[Chasing New Cancer Treatments: Current Status and Future Development of Boron Neutron Capture Therapy].

Boron neutron capture therapy (BNCT) is expected to be a promising next-generation cancer treatment. In 2020, Japan, which has led the research on this treatment modality, was the first country in the world to approve BNCT. The boron agents that have been clinically applied in BNCT include a caged boron compound (mercaptoundecahydrododecaborate: BSH) and a boron-containing amino acid (p-boronophenylalanine: BPA). In particular, the BPA preparation Steboronine® is the only approved drug for BNCT. However, the problem with BPA is that it is poorly retained in the tumor and has very low solubility in water. This cannot be overlooked for BNCT, which requires large amounts of boron in the tumor. The high dosage volume, together with low tumor retention, leads to reduced therapeutic efficacy and increased physical burden on the patient. In the case of BSH, its insufficient penetration into the tumor is problematic. Based on drug delivery system (DDS) technology, we have developed a next-generation boron pharmaceutical superior to Steboronine®. Our approach involves the redevelopment of BPA using innovative ionic liquid formulation technology. Here, we describe previous boron agents and introduce our recent efforts in the development of boron compounds.

Thermoresponsive lipids engineered magnetic nanoparticles for spatiotemporal delivery of hesperidin to inflammatory sites in animal model.

Thermoresponsive nanoparticles are exploited as drug-delivery vehicles that release their payload upon increment in temperature. We prepared and characterized thermoresponsive lipid-anchored folic acid engineered magnetic nanoparticles (LP-HP-FANPs) that combine receptor-based targeting and thermoresponsive sustained release of hesperidin (HP) in response to endogenous inflammation site temperature. The progressive surface engineering of NPs was validated by FTIR analysis. Our LP-HP-FANPs had a particle size of 100.5 ± 1.76 nm and a zeta potential of 14.6 ± 2.65 mV. The HP encapsulation effectiveness of LP-HP-FANPs is around 91 ± 0.78%. AFM scans indicated that our modified nanoparticles were spherical. LP-HP-FANPs exhibit increased drug release (85.8% at pH 4.0, 50.9% at pH 7.0) at 40 °C. Animal studies showed no toxicity from nanoparticles. Compared to conventional drugs and HP, LP-HP-FANPs effectively decreased paw edema, cytokine levels, and total cell recruitment in thioglycollate-induced peritonitis (p < 0.05). LP-HP-FANPs substantially decreased cytokines compared to HP, HP-FA-NPs, and the standard medication (p < 0.05, p < 0.01, and p < 0.001). These findings imply that the synthesized HP-loaded formulation (LP-HP-FANPs) may be a potential anti-inflammatory formulation for clinical development.

DDS-type near-infrared light absorber enables deeper lesion treatment in laser photothermal therapy while avoiding damage to surrounding organs.

The efficacy of drug delivery system (DDS)-type near-infrared (NIR) absorbing agents in enhancing laser photothermal therapy is widely acknowledged. Despite the acknowledged efficacy, the therapeutic advantages of photothermal therapy using DDS-type NIR-absorbing agents over simple photothermal therapy without such agents have not been fully elucidated. This study was designed to investigate two primary objectives: firstly, the ability of DDS-type NIR-absorbing agents to induce cell death at greater depths within tumors, and secondly, their capacity to minimize collateral damage to adjacent healthy organs. To investigate these objectives, we employed a combination of indocyanine green lactosome-a DDS-type NIR-absorbing agent-and a precision-controlled laser hyperthermia system. An orthotopic neuroblastoma tumor model was used to closely simulate clinical conditions. The findings revealed that photothermal therapy using the DDS-type NIR-absorbing agent not only facilitates deeper penetration of cell death within tumors but also significantly mitigates thermal damage to surrounding healthy tissues, when compared to simple phototherapy without the agent. Furthermore, the combined treatment significantly prolonged the survival periods of the animals involved. This study is the first to analyze these therapeutic efficacies using quantitative data from an orthotopic tumor animal model and substantiated the potential of DDS-type NIR-absorbing agents to deepen the therapeutic impact of photothermal therapy while safeguarding vital organs, thereby enhancing overall treatment outcomes.

Bacterial nanocellulose as a simple and tailorable platform for controlled drug release.

In this study we present a proof of concept of a simple and straightforward approach for the development of a Bacterial Nanocellulose drug delivery system (BNC-DDS), envisioning the local delivery of immunomodulatory drugs to prevent foreign body reaction (FBR). Inspired by the self-adhesion behavior of BNC upon drying, we proposed a BNC laminate entrapping commercial crystalline drugs (dexamethasone-DEX and GW2580) in a sandwich system. The stability of the bilayer BNC-DDS was evidenced by the high interfacial energy of the bilayer films, 150 ± 11 and 88 ± 7 J/m2 respectively for 2 mm- and 10-mm thick films, corresponding to an increase of 7.5 and 4.4-fold comparatively to commercial tissue adhesives. In vitro release experiments unveiled the tunability of the bilayer BNC-DDS by showing extended drug release when thicker BNC membranes were used (from 16 to 47 days and from 35 to 132 days, for the bilayer-BNC entrapping DEX and GW2580, respectively). Mathematical modeling of the release data pointed to a diffusion-driven mechanism with non-fickian behavior. Overall, the results have demonstrated the potential of this simple approach for developing BNC-drug depots for localized and sustained release of therapeutic agents over adjustable timeframes.

Dendrimer Platforms for Targeted Doxorubicin Delivery-Physicochemical Properties in Context of Biological Responses.

The unique structure of G4.0 PAMAM dendrimers allows a drug to be enclosed in internal spaces or immobilized on the surface. In the conducted research, the conditions for the formation of the active G4.0 PAMAM complex with doxorubicin hydrochloride (DOX) were optimized. The physicochemical properties of the system were monitored using dynamic light scattering (DLS), circular dichroism (CD), and fluorescence spectroscopy. The Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D) method was chosen to determine the preferential conditions for the complex formation. The highest binding efficiency of the drug to the cationic dendrimer was observed under basic conditions when the DOX molecule was deprotonated. The decrease in the zeta potential of the complex confirms that DOX immobilizes through electrostatic interaction with the carrier's surface amine groups. The binding constants were determined from the fluorescence quenching of the DOX molecule in the presence of G4.0 PAMAM. The two-fold way of binding doxorubicin in the structure of dendrimers was visible in the Isothermal calorimetry (ITC) isotherm. Fluorescence spectra and release curves identified the reversible binding of DOX to the nanocarrier. Among the selected cancer cells, the most promising anticancer activity of the G4.0-DOX complex was observed in A375 malignant melanoma cells. Moreover, the preferred intracellular location of the complexes concerning the free drug was found, which is essential from a therapeutic point of view.

Path to bacteriotherapy: From bacterial engineering to therapeutic perspectives.

The major reason for the failure of conventional therapies is the heterogeneity and complexity of tumor microenvironments (TMEs). Many malignant tumors reprogram their surface antigens to evade the immune surveillance, leading to reduced antigen-presenting cells and hindered T-cell activation. Bacteria-mediated cancer immunotherapy has been extensively investigated in recent years. Scientists have ingeniously modified bacteria using synthetic biology and nanotechnology to enhance their biosafety with high tumor specificity, resulting in robust anticancer immune responses. To enhance the antitumor efficacy, therapeutic proteins, cytokines, nanoparticles, and chemotherapeutic drugs have been efficiently delivered using engineered bacteria. This review provides a comprehensive understanding of oncolytic bacterial therapies, covering bacterial design and the intricate interactions within TMEs. Additionally, it offers an in-depth comparison of the current techniques used for bacterial modification, both internally and externally, to maximize their therapeutic effectiveness. Finally, we outlined the challenges and opportunities ahead in the clinical application of oncolytic bacterial therapies.

Hollow mesoporous calcium peroxide nanoparticles for drug-free tumor calcicoptosis therapy.

Calcium ions (Ca2+) participate in the regulation of cellular apoptosis as a second messenger. Calcium overload, which refers to the abnormal elevation of intracellular Ca2+ concentration, is a factor that can lead to cell death. Here, based on the unique biological effects of Ca2+, hollow mesoporous calcium peroxide nanoparticles (HMCPN) were developed by a facile hydrolysis-precipitation method for drug-free tumor calcicoptosis therapy. The average pore size of the optimized HMCPN17 is 6.4 nm, and the surface area is 81.3 m2/g, which enables HMCPN17 with high drug loading capability. The Ca2+ release from HMCPN17 is much faster at pH 6.8 than that at pH 7.4, which can be ascribed to the acid-triggered conversion of HMCPN17 to Ca2+ and H2O2, indicating a pH-responsive decomposition behavior of HMCPN17. The high drug loading contents of doxorubicin (DOX) and/or sorafenib (SFN) indicate that HMCPN17 can be employed as a generic drug delivery system (DDS). The in vitro and in vivo results reinforce the high calcicoptosis therapeutic efficacy of tumors by our HMCPN17 without drug loading, which can be attributed to the efficient accumulation in tumors and the ability of H2O2 and Ca2+ production at acidic TME. Our HMCPN17 has broad application prospect for construction of multi-drug-loaded composite nanomaterials with diversified functions for the treatment of tumors. STATEMENT OF SIGNIFICANCE: The combination of hollow mesoporous nanomaterials and calcium peroxide nanoparticles has a wide range of applications in the synergistic treatment of tumors. In this study, hollow mesoporous calcium peroxide nanoparticles (HMCPN) were developed based on a simple hydrolysis-precipitation method for tumor calcicoptosis therapy without drug loading. The high drug loading contents of DOX and/or SFN indicate that our HMCPN can serve as a generic DDS. The experimental results demonstrated the high calcicoptosis therapeutic efficacy of HMCPN on tumors even without drug loading.

Polymer Conjugate as the New Promising Drug Delivery System for Combination Therapy against Cancer.

This review highlights the advantages of combination therapy using polymer conjugates as drug delivery systems for cancer treatment. In this review, the specific structures and materials of polymer conjugates, as well as the different types of combination chemotherapy strategies, are discussed. Specific targeting strategies, such as monoclonal antibody therapy and small molecule ligands, are also explored. Additionally, self-assembled polymer micelles and overcoming multidrug resistance are described as potential strategies for combination therapy. The assessment of combinational therapeutic efficacy and the challenges associated with polymer conjugates are also addressed. The future outlook aims to overcome these challenges and improve the effectiveness of drug delivery systems for combination therapy. The conclusion emphasizes the potential of polymer conjugates in combination therapy while acknowledging the need for further research and development in this field.

Advance on combination therapy strategies based on biomedical nanotechnology induced ferroptosis for cancer therapeutics.

Globally, cancer is a serious health problem. It is unfortunate that current anti-cancer strategies are insufficiently specific and damage the normal tissues. There's urgent need for development of new anti-cancer strategies. More recently, increasing attention has been paid to the new application of ferroptosis and nano materials in cancer research. Ferroptosis, a condition characterized by excessive reactive oxygen species-induced lipid peroxidation, as a new programmed cell death mode, exists in the process of a number of diseases, including cancers, neurodegenerative disease, cerebral hemorrhage, liver disease, and renal failure. There is growing evidence that inducing ferroptosis has proven to be an effective strategy against a variety of chemo-resistant cancer cells. Nano-drug delivery system based on nanotechnology provides a highly promising platform with the benefits of precise control of drug release and reduced toxicity and side effects. This paper reviews the latest advances of combination therapy strategies based on biomedical nanotechnology induced ferroptosis for cancer therapeutics. Given the new chances and challenges in this emerging area, we need more attention to the combination of nanotechnology and ferroptosis in the treatment of cancer in the future.

Overcoming the High Error Rate of Composite DNA Letters-Based Digital Storage through Soft-Decision Decoding.

Composite DNA letters, by merging all four DNA nucleotides in specified ratios, offer a pathway to substantially increase the logical density of DNA digital storage (DDS) systems. However, these letters are susceptible to nucleotide errors and sampling bias, leading to a high letter error rate, which complicates precise data retrieval and augments reading expenses. To address this, Derrick-cp is introduced as an innovative soft-decision decoding algorithm tailored for DDS utilizing composite letters. Derrick-cp capitalizes on the distinctive error sensitivities among letters to accurately predict and rectify letter errors, thus enhancing the error-correcting performance of Reed-Solomon codes beyond traditional hard-decision decoding limits. Through comparative analyses in the existing dataset and simulated experiments, Derrick-cp's superiority is validated, notably halving the sequencing depth requirement and slashing costs by up to 22% against conventional hard-decision strategies. This advancement signals Derrick-cp's significant role in elevating both the precision and cost-efficiency of composite letter-based DDS.

Exploring Curcumin-Loaded Lipid-Based Nanomedicine as Efficient Targeted Therapy for Alzheimer's Diseases.

Alzheimer's disease (AD) is a neurological condition currently with 47 million people suffering from it globally. AD might have many reasons such as genetic issues, environmental factors, and Aß accumulation, which is the biomarker of the disease. Since the primary reason is unknown, there is no targeted treatment at the moment, but ongoing research aims to slow its progression by managing amyloid-beta peptide production rather than symptomatic improvement. Since phytochemicals have been demonstrated to possess antioxidant, anti-inflammatory, and neuroprotective properties, they may target multiple pathological factors and can reduce the risk of the disease. Curcumin, as a phytochemical found in turmeric known for its antioxidant, free radical scavenging properties, and as an antiamyloid in treating AD, has come under investigation. Although its low bioavailability limits its efficacy, a prominent drug delivery system (DDS) is desired to overcome it. Hence, the potency of lipid-based nanoparticles encapsulating curcumin (LNPs-CUR) is considered in this study as a promising DDS. In vivo studies in animal models indicate LNPs-CUR effectively slow amyloid plaque formation, leading to cognitive enhancement and reduced toxicity compared to free CUR. However, a deeper understanding of CUR's pharmacokinetics and safety profile is crucial before LNPs-CUR can be considered as a medicine. Future investigations may explore the combination of NPs with other therapeutic agents to increase their efficacy in AD cases. This review provides the current position of CUR in the AD therapy paradigm, the DDS suggestions for CUR, and the previous research from the point of analytical view focused on the advantages and challenges.

Chitosan-grafted folic acid decorated one-dimensional GONS: A biocompatible drug cargo for targeted co-delivery of anticancer agents.

In conventional chemotherapy, the cancer cells can become highly resilient due to a phenomenon known as multi-drug resistance (MDR). The co-delivery of chemotherapeutic agents assisted with novel nanocarrier-based targeted DDS may counter the MDR issues and subsequently improve their therapeutic efficacy. In line with this, the present work deals with the development of 1D graphene oxide nanoscrolls (GONS)-based nano delivery system for co-delivery of chemosensitizer along with the chemotherapeutic agent. Herein, the 1D GONS nanocarrier was initially functionalized with chitosan (CS) biopolymer and folic acid (FA) further to enhance their biocompatibility and target-specific co-delivery. The resultant GONS-CS-FA (GCF) nanocarriers were co-loaded with doxorubicin (DOX) and caffeic acid (CA) at different weight proportions with respect to nanocarrier and drug composition. The optimum loading efficiency of 51.14 ± 1.47 % (DOX) and 49.70 ± 1.19 % (CA) was observed for GCF: drug ratio of 2.5 with drug composition of 1:1. In vitro release at pH 5 yielded ~83 % DOX and 75 % CA, compared to ~71 % DOX and 61 % CA at pH 7.4 over 7 days, suggesting a higher and targeted drug release in the cancer microenvironment. Cytotoxicity tests revealed selective apoptosis in cancer cells (A549) while maintaining cytocompatibility with normal cells (HEK293).

Advancements in Nanosystems for Ocular Drug Delivery: A Focus on Pediatric Retinoblastoma.

The eye's complex anatomical structures present formidable barriers to effective drug delivery across a range of ocular diseases, from anterior to posterior segment pathologies. Emerging as a promising solution to these challenges, nanotechnology-based platforms-including but not limited to liposomes, dendrimers, and micelles-have shown the potential to revolutionize ophthalmic therapeutics. These nanocarriers enhance drug bioavailability, increase residence time in targeted ocular tissues, and offer precise, localized delivery, minimizing systemic side effects. Focusing on pediatric ophthalmology, particularly on retinoblastoma, this review delves into the recent advancements in functionalized nanosystems for drug delivery. Covering the literature from 2017 to 2023, it comprehensively examines these nanocarriers' potential impact on transforming the treatment landscape for retinoblastoma. The review highlights the critical role of these platforms in overcoming the unique pediatric eye barriers, thus enhancing treatment efficacy. It underscores the necessity for ongoing research to realize the full clinical potential of these innovative drug delivery systems in pediatric ophthalmology.

Double-Layered Hollow Mesoporous Cuprous Oxide Nanoparticles for Double Drug Sequential Therapy of Tumors.

Cancer stem cells (CSCs) are one of the determinants of tumor heterogeneity and are characterized by self-renewal, high tumorigenicity, invasiveness, and resistance to various therapies. To overcome the resistance of traditional tumor therapies resulting from CSCs, a strategy of double drug sequential therapy (DDST) for CSC-enriched tumors is proposed in this study and is realized utilizing the developed double-layered hollow mesoporous cuprous oxide nanoparticles (DL-HMCONs). The high drug-loading contents of camptothecin (CPT) and all-trans retinoic acid (ATRA) demonstrate that the DL-HMCON can be used as a generic drug delivery system. ATRA and CPT can be sequentially loaded in and released from CPT3@ATRA3@DL-HMCON@HA. The DDST mechanisms of CPT3@ATRA3@DL-HMCON@HA for CSC-containing tumors are demonstrated as follows: 1) the first release of ATRA from the outer layer induces differentiation from CSCs with high drug resistance to non-CSCs with low drug resistance; 2) the second release of CPT from the inner layer causes apoptosis of non-CSCs; and 3) the third release of Cu+ from DL-HMCON itself triggers the Fenton-like reaction and glutathione depletion, resulting in ferroptosis of non-CSCs. This CPT3@ATRA3@DL-HMCON@HA is verified to possess high DDST efficacy for CSC-enriched tumors with high biosafety.

Hydrodesulfurization of Dibenzothiophene: A Machine Learning Approach.

The hydrodesulfurization (HDS) process is widely used in the industry to eliminate sulfur compounds from fuels. However, removing dibenzothiophene (DBT) and its derivatives is a challenge. Here, the key aspects that affect the efficiency of catalysts in the HDS of DBT were investigated using machine learning (ML) algorithms. The conversion of DBT and selectivity was estimated by applying Lasso, Ridge, and Random Forest regression techniques. For the estimation of conversion of DBT, Random Forest and Lasso offer adequate predictions. At the same time, regularized regressions have similar outcomes, which are suitable for selectivity estimations. According to the regression coefficient, the structural parameters are essential predictors for selectivity, highlighting the pore size, and slab length. These properties can connect with aspects like the availability of active sites. The insights gained through ML techniques about the HDS catalysts agree with the interpretations of previous experimental reports.

Food diversity: its relation to children's health and consequent economic burden.

BACKGROUND: This study investigates the impact of low food diversity on the health status of children using the Dietary Diversity Score (DDS) and Dietary Serving Score (DSS) in a sub-district with the highest percentage of poor households. The economic burden of low food diversity was observed by analysing the cost of illness in the children with low food diversity. METHODS: Data from 329 children were collected. We determined the impact of DDS and DSS and other factors on the health status of children aged 2-14 years, using a probit model. The cost of illness (e.g., typhus, stomach ulcers, coughs, flu, and fever) due to low food diversity was calculated from medical registration fees, medical action costs, transportation costs, and other costs. RESULTS: The results shows that a 1% point increase in DDS or DSS potentially decreases children's health complaints by 10% and 8%, respectively. Given the current 26% prevalence of health complaints among children with low DDS, the annual economic burden reaches US$75.72 per child per household. In addition, the current 41% prevalence of children with low DDS resulted in an annual cost to the government of US$153.45 per child. CONCLUSIONS: The effect of inadequate dietary diversity on children's health is potentially high and contributes to the economic burden on households and the government.

Two-Photon-Responsive "TICT + AIE" Active Naphthyridine-BF2 Photoremovable Protecting Group: Application for Specific Staining and Killing of Cancer Cells.

The combined effects of twisted intramolecular charge transfer (TICT) and aggregation-induced emission (AIE) phenomena have demonstrated a significant influence on excited-state chemistry. These combined TICT and AIE features have been extensively utilized to enhance photodynamic and photothermal therapy. Herein, we demonstrated the synergistic capabilities of TICT and AIE phenomena in the design of the photoremovable protecting group (PRPG), namely, NMe2-Napy-BF2. This innovative PRPG incorporates TICT and AIE characteristics, resulting in four remarkable properties: (i) red-shifted absorption wavelength, (ii) strong near-infrared (NIR) emission, (iii) viscosity-sensitive emission property, and (iv) accelerated photorelease rate. Inspired by these intriguing attributes, we developed a nanodrug delivery system (nano-DDS) using our PRPG for cancer treatment. In vitro studies showed that our nano-DDS manifested effective cellular internalization, specific staining of cancer cells, high-resolution confocal imaging of cancerous cells in the NIR region, and controlled release of the anticancer drug chlorambucil upon exposure to light, leading to cancer cell eradication. Most notably, our nano-DDS exhibited a substantially increased two-photon (TP) absorption cross section (435 GM), exhibiting its potential for in vivo applications. This development holds promise for significant advancements in cancer treatment strategies.

An Icon of Painless Parker.

The discovery of two unaccredited photographs purported to be of Painless Parker occasions a discussion of the notorious "outlaw" dentist's historical significance. It is argued that social media threaten to have performance eclipse clinical skills in dentistry - a process that can be sourced to Parker's vaudevillian antics.

An injectable polyacrylamide/chitosan-based hydrogel with highly adhesive, stretchable and electroconductive properties loaded with irbesartan for treatment of myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (MIRI) significantly contributes to the high incidence of complications and mortality associated with acute myocardial infarction. Recently, injectable electroconductive hydrogels (IECHs) have emerged as promising tools for replicating the mechanical, electroconductive, and physiological characteristics of cardiac tissue. Herein, we aimed to develop a novel IECH by incorporating irbesartan as a drug delivery system (DDS) for cardiac repair. Our approach involved merging a conductive poly-thiophene derivative (PEDOT: PSS) with an injectable dual-network adhesive hydrogel (DNAH) comprising a catechol-branched polyacrylamide network and a chitosan-hyaluronic acid covalent network. The resulting P-DNAH hydrogel, benefitting from a high conducting polymer content, a chemically crosslinked network, a robust dissipative matrix, and dynamic oxidation of catechol to quinone exhibited superior mechanical strength, desirable conductivity, and robust wet-adhesiveness. In vitro experiments with the P-DNAH hydrogel carrying irbesartan (P-DNAH-I) demonstrated excellent biocompatibility by cck-8 kit on H9C2 cells and a rapid initial release of irbesartan. Upon injection into the infarcted hearts of MIRI mouse models, the P-DNAH-I hydrogel effectively inhibited the inflammatory response and reduced the infarct size. In conclusion, our results suggest that the P-DNAH hydrogel, possessing suitable mechanical properties and electroconductivity, serves as an ideal IECH for DDS, delivering irbesartan to promote heart repair.

Fluorinated GlycoNucleoLipid-based hydrogels as new spatiotemporal stimulable DDS.

Achieving a controlled release of several active pharmaceutical ingredients (APIs) remains a challenge for improving their therapeutic effects and reduced their side effects. In the current work, stimulable Drug Delivery Systems (DDS) based on supramolecular hydrogels were designed by combining two APIs featuring anticancer activities, namely the doxorubicin and phenazine 14. In vitro studies revealed promising physicochemical properties for all the investigated API loaded gels. Fluorinated GlycoNucleoLipid (GNF) based supramolecular gels remain stable in the presence of either doxorubicin (Doxo) or phenazine 14 (Phe) as anticancer drugs. Noteworthy, the stiffness of the GNF-based supramolecular gels was enhanced in the presence of both APIs while maintaining their thixotropic properties. We demonstrated that the storage modulus (G') of the GNF gels was increased from 1.3 kPa to 9.3 kPa upon loading of both APIs within the same gels. With a low mechanical stimulation (within the LVR), a passive diffusion out of gels was observed for Dox whereas Phe remained trapped in the GNF gels over several hours. Also, in this work we showed that mechanical stress triggered the release of both Phe and Doxo at different rates.