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International Journal of Molecular... Aug 2024Osteosarcoma (OS) is a highly malignant primary bone neoplasm that is the leading cause of cancer‑associated death in young people. GNE‑477 belongs to the second...
Osteosarcoma (OS) is a highly malignant primary bone neoplasm that is the leading cause of cancer‑associated death in young people. GNE‑477 belongs to the second generation of mTOR inhibitors and possesses promising potential in the treatment of OS but dose tolerance and drug toxicity limit its development and utilization. The present study aimed to prepare a novel HO stimulus‑responsive dodecanoic acid (DA)‑phenylborate ester‑dextran (DA‑B‑DEX) polymeric micelle delivery system for GNE‑477 and evaluate its efficacy. The polymer micelles were characterized by morphology, size and critical micelle concentration. The GNE‑477 loaded DA‑B‑DEX (GNE‑477@DBD) tumor‑targeting drug delivery system was established and the release of GNE‑477 was measured. The cellular uptake of GNE‑477@DBD by three OS cell lines (MG‑63, U2OS and 143B cells) was analyzed utilizing a fluorescent tracer technique. The hydroxylated DA‑B was successfully grafted onto dextran at a grafting rate of 3%, suitable for forming amphiphilic micelles. Following exposure to HO, the DA‑B‑DEX micelles ruptured and released the drug rapidly, leading to increased uptake of GNE‑477@DBD by cells with sustained release of GNE‑477. The experiments, including MTT assay, flow cytometry, western blotting and RT‑qPCR, demonstrated that GNE‑477@DBD inhibited tumor cell viability, arrested cell cycle in G1 phase, induced apoptosis and blocked the PI3K/Akt/mTOR cascade response. , through the observation of mice tumor growth and the results of H&E staining, the GNE‑477@DBD group exhibited more positive therapeutic outcomes than the free drug group with almost no adverse effects on other organs. In conclusion, HO‑responsive DA‑B‑DEX presents a promising delivery system for hydrophobic anti‑tumor drugs for OS therapy.
Topics: Animals; Humans; Micelles; Osteosarcoma; Hydrogen Peroxide; Cell Line, Tumor; Dextrans; Mice; Lauric Acids; Apoptosis; Polymers; Xenograft Model Antitumor Assays; Bone Neoplasms; Mice, Nude; Antineoplastic Agents; Mice, Inbred BALB C; Male; TOR Serine-Threonine Kinases
PubMed: 38940336
DOI: 10.3892/ijmm.2024.5393 -
Advances in Pharmacological and... 2024Sonophoresis is the most approachable mode of transdermal drug delivery system, wherein low-frequency sonophoresis penetrates the drug molecules into the skin. It is an... (Review)
Review
Sonophoresis is the most approachable mode of transdermal drug delivery system, wherein low-frequency sonophoresis penetrates the drug molecules into the skin. It is an alternative method for an oral system of drug delivery and hypodermal injections. The cavitation effect is thought to be the main mechanism used in sonophoresis. The cavitation process involves forming a gaseous bubble and its rupture, induced in the coupled medium. Other mechanisms used are thermal effects, convectional effects, and mechanical effects. It mainly applies to transporting hydrophilic drugs, macromolecules, gene delivery, and vaccine delivery. It is also used in carrier-mediated delivery in the form of micelles, liposomes, and dendrimers. Some synergistic effects of sonophoresis, along with some permeation enhancers, such as chemical enhancers, iontophoresis, electroporation, and microneedles, increased the effectiveness of drug penetration. Sonophoresis-mediated ocular drug delivery, nail drug delivery, gene delivery to the brain, sports medicine, and sonothrombolysis are also widely used. In conclusion, while sonophoresis offers promising applications in diverse fields, further research is essential to comprehensively elucidate the biophysical mechanisms governing ultrasound-tissue interactions. Addressing these gaps in understanding will enable the refinement and optimization of sonophoresis-based therapeutic strategies for enhanced clinical efficacy.
PubMed: 38938593
DOI: 10.1155/2024/1247450 -
Chemosphere Jun 2024PER: and polyfluorinated alkyl substances, especially perfluorooctanoic acid and perfluorooctane sulfonic acid (PFOX), have attracted considerable attention lately... (Review)
Review
PER: and polyfluorinated alkyl substances, especially perfluorooctanoic acid and perfluorooctane sulfonic acid (PFOX), have attracted considerable attention lately because of their widespread occurrence in aquatic environment and potential biological toxicity to animals and human beings. The development of economical, efficient, and engineerable adsorbents for removing PFOX in water has become one of the research focuses. This review summarized the recent progress on natural mineral and industrial solid based adsorbent (NM&ISW-A) and removal mechanisms concerning PFOX onto NM&ISW-A, as well as proposed the current challenges and future perspectives of using NM&ISW-A for PFOX removal in water. Kaolinite and montmorillonite are usually used as model clay minerals for PFOX removal, and have been proved to adsorb PFOX by ligand exchange and electrostatic attraction. Fe-based minerals, such as goethite, magnetite, and hematite, have better PFOX adsorption capacity than clay minerals. The adsorbent prepared from industrial solid waste by high temperature roasting has great potential application prospects. Fabricating nanomaterials, amination modification, surfactant modification, fluorination modification, developing versatile composites, and designing special porous structure are beneficial to improve the adsorption performance of PFOX onto NM&ISW-A by enhancing the specific surface area, positive charge, and hydrophobicity. Electrostatic interaction, hydrophobic interaction, hydrogen bond, ligand and ion exchange, and self-aggregation (formation of micelle or hemimicelle) are the main adsorption mechanisms of PFOX by NM&ISW-A. Among them, electrostatic and hydrophobic interactions play a considerable role in the removal of PFOX by NM&ISW-A. Therefore, NM&ISW-A with electrostatic functionalities and considerable hydrophobic segments enables rapid, efficient, and high-capacity removal of PFOX. The future directions of NM&ISW-A for PFOX removal include the preparation and regeneration of engineerable NM&ISW-A, the development of coupling technology for PFOX removal based on NM&ISW-A, the in-depth research on adsorption mechanism of PFOX by NM&ISW-A, as well as the development of NM&ISW-A for PFOX alternatives removal. This review paper would be helpful the comprehensive understanding of NM&ISW-A potential for PFOX removal and the PFOX removal mechanisms, and identifies the gaps for future research and development.
PubMed: 38936483
DOI: 10.1016/j.chemosphere.2024.142662 -
ACS Nano Jun 2024Constructing carbonaceous materials with versatile surface structures still remains a great challenge due to limited self-assembly methods, especially at high...
Constructing carbonaceous materials with versatile surface structures still remains a great challenge due to limited self-assembly methods, especially at high temperatures. This study presents an innovative template evolution induced relay self-assembly (TEIRSA) for the fabrication of large polyoxometalate (POM)-mixed carbonaceous nanosheets featuring surface mesoporous structures through hydrothermal carbonization (HTC). The method employs POM and acetone as additives, cleverly modulating the Ostwald ripening-like process of P123-based micelles, effectively addressing the instability challenges inherent in traditional soft-template methods, especially within the demanding carbohydrate HTC process. Additionally, this method allows for the independent regulation of surface architectures through the selection of organic additives. The resulting nanosheets exhibit diverse surface morphologies, including surface spherical mesopores, 1D open channels, and smooth surfaces. Their unexpectedly versatile properties have swiftly garnered recognition, showing potential in the application of lithium-sulfur batteries.
PubMed: 38935973
DOI: 10.1021/acsnano.4c03744 -
The Journal of Physical Chemistry. B Jun 2024Ether-linked surfactants are widely used in formulations such as liquid soaps, but despite their ubiquity, it is unclear how -ethylene glycol linkers in surfactants,...
Ether-linked surfactants are widely used in formulations such as liquid soaps, but despite their ubiquity, it is unclear how -ethylene glycol linkers in surfactants, such as sodium lauryl -(ethylene glycol) sulfate (SLEnS), influence micellar packing in the presence of NaCl. In the present work, we probe the structure and hydration of ether linkers in micelles comprising monodisperse SLEnS surfactants using contrast-variation small-angle neutron scattering (CV-SANS) and small-angle X-ray scattering (SAXS). Using SAXS, changes in micellar structure were observed for SLEnS ( = 1, 2, or 3) arising from the extent of ethoxylation. Scattering profiles indicated a clear transition from elongated cylindrical micelles to shorter ellipsoidal micelles with increasing ethoxylation. With CV-SANS, micellar structure and linker geometries of SLE3S were able to be resolved, indicating that a change in micellar architecture is modulated by dehydration of the tri(ethylene glycol) linker, offering new insights into the role of water and ions in the self-assembly of this key class of surfactants.
PubMed: 38935971
DOI: 10.1021/acs.jpcb.4c03429 -
Environmental Science & Technology Jun 2024Understanding the bioavailability of per- and polyfluoroalkyl substances (PFAS) in food is essential for accurate human health risk assessment. Given the rising...
Understanding the bioavailability of per- and polyfluoroalkyl substances (PFAS) in food is essential for accurate human health risk assessment. Given the rising incidence of inflammatory bowel disease (IBD), this study aimed to investigate the impacts of IBD on the bioavailability of PFAS in food using mice models. The relative bioavailability (RBA) of PFAS was the highest in the chronic IBD mice (64.3-144%), followed by the healthy (60.8-133%) and acute IBD mice (41.5-121%), suggesting that chronic IBD enhanced the PFAS exposure risk. tests showed that the intestinal micelle stability increased as a result of reduced content of short-chain fatty acids, thus promoting the PFAS bioaccessibility in the digestive fluid of chronic IBD. Additionally, increased pathogenic and decreased beneficial bacteria in the gut of IBD groups facilitated the intestinal permeability, thus enhancing PFAS absorption. These together explained the higher RBA of PFAS in the chronic IBD. However, remarkably lower enzymatic activities suggested severely impaired digestive ability in the acute IBD, which facilitated the excretion of PFAS from feces, thus lowering the RBA. Conversely, PFAS exposure might exacerbate IBD by changing the gut microbiota structures. This study hints that individuals with chronic intestinal inflammation might have higher PFAS exposure risk than the healthy population.
PubMed: 38934536
DOI: 10.1021/acs.est.4c01511 -
ACS Applied Materials & Interfaces Jun 2024Polyplexes are required to be equipped with multiple functionalities to accomplish adequate structure stability and gene transfection efficacy for gene therapy. Herein,...
Polyplexes are required to be equipped with multiple functionalities to accomplish adequate structure stability and gene transfection efficacy for gene therapy. Herein, a 4-carboxy-3-fluorophenylboronic acid (FPBA)-functionalized block copolymer of PEG--PAsp(DET/FBA) and PAsp(DET/FBA) (abbreviated as PB and HB) was synthesized and applied for engineering functional polyplex micelles (PMs) through ionic complexation with pDNA followed by strategic cross-linking with nordihydroguaiaretic acid (NDGA) in respect to the potential linkage of polyphenol and FPBA moieties. In relation to polyplex micelles void of cross-linking, the engineered multifunctional polyplex micelles (PBHBN-PMs) were determined to possess improved structural tolerability against the exchange reaction with charged species. Besides, the FPBA/NDGA cross-linking appeared to be selectively cleaved in the acidic endosomal compartments but not the neutral milieu. Furthermore, the PBHB-PMs with the optimal FPBA/NDGA cross-linking degree were identified to possess appreciable cellular uptake and endosomal escape activities, eliciting a significantly high level of gene expression relative to P-PMs and PB-PMs. Eventually, antitumor therapy by our proposed multifunctional PMs appeared to be capable of facilitating expression of the antiangiogenic genomic payloads (sFlt-1 pDNA) via systemic administration. The enriched antiangiogenic sFlt-1 in the tumors could silence the activities of angiogenic cytokines for the inhibited neo-vasculature and the suppressed growth of orthotopic 4T1 tumors. Of note, the persistent expression of the antiangiogenic sFlt-1 is also presumed to migrate into the blood circulation, thereby accounting for an overall antiangiogenic environment in preventing the potential pulmonary metastasis. Hence, our elaborated multifaceted PMs inspired fascinating potential as an intriguing gene delivery system for the treatment of clinical solid tumors and metastasis.
PubMed: 38934519
DOI: 10.1021/acsami.4c05311 -
Small (Weinheim An Der Bergstrasse,... Jun 2024Acute myeloid leukemia (AML) is a common and catastrophic hematological neoplasm with high mortality rates. Conventional therapies, including chemotherapy, hematopoietic... (Review)
Review
Acute myeloid leukemia (AML) is a common and catastrophic hematological neoplasm with high mortality rates. Conventional therapies, including chemotherapy, hematopoietic stem cell transplantation (HSCT), immune therapy, and targeted agents, have unsatisfactory outcomes for AML patients due to drug toxicity, off-target effects, drug resistance, drug side effects, and AML relapse and refractoriness. These intrinsic limitations of current treatments have promoted the development and application of nanomedicine for more effective and safer leukemia therapy. In this review, the classification of nanoparticles applied in AML therapy, including liposomes, polymersomes, micelles, dendrimers, and inorganic nanoparticles, is reviewed. In addition, various strategies for enhancing therapeutic targetability in nanomedicine, including the use of conjugating ligands, biomimetic-nanotechnology, and bone marrow targeting, which indicates the potential to reverse drug resistance, are discussed. The application of nanomedicine for assisting immunotherapy is also involved. Finally, the advantages and possible challenges of nanomedicine for the transition from the preclinical phase to the clinical phase are discussed.
PubMed: 38934349
DOI: 10.1002/smll.202403409 -
Biomaterials Research 2024Malignant cancers, known for their pronounced heterogeneity, pose substantial challenges to monotherapeutic strategies and contribute to the risk of metastasis....
Malignant cancers, known for their pronounced heterogeneity, pose substantial challenges to monotherapeutic strategies and contribute to the risk of metastasis. Addressing this, our study explores the synergistic potential of combining boron neutron capture therapy (BNCT) with immune checkpoint blockade to enhance cancer treatment efficacy. We synthesized boron-rich block copolymer micelles as a novel boron drug for BNCT. Characterization was conducted using nuclear magnetic resonance, gel-permeation chromatography, transmission electron microscopy, and dynamic light scattering. These micelles, with an optimal size of 91.3 nm and a polydispersity index of 0.18, are suitable for drug delivery applications. In vitro assessments on B16-F10 melanoma cells showed a 13-fold increase in boron uptake with the micelles compared to borophenyl alanine (BPA), the conventional boron drug for BNCT. This resulted in a substantial increase in BNCT efficacy, reducing cell viability to 77% post-irradiation in micelle-treated cells, in contrast to 90% in BPA-treated cells. In vivo, melanoma-bearing mice treated with these micelles exhibited an 8-fold increase in boron accumulation in tumor tissues versus those treated with BPA, leading to prolonged tumor growth delay (5.4 days with micelles versus 3.3 days with BPA). Moreover, combining BNCT with anti-PD-L1 immunotherapy further extended the tumor growth delay to 6.6 days, and enhanced T-cell infiltration and activation at tumor sites, thereby indicating a boosted immune response. This combination demonstrates a promising approach by enhancing cytotoxic T-cell priming and mitigating the immunosuppressive effects of melanoma tumors.
PubMed: 38933089
DOI: 10.34133/bmr.0040 -
Pharmaceutics May 2024The current research aims to develop thermosensitive polymeric micelles loaded with risperidone for nasal administration, emphasizing the added benefits of their...
The current research aims to develop thermosensitive polymeric micelles loaded with risperidone for nasal administration, emphasizing the added benefits of their thermosensitive behavior under nasal conditions. An initial risk assessment facilitated the advanced development process, confirming that the key indicators of thermosensitivity were suitable for nasal application. The polymeric micelles exhibited an average size of 118.4 ± 3.1 nm at ambient temperature and a size of 20.47 ± 1.2 nm at 36.5 °C, in both cases in monodisperse distribution. Factors such as pH and viscosity did not significantly impact these parameters, demonstrating appropriate nasal applicability. The model formulations showed a rapid, burst-like drug release profile in vitro, accompanied by a quick and high permeation rate at nasal conditions. Overall, the Quality by Design-based risk assessment process led to the development of an advanced drug delivery system capable of administering risperidone through the nasal cavity.
PubMed: 38931827
DOI: 10.3390/pharmaceutics16060703