Research Progress on the Degradation of Organic Pollutants in Water by Activated Persulfate Using Biochar-Loaded Nano Zero-Valent Iron.

Biochar (BC) is a new type of carbon material with a high specific surface area, porous structure, and good adsorption capacity, which can effectively adsorb and enrich organic pollutants. Meanwhile, nano zero-valent iron (nZVI) has excellent catalytic activity and can rapidly degrade organic pollutants through reduction and oxidation reactions. The combined utilization of BC and nZVI can not only give full play to their advantages in the adsorption and catalytic degradation of organic pollutants, but also help to reduce the agglomeration of nZVI, thus improving its efficiency in water treatment and providing strong technical support for water resources protection and environmental quality improvement. This article provides a detailed introduction to the preparation method and characterization technology, reaction mechanism, influencing factors, and specific applications of BC and nZVI, and elaborates on the research progress of BC-nZVI in activating persulfate (PS) to degrade organic pollutants in water. It has been proven experimentally that BC-nZVI can effectively remove phenols, dyes, pesticides, and other organic pollutants. Meanwhile, in response to the existing problems in current research, this article proposes future research directions and challenges, and summarizes the application prospects and development trends of BC-nZVI in water treatment. In summary, BC-nZVI-activated PS is an efficient technology for degrading organic pollutants in water, providing an effective solution for protecting water resources and improving environmental quality, and has significant application value.

Research Progress of Ozone/Peroxymonosulfate Advanced Oxidation Technology for Degrading Antibiotics in Drinking Water and Wastewater Effluent: A Review.

Nowadays, antibiotics are widely used, increasing the risk of contamination of the water body and further threatening human health. The traditional water treatment process is less efficient in degrading antibiotics, and the advanced oxidation process (AOPs) is cleaner and more efficient than the traditional biochemical degradation process. The combined ozone/peroxymonosulfate (PMS) advanced oxidation process (O3/PMS) based on sulfate radical (SO4•-) and hydroxyl radical (•OH) has developed rapidly in recent years. The O3/PMS process has become one of the most effective ways to treat antibiotic wastewater. The reaction mechanism of O3/PMS was reviewed in this paper, and the research and application progress of the O3/PMS process in the degradation of antibiotics in drinking water and wastewater effluent were evaluated. The operation characteristics and current application range of the process were summarized, which has a certain reference value for further research on O3/PMS process.

A nanoemulsion targeting adipose hypertrophy and hyperplasia shows anti-obesity efficiency in female mice.

Obesity often leads to severe medical complications. However, existing FDA-approved medications to combat obesity have limited effectiveness in reducing adiposity and often cause side effects. These medications primarily act on the central nervous system or disrupt fat absorption through the gastrointestinal tract. Adipose tissue enlargement involves adipose hyperplasia and hypertrophy, both of which correlate with increased reactive oxygen species (ROS) and hyperactivated X-box binding protein 1 (XBP1) in (pre)adipocytes. In this study, we demonstrate that KT-NE, a nanoemulsion loaded with the XBP1 inhibitor KIRA6 and α-Tocopherol, simultaneously alleviates aberrant endoplasmic reticulum stress and oxidative stress in (pre)adipocytes. As a result, KT-NE significantly inhibits abnormal adipogenic differentiation, reduces lipid droplet accumulation, restricts lipid droplet transfer, impedes obesity progression, and lowers the risk of obesity-associated non-alcoholic fatty liver disease in female mice with obesity. Furthermore, diverse administration routes of KT-NE impact its in vivo biodistribution and contribute to localized and/or systemic anti-obesity effectiveness.

Antioxidant nanoemulsion loaded with latanoprost enables highly effective glaucoma treatment.

Glaucoma is the third leading cause of blindness worldwide and is primarily characterized by elevated intraocular pressure (IOP). Common risk factors such as age, myopia, ocular trauma, and hypertension all increase the risk of elevated IOP. Prolonged high IOP not only causes physiological discomfort like headaches, but also directly damages retinal cells and leads to retinal ischemia, oxidative imbalance, and accumulation of reactive oxygen species (ROS) in the retina. This oxidative stress causes the oxidation of proteins and unsaturated lipids, leading to peroxide formation and exacerbating retinal damage. While current clinical treatments primarily target reducing IOP through medication or surgery, there are currently no effective methods to mitigate the retinal cell damage associated with glaucoma. To address this gap, we developed a novel nanoemulsion to co-delivery latanoprost and α-tocopherol (referred to as LA@VNE later) that prolongs ocular retention and enhances retinal permeability through localized administration. By encapsulating latanoprost, an IOP-lowering drug, and α-tocopherol, a potent antioxidant, we effectively reduced ROS accumulation (>1.5-fold in vitro and 2.5-fold in vivo), retinal ganglion cell (RGC) apoptosis (>9 fold), and inflammatory cell infiltration (>1.6 fold). Our approach showed strong biocompatibility and significant potential for clinical translation, providing a promising platform for the treatment of glaucoma.

Neutrophil hitchhiking for drug delivery to the bone marrow.

Pharmaceuticals have been developed for the treatment of a wide range of bone diseases and disorders, but suffer from problematic delivery to the bone marrow. Neutrophils are naturally trafficked to the bone marrow and can cross the bone marrow-blood barrier. Here we report the use of neutrophils for the targeted delivery of free drugs and drug nanoparticles to the bone marrow. We demonstrate how drug-loaded poly(lactic-co-glycolic acid) nanoparticles are taken up by neutrophils and are then transported across the bone marrow-blood barrier to boost drug concentrations in the bone marrow. We demonstrate application of this principle to two models. In a bone metastasis cancer model, neutrophil delivery is shown to deliver cabazitaxel and significantly inhibit tumour growth. In an induced osteoporosis model, neutrophil delivery of teriparatide is shown to significantly increase bone mineral density and alleviate osteoporosis indicators.

Arginine Supplementation Targeting Tumor-Killing Immune Cells Reconstructs the Tumor Microenvironment and Enhances the Antitumor Immune Response.

The tumor microenvironment (TME) is characterized by several immunosuppressive factors, of which weak acidity and l-arginine (l-arg) deficiency are two common features. A weak acidic environment threatens the survival of immune cells, and insufficient l-arg will severely restrain the effect of antitumor immune responses, both of which affect the efficiency of cancer treatments (especially immunotherapy). Meanwhile, l-arg is essential for tumor progression. Thus, two strategies, l-arg supplementation and l-arg deprivation, are developed for cancer treatment. However, these strategies have the potential risk of promoting tumor growth and impairing immune responses, which might lead to a paradoxical therapeutic effect. It is optimal to limit the l-arg availability of tumor cells from the microenvironment while supplying l-arg for immune cells. In this study, we designed a multivesicular liposome technology to continuously supply alkaline l-arg, which simultaneously changed the acidity and l-arg deficiency in the TME, and by selectively knocking down the CAT-2 transporter, l-arg starvation of tumors was maintained while tumor-killing immune cells were enriched in the TME. The results showed that our strategy promoted the infiltration and activation of CD8+ T cells in tumor, increased the proportion of M1 macrophages, inhibited melanoma growth, and prolonged survival. In combination with anti-PD-1 antibody, our strategy reversed the low tumor response to immune checkpoint blockade therapy, showing a synergistic antitumor effect. Our work provided a reference for improving the TME combined with regulating nutritional competitiveness to achieve the sensitization of immunotherapy.

Rational administration sequencing of immunochemotherapy elicits powerful anti-tumor effect.

As a research hotspot, immune checkpoint inhibitors (ICIs) is often combined with other therapeutics in order to exert better clinical efficacy. To date, extensive laboratory and clinical investigations into the combination of ICIs and chemotherapy have been carried out, demonstrating augmented effectiveness and broad application prospects in anti-tumor therapy. However, the administration of these two treatment modalities is usually randomized or fixed to a given chronological order. Nevertheless, the pharmacological effect of drug is closely related to its exposure behavior in vivo, which may consequently affect the synergistic outcomes of a combined therapy. In this study, we prepared a lipid nanoparticle encapsulating docetaxel (DTX-VNS), and associated it with the immune checkpoint inhibitor anti-PD-1 antibody (αPD-1) for the treatment of malignant tumors. To identify the optimum timing and sequencing for chemotherapy and immunotherapy, we designed three administration regimes, including the simultaneous delivery of DTX-VNS and αPD-1(DTX-VNS@αPD-1), DTX-VNS delivery before (DTX-VNS plus αPD-1) or post (αPD-1 plus DTX-VNS) PD-1 blockade with an interval of two days. Analysis from mass spectrometry, multi-factor detection and other techniques indicated that DTX-VNS plus αPD-1 initiated a powerful anti-tumor response in multiple tumor models, contributing to a remarkably reshaped tumor microenvironment landscape, which may attribute to the maximum therapeutic additive effects arise from a concomitant exposure of DTX-VNS and αPD-1 at the tumor site. By profiling the exposure kinetics of nanoparticles and αPD-1 in vivo, we defined the administration schedule with utmost therapeutic benefits, which may provide a valuable clinical reference for the rational administration of immunochemotherapy.

An analysis of the biopharmaceutical behaviour of proton pump inhibitors with different physicochemical properties.

At present, little information on the biopharmaceutical behaviour of proton pump inhibitors (PPIs) describing their absorption and biodistribution in vivo has been reported because the extreme instability of PPIs in the gastrointestinal environment makes it difficult to analyze such behaviour. In this work, a modified rat in situ intestinal perfusion model was employed to investigate absorption in the gastrointestinal tract and subsequent biodistribution of several PPIs (ilaprazole, esomeprazole and rabeprazole), which have different physicochemical properties. Our data indicated that PPIs exhibited significantly enhanced absorption rates in the whole intestine, including the duodenum, jejunum, ileum and colon, corresponding to the increase in the oil-water partition coefficient (LogP). PPIs and corresponding salt types showed no obvious differences in absorption, implying that solubility changes in the PPI have little effect on its absorption in the gastrointestinal tract. Among these PPIs, ilaprazole presented a more stable intestinal absorption behaviour, as well as more distribution and longer residence time in the stomach by HPLC-MS/MS analysis and radioactivity counts after 14C radiolabelling. These results may be useful information for PPI optimization and oral formulation design.

The study of intestinal absorption and biodistribution in vivo of proton pump inhibitors.

The major therapeutic strategy for acid-related gastrointestinal diseases in clinic is to reduce the excretion of gastric acid by oral administration of proton-pump inhibitors (PPIs). However, it is quite a challenge to study the oral absorption behaviors of PPIs considering their extreme instability under gastrointestinal environment. As a result, little information has been reported on PPI oral absorption so far, hindering the further development of PPI-contained oral preparations. Here, we first investigated the degradation rate of three representative PPIs, including ilaprazole, ilaprazole sodium and rabeprazole sodium. Then a modified in situ intestine absorption method in rat was established: through the temperature control by the heat exchangers, the perfusate was kept at physiological temperature only when passing through the intestine while it was maintained at 4 °C outside the intestine. Therefore PPIs could maintained sufficiently high stability under proper temperature control. Our data demonstrated that both ilaprazole and ilaprazole sodium exhibited significantly higher absorption efficiency than rabeprazole sodium did through the comparison of their apparent permeability coefficients and steady-state plasma concentrations after perfusion in the duodenum, jejunum, ileum and colon, mainly attributing to their more suitable oil-water partition coefficient. The duodenum could be the best site for the oral absorption of PPIs. Ilaprazole outperformed its sodium salt form with its stable absorption behavior in tested four intestinal segments. Furthermore, after intravenous or oral administration, ilaprazole exhibited a longer residence time and a higher accumulation in the stomach than in most of other tissues/organs. However, it was also found that the accumulation was heterogeneous and mainly located in mucosa cells of the stomach. Our further study indicated that there was no significant difference on the oral absorption efficiency of ilaprazole between female and male rats but ilaprazole underwent a faster metabolism in male rats after oral absorption. Our study provided a valuable guidance for the design of oral formulation and the optimization of PPI-contained formulations.

Selective Intratumoral Drug Release and Simultaneous Inhibition of Oxidative Stress by a Highly Reductive Nanosystem and Its Application as an Anti-tumor Agent.

Excessive oxidative stress is always associated with the serious side effects of chemotherapy. In the current study, we developed a vitamin E based strongly reductive nanosystem to increase the loading efficiency of docetaxel (DTX, DTX-VNS), reduce its side toxicity and enhance the antitumor effect. Methods: We used Förster Resonance Energy Transfer (FRET) to reveal the in vivo and in vitro fate of DTX-VNS over time. All FRET images were observed using the Maestro imaging system (CRI, Inc., Woburn, MA) and Fluo-View software (Olympus LX83-FV3000). Results: Through FRET analyzing, we found that our nanosystem showed a selective rapider release of drugs in tumors compared to normal organs due to the higher levels of ROS in tumor cells than normal cells, and the accumulation of DTX at tumor sites in the DTX-VNS group was also notably more than that in the Taxotere group after 24 h injection. Meanwhile, DTX-VNS had a prominently stronger anti-tumor effect in various models than Taxotere, and had a synergistic effect of immunotherapy. Conclusions: Our work presented a useful reference for clinical exploration of the in vivo behavior of nanocarriers (DTX-VNS), inhibition oxidative stress and selective release of drugs at tumor sites, thus reducing the side effects and enhancing the anti-tumor effects.

Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death.

Immunogenic cell death (ICD)-associated immunogenicity can be evoked through reactive oxygen species (ROS) produced via endoplasmic reticulum (ER) stress. In this study, we generate a double ER-targeting strategy to realize photodynamic therapy (PDT) photothermal therapy (PTT) immunotherapy. This nanosystem consists of ER-targeting pardaxin (FAL) peptides modified-, indocyanine green (ICG) conjugated- hollow gold nanospheres (FAL-ICG-HAuNS), together with an oxygen-delivering hemoglobin (Hb) liposome (FAL-Hb lipo), designed to reverse hypoxia. Compared with non-targeting nanosystems, the ER-targeting naosystem induces robust ER stress and calreticulin (CRT) exposure on the cell surface under near-infrared (NIR) light irradiation. CRT, a marker for ICD, acts as an 'eat me' signal to stimulate the antigen presenting function of dendritic cells. As a result, a series of immunological responses are activated, including CD8+ T cell proliferation and cytotoxic cytokine secretion. In conclusion, ER-targeting PDT-PTT promoted ICD-associated immunotherapy through direct ROS-based ER stress and exhibited enhanced anti-tumour efficacy.

Temperature-controlled, phase-transition ultrasound imaging-guided photothermal-chemotherapy triggered by NIR light.

Recently, nano-sized ultrasound contrast agents encapsulating drugs for cancer diagnosis and therapy have attracted much attention. However, the ultrasound signal of these agents is too weak to obtain an ideal ultrasound imaging effect. Furthermore, conventional ultrasound contrast agents with strong echo signal are not suitable for drug delivery against cancer because of their large size. To circumvent this problem, phase-transition ultrasound contrast agents are believed to be an excellent choice. Methods: Liposomes co-encapsulating doxorubicin (DOX), hollow gold nanospheres (HAuNS), and perfluorocarbon (PFC) were synthesized by film dispersion method. The morphology, particle size, and stability of these liposomes (DHPL) were investigated. The photothermal effect, drug release, particle size change, cytotoxicity, and ultrasound imaging were studied by using the near infrared (NIR) light. Furthermore, tumor accumulation of DHPL was observed by in vivo fluorescence imaging and the antitumor effect was verified in a 4T1 tumor model. Results: The nanosystem displayed a homogeneous size distribution (~200 nm) and an efficient light-to-heat conversion effect under 808 nm NIR laser irradiation. The nanometer size enabled considerable accumulation of DHPL in the tumor sites. The localized hyperthermia resulting from the photothermal effect of HAuNS could trigger the size transformation of DHPL followed by significant DOX release. Due to the gasification of PFC, a remarkably enhanced ultrasound signal was detected. DHPL also exhibited a prominent photothermally reinforced chemotherapeutic effect under the control of NIR light both in vitro and in vivo. Importantly, no systemic toxicity was observed by DHPL treatment. Conclusion: In this study, we fabricated multi-functional perfluorocarbon liposomes for ultrasound imaging-guided photothermal chemotherapy which have the potential to serve as a prospective cancer treatment approach.

Sustained release of anti-PD-1 peptide for perdurable immunotherapy together with photothermal ablation against primary and distant tumors.

Immune checkpoint PD-1/PD-L1 blockade has emerged as a successful immunotherapy strategy for treating several types of malignant tumors. A constant and proper drug concentration during the treatment is important because the long-term activation of the immune system is urgently needed to perdurably recognize and attack cancer cells for a better therapeutic effect with minimum side effects. However, practically few related studies have been reported to date. In this study, we constructed a therapeutic strategy combining PD-1 blocking with photothermal ablation for malignant tumors by co-encapsulating anti-PD-1 peptide (APP) and hollow gold nanoshell (HAuNS) into biodegradable Poly (d, l-lactic-co-glycolide) nanoparticles (APP- and HAuNS-loaded PLGA nanoparticles, AA@PN). Slow and continuous release of APP from AA@PN could be obtained from 0 to 40 days, and this release was easily accelerated by illumination with a near-infrared (NIR) laser. A clear killing effect on distant tumor cells was observed after treatment of the co-culture system of PMBCs and tumor cells with AA@PN plus an NIR laser, reflecting the activated immune response. AA@PN followed by multiple irradiations with an NIR laser showed the strongest antitumor effect, with the elimination of most primary tumors compared with other treatments, and significantly inhibited the growth of the distant uninjected primary tumors, similarly to free APP with frequent injections, which induced the longest survival time for the mice in this group.

Suppress orthotopic colon cancer and its metastasis through exact targeting and highly selective drug release by a smart nanomicelle.

The treatment of metastatic cancer is a huge challenge at the moment. Highly precise targeting delivery and drug release in tumor have always been our pursuit in cancer therapy, especially to advance cancer with metastasis, for increasing the efficacy and biosafety. We established a smart nanosized micelle, formed by tocopherol succinate (TOS) conjugated hyaluronic acid (HA) using a disulfide bond linker. The micelle (HA-SS-TOS, HSST) can highly specifically bind with CD44 receptor over-expressed tumor, and response selectively to high GSH level in the cells, inducing disulfide bond breakage and the release of the payload (paclitaxel, PTX). To predict the antitumor efficacy of the micelles more clinically, we established an orthotopic colon cancer model with high metastasis rate, which could be visualized by the luciferase bioluminescence. Our data confirmed CD44 high expression in the colon cancer cells. Highly matching between the micellar fluorescence and bioluminescence of cancer cells in intestines demonstrated an exact recognition of our micelles to orthotopic colon tumor and its metastatic cells, attributing to the mediation of CD44 receptors. Furthermore, the fluorescence of the released Nile Red from the micelles was found only in the tumor and its metastatic cells, and almost completely overlapped with the bioluminescence of the cancer cells, indicating a highly selective drug release. Our micelles presented an excellent therapeutic effect against metastatic colon cancer, and induced significantly prolonged survival time for the mice, which might become a promising nanomedicine platform for the future clinical application against advanced cancers with high CD44 receptor expression.

A photosensitive liposome with NIR light triggered doxorubicin release as a combined photodynamic-chemo therapy system.

The targeted drug delivery with the help of nanocarriers and the controlled drug release at the lesion sites are the most effective ways to enhance therapeutic efficacy and reduce side effects. Here, we built a light sensitive liposome (Her2-I&D-LSL) which was formed by a special phospholipid (PLsPC) and a hydrophobically modified photosensitizer (ICG-ODA). DOX was employed as the therapeutic drug, encapsulating in the internal phase of the liposome whose surface was modified by Her2 antibodies for recognizing tumor cells with high Her2 receptor expression. Mediated by NIR light, Her2-I&D-LSL was proved to generate sufficient ROS to realize PDT, which then triggered the release of DOX for combined chemotherapy. The ROS generation and DOX release were verified to be strictly controlled by NIR light and the proportion of ICG-ODA. Thanks to the mediation of Her2 receptor, the specific DOX release and the combination of PDT-chemotherapy triggered by NIR light, Her2-I&D-LSL showed a significant accumulation in MCF7 and SKOV3 tumors, thus leading to the strongest tumor growth inhibition effect compared to PDT alone (I-LSL) or chemotherapy alone (D-LSL). Her2-I&D-LSL also possessed a great biocompatibility due to the targeted treatment, holding promise for future cancer therapy in clinic.

Synchronous delivery of oxygen and photosensitizer for alleviation of hypoxia tumor microenvironment and dramatically enhanced photodynamic therapy.

Photosensitizer, proper laser irradiation, and oxygen are essential components for effective photodynamic therapy (PDT) in clinical cancer therapy. However, native hypoxic tumoral microenvironment is a major barrier hindering photodynamic reactions in vivo. Thus, we have prepared biocompatible liposomes by loading complexes of oxygen-carrier (hemoglobin, Hb) and photosensitizer (indocyanine green, ICG) for enhanced PDT against hypoxic tumor. Ideal oxygen donor Hb, which is an oxygen-carried protein in red blood cells, makes such liposome which provide stable oxygen supply. ICG, as a photosensitizer, could transfer energy from lasers to oxygen to generate cytotoxic reactive oxygen species (ROS) for treatment. The liposomes loading ICG and Hb (LIH) exhibited efficient tumor homing upon intravenous injection. As revealed by T2-weighted magnetic resonance imaging and immunohistochemical analysis, the intratumoral hypoxia was greatly alleviated, and the level of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in tumor was obviously down-regulated. A weak PDT efficiency was found in cells incubated in simulated hypoxia condition in vitro, while PDT effect was dramatically enhanced in LIH treated hypoxia cells under near-infrared (NIR) laser, which was mainly attributed to massive generation of ROS with sufficient oxygen supply. ROS trigger oxidative damage of tumors and induce complete suppression of tumor growth and 100% survival rate of mice, which were also in good health condition. Our work highlights a liposome-based nanomedicine that could effectively deliver oxygen to tumor and alleviate tumor hypoxia state, inducing greatly improved efficacy compared to conventional cancer PDT and demonstrates the promise of modulating unfavorable tumor microenvironment with nanotechnology to overcome limitations of cancer therapies.

Overcoming photodynamic resistance and tumor targeting dual-therapy mediated by indocyanine green conjugated gold nanospheres.

Photodynamic therapy (PDT) and photothermal therapy (PTT) have captured much attention due to the great potential to cure malignant tumor. Nevertheless, photodynamic resistance of cancer cells has limited the further efficacy of PDT. Unfortunately, the resistance mechanism and efforts to overcome the resistance still have been rarely reported so far. Here, we report a nanosystem with specific tumor targeting for combined PDT and PTT mediated by near-infrared (NIR) light, which was established by covalently conjugating indocyanine green (ICG) and TNYL peptide onto the surface of hollow gold nanospheres (HAuNS). Our nanosystem (TNYL-ICG-HAuNS) was proved to possess significantly increased light stability, reactive oxygen species (ROS) production and photothermal effect under NIR light irradiation, thus presenting a remarkably enhanced antitumor efficacy. The up-regulation of nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) in cancer cells during PDT induced a significant increase of ABCG2, NQO-1 and HIF-1α expression, causing PDT resistance of the cells. Interestingly, ABCG2 expression could almost keep a normal level in the whole PDT process mediated by TNYL-ICG-HAuNS. After repeated irradiations, TNYL-ICG-HAuNS could still produce almost constant ROS in cells while the Nrf2 expression reduced significantly. Furthermore, PDT resistance induced an obvious decrease of the internalization of free ICG, but didn't influence the cell uptake of TNYL-ICG-HAuNS. Our data explained that TNYL-ICG-HAuNS could overcome the photodynamic resistance of cancer cells, acting as a promising modality for simultaneous photothermal and photodynamic cancer therapy.

Specifically Increased Paclitaxel Release in Tumor and Synergetic Therapy by a Hyaluronic Acid-Tocopherol Nanomicelle.

Recently, interest in tumor-targeted and site-specific drug release from nanoparticles as a means of drug delivery has increased. In this study, we report a smart nanosized micelle formed by hyaluronic acid (HA) conjugated with d-α-tocopherol succinate (TOS) using a disulfide bond as the linker (HA-SS-TOS, HSST). HSST micelles can specifically bind to the CD44 receptors that are overexpressed by cancer cells. The high levels of glutathione (GSH) in tumor cells selectively break the disulfide bond linker. This effect results in the synchronous release of the payload and a TOS fragment. These two components subsequently demonstrate synergetic anticancer activity. First, we demonstrate that drug release from HSST occurs rapidly in physiological high redox conditions and inside cancer cells. Significant GSH-triggered drug release was also observed in vivo. Furthermore, an in vivo biodistribution study indicated that the HSST micelles efficiently accumulated at the tumor sites, primarily due to an enhanced permeability and retention effect and the efficient binding to the cancer cells that overexpressed the CD44 receptor. Interestingly, the synchronous release of paclitaxel (PTX) and the TOS fragment from the PTX-loaded HSST caused synergetic tumor cell killing and tumor growth inhibition. Our work presents a useful candidate for a drug delivery system that can specifically accumulate at tumor tissue, selectively release its payload and a TOS fragment, and thus display a synergetic anticancer effect.

External Magnetic Field-Enhanced Chemo-Photothermal Combination Tumor Therapy via Iron Oxide Nanoparticles.

The development of multifunctional nanoplatforms based on magnetic nanoparticles (MNPs) has attracted increasing attention. MNPs especially exhibit excellent responsiveness under the guidance of an external magnetic field (MF), resulting in tumor-specific, targeted delivery. The behavior and magnetic-targeting efficiency of MNPs largely depend on their physiochemical properties, especially the particle size; however, the optimal size range may vary across the multiple bioapplications associated with multifunctional nanoparticles. The optimal size range of nanoparticles for external MF-mediated targeted delivery has rarely been reported. In this work, we synthesized a series of monodisperse Fe3O4 nanoparticles with identical surface properties ranging in size from 10 to 310 nm, and we systematically investigated their behavior and MF-assisted antitumor efficacy. Our data indicated that smaller Fe3O4 nanoparticles exhibited greater cellular internalization, while larger Fe3O4 nanoparticles showed greater tumor accumulation. Larger Fe3O4 nanoparticles exhibited stronger magnetic responsiveness both in vitro and in vivo, which could be used to further induce increased accumulation of nanoparticles and their payload (e.g., doxorubicin) into the tumor site under the guidance of an external MF. Our work demonstrated that larger Fe3O4 nanoparticles, with a diameter of up to 310 nm, exhibited the best magnetic-targeting efficiency mediated by an external MF and the strongest antitumor efficacy from combination photothermal-chemotherapy. Our results could serve as a valuable reference for the future design of MNPs and their targeted delivery via the modulation of an external MF.

Specific Photothermal Ablation Therapy of Endometriosis by Targeting Delivery of Gold Nanospheres.

Endometriosis is difficult to treat since the side effects of the current therapeutic method and the high recurrence rate; thus, newer and safer therapeutic approaches are urgently needed. This work investigates the enhanced permeability and retention effect of CdTe quantum dots (QDs) and hollow gold nanospheres (HAuNS) in endometriosis to increase the delivery of HAuNS into lesion cells. The surface of HAuNS is successfully conjugated with a TNYL peptide that has specific affinity for the EphB4 receptor, which is a member of the Eph family of receptor tyrosine kinases. It is found that the EphB4 receptor is overexpressed in endometriosis lesions. The data indicate that both QDs and HAuNS can efficiently accumulate in endometriotic lesions through permeable vessels and the TNYL-conjugated HAuNS (TNYL-HAuNS) accumulate more via the interaction with EphB4. The specific photothermal ablation therapy based on TNYL-HAuNS significantly inhibits the growth of the endometriotic volume and induces the atrophy and degeneration of ectopic endometrium with no detectable toxicity to the normal organs. The level of TNF-α and estradiol also significantly decreases in the endometriotic lesions, indicating that the treatment enables a recovery from hormonal imbalance and inflammatory injury. This work can be a valuable reference for future endometriosis therapy.