A novel therapeutic outlook: Classification, applications and challenges of inhalable micron/nanoparticle drug delivery systems in lung cancer (Review).

Lung cancer represents a marked global public health concern. Despite existing treatment modalities, the average 5­year survival rate for patients with patients with lung cancer is only ~20%. As there are numerous adverse effects of systemic administration routes, there is an urgent need to develop a novel therapeutic strategy tailored specifically for patients with lung cancer. Non­invasive aerosol inhalation, as a route of drug administration, holds unique advantages in the context of respiratory diseases. Nanoscale materials have extensive applications in the field of biomedical research in recent years. The present study provides a comprehensive review of the classification, applications summarized according to existing clinical treatment modalities for lung cancer and challenges associated with inhalable micron/nanoparticle drug delivery systems (DDSs) in lung cancer. Achieving localized treatment of lung cancer preclinical models through inhalation is deemed feasible. However, further research is required to substantiate the efficacy and long­term safety of inhalable micron/nanoparticle DDSs in the clinical management of lung cancer.

Salivary Amylase-Responsive Buccal Tablets Wipe Out Chemotherapy-Rooted Refractory Oral Mucositis.

Oral mucositis (OM) is the most common and refractory complication of cancer chemotherapy and radiotherapy, severely affecting patients' life quality, lowering treatment tolerance, and discouraging patient compliance. Current OM delivery systems mostly affect the comfort of patient use and lead to poor compliance and unsatisfactory effects. Herein, salivary amylases (SAs)-responsive buccal tablets consisting of porous manganese-substituted Prussian blue (PMPB) nanocubes (NCs), anti-inflammatory apremilast (Apr) and starch controller have been engineered. PMPB NCs with large surface area can serve as carriers to load Apr, and their multienzyme-mimicking activity enables them to scavenge reactive oxygen species (ROS), which thus synergize with Apr to mitigate inflammation. More significantly, the starch controller can respond to abundant SAs in the oral cavity and realize the cascade, continuous, and complete drug release after enzymatic decomposition, which not only aids with high tissue affinity to prolong the resistance time but also improves the comfort of use. The preclinical study reveals that contributed by the above actions, such buccal tablets mitigate inflammation, promote endothelium proliferation and migration, and accelerate wound healing for repressing chemotherapy-originated intractable OM with positive oral microenvironment and shorter recovery time, thus holding high potentials in clinical translation.

Dielectric Properties of Benzocyclobutene-Based Resin: A Molecular Dynamics Study.

Benzocyclobutene (BCB)-based resins have garnered considerable attention because of their remarkable dielectric properties and thermal stability. However, in molecular dynamics (MD) simulations, progress in BCB-based resin research has yet to keep pace with experimental advancements, resulting in a shortage of theoretical underpinnings at the molecular level. This study focuses on a novel homopolymer, poly(2-(4-benzocyclobutenyl)-divinylbenzene(DVB-S-BCB)), and devises an interactive methodology suitable for BCB-based resins. We implemented a Python script for the joint relaxation method to construct a three-dimensional model of the cured polymer using MadeA and LAMMPS. We conducted MD simulations to investigate how the cross-linking degree and resin molecular weight influence the dielectric properties of the cured polymer. Furthermore, we analyzed the thermodynamic properties through simulation. The results illustrate that augmenting the cross-linking degree and resin molecular weight results in a higher cross-linking density and reduced free volume, thereby increasing the dielectric constant of the resin. The cross-link density does not increase indefinitely with molecular weight, and after a certain threshold is reached, it cannot have a significant effect on the dielectric constant. The degree of cross-linking exerts a more pronounced impact on the dielectric constant than the molecular weight of the resin. In addition, the simulation results denote the excellent thermodynamic properties of the cured polymer. This study also examines the dielectric and thermodynamic properties of the resin samples that were experimentally prepared. The obtained data successfully confirm the reliability of the simulation results. This study offers novel insights for future simulation research on benzocyclobutene-based resins. Additionally, it provides theoretical support for exploring experimental work on low-dielectric materials in the electronic field.

Sequential Ubiquitination and Phosphorylation Epigenetics Reshaping by MG132-Loaded Fe-MOF Disarms Treatment Resistance to Repulse Metastatic Colorectal Cancer.

Abnormal epigenetic regulation is identified to correlate with cancer progression and renders tumor refractory and resistant to reactive oxygen species (ROS)-based anti-tumor actions. To address it, a sequential ubiquitination and phosphorylation epigenetics modulation strategy is developed and exemplified by the well-established Fe-metal-organic framework (Fe-MOF)-based chemodynamic therapy (CDT) nanoplatforms that load the 26S proteasome inhibitor (i.e., MG132). The encapsulated MG132 can blockade 26S proteasome, terminate ubiquitination, and further inhibit transcription factor phosphorylation (e.g., NF-κB p65), which can boost pro-apoptotic or misfolded protein accumulations, disrupt tumor homeostasis, and down-regulate driving genes expression of metastatic colorectal cancer (mCRC). Contributed by them, Fe-MOF-unlocked CDT is magnified to considerably elevate ROS content for repulsing mCRC, especially after combining with macrophage membrane coating-enabled tropism accumulation. Systematic experiments reveal the mechanism and signaling pathway of such a sequential ubiquitination and phosphorylation epigenetics modulation and explain how it could blockade ubiquitination and phosphorylation to liberate the therapy resistance to ROS and activate NF-κB-related acute immune responses. This unprecedented sequential epigenetics modulation lays a solid foundation to magnify oxidative stress and can serve as a general method to enhance other ROS-based anti-tumor methods.

Phosphorus-Containing Flame-Retardant Benzocyclobutylene Composites with High Thermal Stability and Low CTE.

As a component of printed circuit substrate, copper clad laminate (CCL) needs to meet the performance requirements of heat resistance, flame retardancy, and low coefficient of thermal expansion (CTE), which, respectively, affects the stability, safety, and processability of terminal electronic products. In this paper, benzocyclobutylene (BCB)-functionalized phosphorus-oxygen flame retardant composites were prepared through introducing the BCB groups, and the performance was researched by thermogravimetric analysis, microcombustion calorimetry, and thermomechanical analysis. The research results show that these phosphorus oxide compounds containing BCB groups show good thermal stability and low total heat release (THR) after thermal curing, and the more BCB groups on the phosphorus oxide monomers, the better the thermal stability and flame retardancy of cured resins. The Td5 and THR of the composite (M3) are as high as 443 °C and 23.1 kJ/g, respectively. In addition, the CTE of M3 is as low as 16.71 ppm/°C. Introduction of BCB groups which can be crosslinked through heat to improve the thermal stability, flame retardancy, and reduced CTE of traditional organophosphorus flame retardant materials. These materials are expected to be good candidates for CCL substrates for electronic circuits.

Recent Advances in Transition-Metal Based Nanomaterials for Noninvasive Oncology Thermal Ablation and Imaging Diagnosis.

With the developments of nanobiotechnology and nanomedicine, non-invasive thermal ablation with fewer side effects than traditional tumor treatment methods has received extensive attention in tumor treatment. Non-invasive thermal ablation has the advantages of non-invasiveness and fewer side effects compared with traditional treatment methods. However, the clinical efficiency and biological safety are low, which limits their clinical application. Transition-metal based nanomaterials as contrast agents have aroused increasing interest due to its unique optical properties, low toxicity, and high potentials in tumor diagnosis. Transition-metal based nanomaterials have high conversion efficiency of converting light energy into heat energy, good near-infrared absorption characteristics, which also can targetedly deliver those loaded drugs to tumor tissue, thereby improving the therapeutic effect and reducing the damage to the surrounding normal tissues and organs. This article mainly reviews the synthesis of transition-metal based nanomaterials in recent years, and discussed their applications in tumor thermal ablation and diagnosis, hopefully guiding the development of new transition metal-based nanomaterials in enhancing thermal ablation.

High performance low dielectric polybenzocyclobutene nanocomposites with organic-inorganic hybrid silicon nanoparticles.

In this study, benzocyclobutene-functionalized organic-inorganic hybrid spherical silicon nanoparticles (BCBNPs) with controllable size (200-600 nm) and good dispersion were synthesized by a one-step sol-gel method in aqueous solution. The effect of the reaction conditions (time, precursor concentration, pH value and temperature) on the particle size of the BCBNPs and the formation mechanism of the BCBNPs were studied. What is more, homogeneously dispersed BCBNPs/divinyltetramethyldisiloxane-bis(benzocyclobutene) (BCBNPs/PDVSBCB) nanocomposites were prepared and the influence of the incorporation of BCBNPs on the properties of the nanocomposites was investigated. The dielectric constants of the BCBNPs/PDVSBCB nanocomposites were drastically reduced relative to neat PDVSBCB, and were as low as 2.25 (30 MHz). Besides, the thermal and mechanical properties of the BCBNPs/PDVSBCB nanocomposites were significantly improved, evidencing their potential applications in the field of high-performance dielectric materials.

Low dielectric resins derived from hyperbranched carbosilane oligmers functionalized by benzocyclobutene groups.

Polycarbosilanes have been considered as potential materials used in electronic packaging and circuit boards owing to their excellent low-dielectric performance. In this work, we prepared new hyperbranched carbosilane oligomers (HCBOs) which were functionalized by benzocyclobutene (BCB) groups. HCBOs can be thermally cured to produce transparent (HCBRs) with low dielectric constant and high thermostability.

Flexible and low-k polymer featuring hard-soft-hybrid strategy.

One of the main challenges for dielectric materials for advanced microelectronics is their high dielectric value and brittleness. In this study, we adopted a hard-soft-hybrid strategy and successfully introduced a hard, soft segment and covalent crosslinked structural unit into a hybridized skeleton via copolymerization of polydimethylsiloxane (PDMS), benzocyclobutene (BCB) and double-decker-shaped polyhedral silsesquioxanes (DDSQ) by a platinum-catalyzed hydrosilylation reaction, thus producing a random copolymer (PDBD) with a hybridized skeleton in the main chain. PDBD exhibited high molecular weight and thermal curing action without any catalyst. More importantly, the cured copolymer displayed high flexibility, high thermal stability and low dielectric constant, evidencing its potential applications in high-performance dielectric materials.

Apatinib inhibits VEGFR-2 and angiogenesis in an in vivo murine model of nasopharyngeal carcinoma.

Angiogenesis is initiated by the activation of the vascular epidermal growth factor receptor-2 (VEGFR-2) by the vascular epidermal growth factor (VEGF) ligand. Overexpression of VEGFR-2 increases the growth of nasopharyngeal carcinomas (NPC). Apatinib (YN968D1) is a highly-selective inhibitor of VEGFR-2, but its effects on NPC have not been hitherto investigated. In the present study, CNE-2 NPC cells were xenografted into 132 nude mice, which were treated with one of 6 drug regimens of apatinib administered alone or in combination with cisplatin (DDP). The impact of treatment regimens on the growth, microvascularization, apoptosis, and metabolic response of tumors, as well as mouse survival was determined by histopathology, immunohistochemistry (VEGFR-2 and CD31), terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL), micro 18F-FDG PET/CT imaging and survival curves. Administration of apatinib alone inhibited tumor growth, reduced microvascular density, and facilitated the apoptosis of tumors. Tumors treated simultaneously with apatinib and cisplatin exhibited significantly-increased inhibition of tumor growth, prolonged survival time, decreased expression of VEGFR-2, reduced microvascular density, and frequency of apoptosis over standalone and sequential administration therapy. Tumors treated simultaneously with apatinib and cisplatin had the lowest uptake of FDG. Taken together, the simultaneous administration of apatinib and cisplatin improves the therapeutic efficacy over standalone treatments, which also led to improved efficacy over sequential administration regimens. VEGFR-2 is an important predictive marker for efficacy of apatinib treatment of NPC.

Novel composite drug delivery system as a novel radio sensitizer for the local treatment of cervical carcinoma.

In this study, we investigated in vivo radiosensitizing effects of a gel-based dual drug delivery system (DDS) (PECE/DDP + mPEG-PCL/PTX, or PDMP) in a cervical cancer model, and determined its possible mechanisms of action. A xenograft cervical cancer model was used to investigate the radio sensitization effect of PDMP. Mice underwent paclitaxel (PTX) + cisplatin (DDP), PECE, or PDMP treatment followed by single radiation doses ranging from 0 Gy to 20 Gy. Radio sensitization was analyzed by tumor regrowth delay (TGD). The sensitization enhancement ratio (SER) was calculated by the doses needed to yield TGD when using radiation treatment alone and when using radiation plus drug treatment. The impact of irradiation and drugs on TGD was determined, and an optimum radiation dose was chosen for further evaluation of radio sensitizing effects. The data showed that PDMP yielded the highest radio sensitization (SER was 1.3) and a radiation dose of 12 Gy was chosen for further investigation. PDMP + radiotherapy treatment was most effective in inhibiting tumor growth, prolonging survival time, decreasing expression of CD31, CD133, and aldehyde dehydrogenase 1 (ALDH1), inducing G2/M phase arrest, apoptosis, and expression of Ataxia telangiectasia mutated (ATM) and histone H2AX phosphorylation (γ-H2AX). Thus, our data indicated that PDMP is a promising anti-tumor and radio sensitization reagent for the treatment of cervical carcinoma.

Paclitaxel-loaded polymeric nanoparticles combined with chronomodulated chemotherapy on lung cancer: In vitro and in vivo evaluation.

The objective of our study was to examine the anti-tumor effect of paclitaxel (PTX)-loaded polymeric nanoparticles (PTX-NPs) combined with circadian chronomodulated chemotherapy. Our intention was to screen out the best time of the day for the drug to be administered. PTX-NPs with a diameter of approximately 168nm were prepared through a thin film dispersion technique. The PTX in PTX-NPs showed an initial fast release subsequently a slower and sustained release. The cytotoxicity of chronomodulated administration of PTX-NPs in vitro confirmed that its cytotoxic effect was lower than that of PTX injection, and showed a time-dependent effect. In addition, anti-tumor effect was examined by analysing tumor growth inhibition rate, micro-vessel density (MVD), cell proliferation and cell apoptosis, following either injection with PTX or administration of PTX-NPs. Micro fluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) was used to evaluate tumor reactivity to PTX-NPs combined with chronomodulated chemotherapy. Taken these results into consideraion, our experiment indicates that PTX-NPs exhibit greater anti-tumor activity against A549 cells, in comparison with PTX injection, and the anti-tumor effect at 15h after light onset (HALO) administration is the best in all groups. Therefore, prepared PTX-NPs combined with chronomodulated chemotherapy could be a potential treatment for lung cancer.