancer. However, intracellular delivery of many anticancer drugs is hindered by their hydrophobicity and low molecular weight. Here, we describe highly biocompatible and biodegradable amphiphilic vitamin conjugates comprising hydrophobic vitamin E and hydrophilic vitamin B labeled with dual pH and glutathione-responsive degradable linkages. Vitamin-based micelles (vitamicelles), formed by self-assembly in aqueous solutions, were optimized based on their stability after encapsulation of doxorubicin (DOX). The resulting vitamicelles have great potential as vehicles for anticancer drugs because they show excellent biocompatibility (>94% after 48 h of incubation) and rapid biodegradability (>90% after 2.5 h). Compared with free DOX, DOX-loaded vitamicelles showed a markedly enhanced anticancer effect as they released the drug rapidly and inhibited drug efflux out of cells efficiently. By exploiting these advantages, this study not only provides a promising strategy for circumventing existing challenges regarding the delivery of anticancer drugs but also extends the utility of current DOX-induced chemotherapy.

Hydroxyurea-loaded Fe3O4/SiO2/chitosan-g-mPEG2000 nanoparticles; pH-dependent drug release and evaluation of cell cycle arrest and altering p53 and lincRNA-p21 genes expression.

Carbohydrate polymers were widely used in pharmaceuticals and drug delivery systems due to their biodegradability and biocompatibility. Among them, chitosan (Cs) has been considered in many new drug delivery systems. Poly(ethylene glycol) as a hydrophilic polymer can increase the solubility and stealth functions of nanocarriers. The Fe3O4 nanoparticles functionalized with polymers act as non-toxic drug vehicles for tumor targeting under external magnetic fields. In present study, the Fe3O4/SiO2-NH2 nanoparticles were prepared and then functionalized with methoxy-PEGylated chitosan (Cs-g-mPEG2000) and the hydroxyurea (HU) was loaded on this nanoparticles. The structure, crystallinity, and morphology of HU/Fe3O4/SiO2/Cs-g-mPEG2000 were determined using spectroscopic and electron microscopy analysis. Encapsulation efficiency of HU and the percentage of loading and release rate at different pH values at 37°C were examined. Maximum drug release was observed at pH = 7.4. According to TEM results, the nanoparticle sizes were between 18 and 157nm. The cytotoxicity effect of HU-loaded nanoparticles against MCF-7 human breast cancer cell was evaluated using MTT assay and cell cycle arrest analysis. The inhibitory concentration (IC50) values were 249 and 85μg/mL on the MCF-7 cell line compared to the control group in 24h and 96h, respectively. In addition, the expression of p53 and lincRNA-P21 genes in treated cells and control group was assessed using real-time PCR, and the results showed that the ratio of p53 expression to lincRNA-P21 in MCF-7 cells was significantly increased (P < 0.05). The cell cycle arrested in the S-phase and the population of cells increased 1.3-fold compared to the control group.

Synergistic chemo-photothermal cancer therapy of pH-responsive polymeric nanoparticles loaded IR825 and DTX with charge-reversal property

IR825 is a kind of near-infrared (NIR) small molecule cyanine dye and has distinct near-infrared absorbance and excellent thermal conversion performance. Due to poor stability and insufficient therapy efficacy, various nano-systems have been developed as delivery vehicles for NIR dyes to improve their application in tumor treatment. Herein, we developed an intelligent polymer drug vehicle (Mal-PAH-PEG-DMMA/ poly (ethylene imine) – poly(ε-caprolactone) block polymers, MPPD/PEI-PCL) based on pH-responsive charge-reversal to deliver docetaxel (DTX) and photosensitizer (IR825) for chemo-photothermal combination therapy (MPPD@IR825/DTX NPs). MPPD@IR825/DTX NPs could undergo charge conversion in a slightly acidic microenvironment (pH 6.8), resulted in strong electrostatic repulsion to withdraw the shell of the polymer nanoparticles (MPPD), enhanced cellular uptake and increased drug release. MPPD@IR825/DTX NPs demonstrated nanoscale in size with good mono-dispersity and stability, triggered DTX release in response to acid environment and NIR stimulation, in the same time providing excellent photothermal conversion efficiency. In vitro and In vivo experiments confirmed that charge-reversal polymeric nanoparticles improved antitumor efficiency in 4T1 tumor cell modal than non-charge-reversal polymeric nanoparticles. Furthermore, in comparison with chemotherapy or photothermal therapy in a single treatment mode, chemo-photothermal combination therapy of MPPD@IR825/DTX NPs with laser irradiation showed highly efficient tumor ablation. In addition, the polymeric nanoparticles exhibited good biocompatibility and safety. Therefore, the design of charge-reversal polymeric nanoparticles (MPPD@IR825/DTX NPs) provides a new strategy and promising application for targeting and synergistic chemo-photothermal combination therapy.

Advances and prospective applications of 3D food printing for health improvement and personalized nutrition.

Three-dimensional food printing (3DFP) uses additive manufacturing concepts to fabricate customized designed products with food ingredients in powder, liquid, dough, or paste presentations. In some cases, it uses additives, such as hydrocolloids, starch, enzymes, and antibrowning agents. Chocolate, cheese, sugar, and starch-based materials are among the most used ingredients for 3DFP, and there is a broad and growing interest in meat-, fruit-, vegetable-, insect-, and seaweed-based alternative raw materials. Here, we reviewed the most recent published information related to 3DFP for novel uses, including personalized nutrition and health-oriented applications, such as the use of 3D-printed food as a drug vehicle, and four-dimensional food printing (4DFP). We also reviewed the use of this technology in aesthetic food improvement, which is the most popular use of 3DFP recently. Finally, we provided a prospective and perspective view of this technology. We also reflected on its multidisciplinary character and identified aspects in which social and regulatory affairs must be addressed to fulfill the promises of 3DFP in human health improvement.

Temperature-sensitive properties of occluded hydration centers in direct hexagonal (HI) mesophases

Temperature-induced structural transformations of a direct hexagonal mesophase were investigated by SAXS, rheology, DSC, and NMR. The investigated mesophase region consists of two distinct direct hexagonal structures. The primary structure, detected at lower water content (33.0–39.0 wt%, 25 °C), is oriented as a bidiscontinuous assembly; it is composed of "occluded hydration centers" (OHCs) and direct surfactant-oil aggregates. The secondary structure, detected at higher water content (39.5–42.5 wt% water, 25 °C), is composed of an unbound water continuous phase and direct surfactant-oil aggregates.The OHCs within the bidiscontinuous mesophase were found to enhance the mesophase's order (correlation length (ξ)) and storage modulus (G′). The content of the unbound water occluded within the OHCs is temperature dependent, due to the ethoxylates’ water binding properties. At temperatures below 18 °C, the water in the bidiscontinuous mesophase (<39.0 wt% water) remains bound, resulting in a decreased mesophase order (correlation length (ξ)) and storage modulus (G′). Elevated temperatures increase the unbound water content, causing the unbound water domains to swell. Above the critical swelling point, the unbound water domains interlink to form a continuous phase, reducing the systems’ range order (ξ) and the storage modulus (G′).Better understanding the temperature dependence of the direct hexagonal mesophase enables mapping of the critical factors affecting the controlled delivery vehicles for non-bioavailable drugs.

Self-Assembled Nanosized Vehicles from Amino Acid-Based Amphiphilic Polymers with Pendent Carboxyl Groups for Efficient Drug Delivery.

Developing safe and efficient delivery vehicles for chemotherapeutic drugs has been a long-standing demanding. Amino acid-based polymers are promising candidates to address this challenge due to their excellent biocompatibility and biodegradation. Herein, a series of well-defined amphiphilic block copolymers were prepared by PET-RAFT polymerization of N-acryloyl amino acid monomers. By altering monomer types and the block ratio of the copolymers, the copolymers self-assembled into nanostructures with various morphologies, including spheres, rod-like, fibers, and lamellae via hydrophobic and hydrogen bonding interactions. Significantly, the nanoparticles (NPs) assembled from amphiphilic block copolymers poly(N-acryloyl-valine)-b-poly(N-acryloyl-aspartic acid) (PV-b-PD) displayed an appealing cargo loading efficiency (21.8-32.6%) for a broad range of drugs (paclitaxel, doxorubicin (DOX), cisplatin, etc.) due to strong interactions. The DOX-loaded PV-b-PD NPs exhibited rapid cellular uptake (within 1 min) and a great therapeutic performance. These drug delivery systems provide new insights for regulating the controlled morphologies and improving the efficiency of drug delivery.

The personalized application of biomaterials based on age and sexuality specific immune responses

Although biomaterials are widely utilized in clinics, it still follows the “one-fits-all” strategy. Biological variables such as age and sexuality have an impact on the host immune response and are not fully considered in the practice guidelines of the biomaterial implantation. In this study, we investigated the immuno-material interactions of six commonly used biomaterials (agarose, alginate, chitosan, CMC, GelMA and collagen type I) and constructed a population (with different ages and sexes) based transcriptome atlas. Protein and polysaccharide-based biomaterials elicited distinctive immune responses that protein-based materials preferred the NKT pathway to activate innate and adaptive immune response, whereas polysaccharide-based materials activated the cDCs to present antigen. The atlas further revealed the sex/age-related variabilities on the immune response followed by the polysaccharide treatment. As for sex bias, alginate and agarose stimulation significantly increased the proportion of naive CD4+ T cells in the female group, accompanied by the Th1 differentiation tendency, compared to the male group. Age-biased transcript showed alginate and chitosan would impair the extracellular matrix remodeling and up-regulate the apoptosis process in the elderly groups, compared to the young group. More attentions on the ingredient, age and sexuality effect of biomaterial implants should be paid during the clinical practice, especially for the polysaccharide-based materials. This experimental result is of great significance for the selection of biomaterials, particularly the blood contact materials, such as vessel or cardiac device, drug vehicles and hemostatic materials.

Halloysite-Based Nanosystems for Biomedical Applications

AbstractHalloysite nanotubes (HNTs) are hollow clay nanotubes in the nanometer size range, made up of double-layered aluminum silicate mineral layers. HNTs represent an extremely versatile, safe, and biocompatible nanomaterial, used in a wide range of applications in biomedicine and nanomedicine. For example, they are used as transporters for the controlled release of drugs or genes, in tissue engineering, in the isolation of stem cells and cancer cells, and in bioimaging. Consequently, the assessment of the biocompatibility of HNTs has acquired considerable importance. In recent years, HNT composites have attracted attention due to their improved biocompatibility, compared to HNTs, suggesting potential for applications in tissue engineering or as vehicles for drugs or genes. In this review, recent advances in the application of HNTs and HNT composites in biomedicine are discussed to provide a valuable guide to scientists in the design and development of viable, functional bio-devices for biomedical applications.

Targeted Drug Delivery for Cardiovascular Disease: Modeling of Modulated Extracellular Vesicle Release Rates.

Invasive and medical therapy has led to major improvements in cardiovascular disease management, but important challenges remain open. The discovery of a nano-sized system of extracellular vesicles (EVs) is opening new possibilities for reprogramming malfunctioning cells and indicates that EVs can be employed in therapeutic biomedical applications as engineered drug vehicles. Molecular communication (MC) has applications for treating cells with directed drug delivery, employing special targeting transmembrane proteins. In this paper, we propose a novel drug delivery system for cardiovascular diseases using an EV-mediated MC platform and exemplify the potential use in hypertrophic cardiomyopathy. We utilize intracellular calcium signaling as a natural mediator of EVs released from synthetic cells and model the release rate. We propose to use the cells as a therapeutic release system with a control signal input which modulates the EVs release rate as the output signal. We also study the frequency domain of the proposed model and estimate the transfer function of the therapeutic release system model numerically where the root-mean-square error for two separate estimated output signals are 0.0353 and 0.0124. The proposed EV-mediated targeted drug delivery system can make breakthroughs in future healthcare, in cardiovascular and other diseases where targeting is required.

Increased photoluminescence and photodynamic therapy efficiency of hydroxyapatite-β-cyclodextrin-methylene blue@carbon powders with the favor of hydrogen bonding effect.

To meet the requirements of theranostics with diagnosis and treatment, photodynamic-based therapy is simultaneously enabled with the incorporation of methylene blue (MB) as imaging agent and photosensitizer in core-shell structured drug vehicles. Citrate-modified hydroxyapatite (HAp) powders are first grafted with β-cyclodextrin (CD), then combined with MB molecules through electrostatic interactions, and finally encapsulated with carbon shells through hydro-thermal carbonization of glucose to prepare HAp-CD-MB@C powders. Processing parameters of carbonization temperature, glucose addition, reaction time and CD addition are varied to prepare drug carriers with modulated crystallite degrees and photo-physical properties. Increased crystallite sizes of HAp are accompanied with the formation of C=O, C=C and C-OH groups in carbon shell, endowing sustainable release behaviors of MB through carbonous structures. High photoluminescence intensities are fairly related with red-shifted vibration peaks of groups in tightly combined MB molecules through hydrogen bonds. This hydrogen bonding effect is significantly increased for HAp-CD-MB@C140 with the splitting of CH3-involved vibration peaks in infrared spectra, which causes increase in photoluminescence intensity and four-fold increase in generation ratio of singlet oxygen. The present studies shed light on preparation of core-shell structured drug carriers, modulation of aggregate states of MB molecules, enhancement of photo-physical properties and improvement of generation ratio of singlet oxygen during photodynamic-based therapy.

Exosomes as A Next-Generation Diagnostic and Therapeutic Tool in Prostate Cancer

Extracellular vesicles (EVs) have brought great momentum to the non-invasive liquid biopsy procedure for the detection, characterization, and monitoring of cancer. Despite the common use of PSA (prostate-specific antigen) as a biomarker for prostate cancer, there is an unmet need for a more specific diagnostic tool to detect tumor progression and recurrence. Exosomes, which are EVs that are released from all cells, play a large role in physiology and pathology, including cancer. They are involved in intercellular communication, immune function, and they are present in every bodily fluid studied—making them an excellent window into how cells are operating. With liquid biopsy, EVs can be isolated and analyzed, enabling an insight into a potential therapeutic value, serving as a vehicle for drugs or nucleic acids that have anti-neoplastic effects. The current application of advanced technology also points to higher-sensitivity detection methods that are minimally invasive. In this review, we discuss the current understanding of the significance of exosomes in prostate cancer and the potential diagnostic value of these EVs in disease progression.