RSC Pharmaceutics最新文献

筛选
英文 中文
Potential to modulate corneal epithelial repair via nitric oxide-releasing glycosaminoglycans. 通过释放一氧化氮的糖胺聚糖调节角膜上皮修复的潜力。
IF 5.5
RSC Pharmaceutics Pub Date : 2026-10-09 DOI: 10.1039/d6pm00190d
Margery E Purvis, Madelyn P Bucci, Tsian D Ramrattan, Shannon M Wallet, Mark H Schoenfisch
{"title":"Potential to modulate corneal epithelial repair <i>via</i> nitric oxide-releasing glycosaminoglycans.","authors":"Margery E Purvis, Madelyn P Bucci, Tsian D Ramrattan, Shannon M Wallet, Mark H Schoenfisch","doi":"10.1039/d6pm00190d","DOIUrl":"https://doi.org/10.1039/d6pm00190d","url":null,"abstract":"<p><p>Bioactive wound therapies that protect injured tissue, promote regeneration, and prevent infection would represent a promising alternative to traditional passive treatments. In this study, nitric oxide (NO)-releasing glycosaminoglycans (GAGs) were synthesized and evaluated for their therapeutic potential in corneal wound healing. Low and high molecular weight hyaluronic acid (HA) and chondroitin sulfate (CS) derivatives of different sulfation patterns were synthesized and characterized with respect to NO release, antibacterial activity, cytotoxicity, and effects on human corneal epithelial cell proliferation and migration. A three-dimensional corneal tissue scratch closure model was subsequently used to assess <i>in vitro</i> barrier restoration. A derivative consisting of CS with prolonged NO release and low molecular weight HA with intermediate NO-release kinetics were identified as the most promising materials. The HA derivative enhanced epithelial migration even during later timepoints of the migration assays. A carboxymethylcellulose (CMC) gel formulation containing the HA derivative further promoted cell migration. In corneal tissue models, treatment with both the free and CMC-formulated NO-releasing HA enhanced restoration. Barrier recovery, as measured by transepithelial electrical resistance, confirmed restoration of tissue integrity post-wounding, concomitant with a cytokine milieu associated with pro-wound healing. Overall, NO-releasing, low molecular weight HA in a CMC gel formulation represents a promising bioactive strategy for promoting corneal wound repair.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hyaluronic acid-b-polylactic acid polymersomes facilitate CD44-mediated delivery of doxorubicin to glioblastoma in vitro. 透明质酸-b聚乳酸聚合体促进cd44介导的阿霉素向胶质母细胞瘤的体外递送。
IF 5.5
RSC Pharmaceutics Pub Date : 2026-09-15 DOI: 10.1039/d6pm00188b
Apoorvi Chaudhri, Molli Garifo, Pranavi Thatavarthi, Torrick Fletcher, Jessica Larsen
{"title":"Hyaluronic acid-<i>b</i>-polylactic acid polymersomes facilitate CD44-mediated delivery of doxorubicin to glioblastoma <i>in vitro</i>.","authors":"Apoorvi Chaudhri, Molli Garifo, Pranavi Thatavarthi, Torrick Fletcher, Jessica Larsen","doi":"10.1039/d6pm00188b","DOIUrl":"10.1039/d6pm00188b","url":null,"abstract":"<p><p>Glioblastoma represents a highly aggressive brain tumor with low survival and no response to chemotherapy and radiation therapy. Temozolomide, the current standard of care chemotherapy, improves patient survival by only about 6 months because of several resistance mechanisms, including unmethylated MGMT, which enables repair of chemotherapy-induced DNA damage. Thus, additional treatment strategies are necessary to investigate efficient responses towards glioblastoma. Doxorubicin (DOX) is a chemotherapeutic agent that is independent of MGMT methylation and instead works through inhibition of topoisomerase (TOPO) II, an enzyme necessary for DNA replication of the tumor. The inability of doxorubicin to cross the blood-brain barrier (BBB) precludes its use in glioblastoma. Polymersome nanoparticles have the potential to transport agents across the BBB. Here, we develop hyaluronic acid-<i>b</i>-polylactic acid (HA-PLA) polymeric nanoparticles called polymersomes, encapsulate them with DOX and investigate the ability of our system to induce apoptosis in a human glioblastoma cell line. HA-PLA polymersomes encapsulated with DOX at 6 µg mL<sup>-1</sup> showed an encapsulation efficiency of 99 ± 1% and a PDI of 0.70 ± 0.02 with diameter of 122.1 ± 2.9 nm, with encapsulation efficiency decreasing and diameter increasing as additional DOX is added. Release studies showed an increase in DOX released from HA-PLA-based polymersomes due to acid-mediated hydrolysis of the PLA ester bonds. The HA-PLA polymersomes show specificity and receptor-mediated endocytosis towards CD44-positive U87 glioblastoma cells with ∼42% uptake due to the natural affinity of HA (hyaluronic acid) to CD44. This receptor-mediated and additional mode of endocytosis was greatly stunted at 4 °C. Jurkat cells that are CD44 negative did not show uptake. Our HLA-PLA-DOX system promotes apoptosis of glioblastoma through inhibition of topoisomerase (TOPO) II. Thus, our system could allow tumor specificity through HA-CD44 affinity and slow drug release through pH sensitivity of PLA in the acidic tumor microenvironment.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nose-to-brain delivery of IRX4204 by cell-adhesion peptide-functionalized gemini surfactant-phospholipid nanoparticles. 细胞粘附肽功能化gemini表面活性剂-磷脂纳米颗粒经鼻至脑递送IRX4204。
IF 5.5
RSC Pharmaceutics Pub Date : 2026-09-09 eCollection Date: 2026-09-22 DOI: 10.1039/d6pm00414h
Antoine Hakim, Gracious D S Kasheke, George S Robertson, Marianna Foldvari
{"title":"Nose-to-brain delivery of IRX4204 by cell-adhesion peptide-functionalized gemini surfactant-phospholipid nanoparticles.","authors":"Antoine Hakim, Gracious D S Kasheke, George S Robertson, Marianna Foldvari","doi":"10.1039/d6pm00414h","DOIUrl":"10.1039/d6pm00414h","url":null,"abstract":"<p><p>Efficient delivery of hydrophobic therapeutics to the central nervous system (CNS) remains challenging due to poor solubility, limited blood-brain barrier permeability and systemic toxicity. Here, we report the development of gemini surfactant-phospholipid nanoparticles (GPNPs) for intranasal delivery of the highly potent and preferential retinoid X receptor agonist IRX4204. Physicochemical characterization demonstrated stable nanoparticles (60 nm, +40 mV) with high encapsulation efficiency and long-term stability. Dynamic light scattering, transmission electron microscopy and small-angle X-ray scattering revealed that optimal drug loading in GPNPs is ≤0.5 mg mL<sup>-1</sup>. The formulations showed the coexistence of two structurally distinct particle populations, flattened micelles and larger vesicular structures. <i>In vivo</i> studies in mice demonstrated that intranasal administration of IRX4204-GPNPs (0.12 mg kg<sup>-1</sup>) achieved higher CNS concentrations than a 100-fold higher oral dose (12 mg kg<sup>-1</sup>), with sustained distribution across various CNS regions and enhanced striatal accumulation. Compared to oral IRX4204 suspension administration, intranasal delivery of IRX4204-GPNPs achieved about 1.4-fold higher CNS drug concentrations, 136-fold greater delivery efficiency (0.19% <i>vs.</i> 0.0014% of dose) and 73.5% direct transport percentage (DTP), accompanied by markedly reduced plasma and liver exposure. Pharmacodynamic evaluation confirmed sustained activation of RXR-responsive genes, including SCD1 and LXRα, following intranasal nanoparticle delivery. These findings demonstrate that optimized GPNPs enable efficient CNS targeting and support their use as a promising intranasal platform for delivery of RXR agonists and other hydrophobic therapeutics.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":"1442-1454"},"PeriodicalIF":5.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phosphatidylserine-based liposomes encapsulating DMX-5804 protect against doxorubicin-induced cardiotoxicity. 磷脂酰丝氨酸脂质体包封DMX-5804保护防止阿霉素诱导的心脏毒性。
IF 5.5
RSC Pharmaceutics Pub Date : 2026-08-18 DOI: 10.1039/d6pm00059b
Jessica Tetterton-Kellner, Audreanna Miserendino, Imran Tariq, Brian C Jensen, Juliane Nguyen
{"title":"Phosphatidylserine-based liposomes encapsulating DMX-5804 protect against doxorubicin-induced cardiotoxicity.","authors":"Jessica Tetterton-Kellner, Audreanna Miserendino, Imran Tariq, Brian C Jensen, Juliane Nguyen","doi":"10.1039/d6pm00059b","DOIUrl":"10.1039/d6pm00059b","url":null,"abstract":"<p><p>Anthracycline induced cardiotoxicity is a significant problem for oncologists and cancer patients. The leading cause of non-cancer death in cancer patients and survivors is heart failure, which is frequently attributed to the exposure to chemotherapeutics like anthracyclines. The most notorious of these chemotherapeutics is doxorubicin, which causes cardiac contractile dysfunction, which in some cases is irreversible. In this study, we report the development of NanoDMX, a phosphatidylserine-containing liposomal formulation of DMX5804, a small molecule inhibitor of MAP4K4, and demonstrate that its administration prevents doxorubicin-induced left ventricular dysfunction in mice. Additionally, we demonstrate that DMX-5804 protects cardiomyocytes <i>in vitro</i> through a combination of mechanisms outside of the expected route of suppressing the JNK pathway. Overall, we demonstrate that the use of NanoDMX, a novel liposomal system using both DMX-5804 and phosphatidylserine, can prevent the damage induced by doxorubicin over the course of a single high dose <i>in vivo</i> model.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative evaluation of USP II, USP IV, TIM-2, and the dynamic colon model as surrogates for human colonic drug dissolution. USP II、USP IV、TIM-2和动态结肠模型作为人类结肠药物溶出度替代物的比较评价。
IF 5.5
RSC Pharmaceutics Pub Date : 2026-07-22 eCollection Date: 2026-09-22 DOI: 10.1039/d6pm00090h
Khushi Khandelwal, Eleanor Jones, Connor O'Farrell, Hannah Katharine Batchelor
{"title":"Comparative evaluation of USP II, USP IV, TIM-2, and the dynamic colon model as surrogates for human colonic drug dissolution.","authors":"Khushi Khandelwal, Eleanor Jones, Connor O'Farrell, Hannah Katharine Batchelor","doi":"10.1039/d6pm00090h","DOIUrl":"10.1039/d6pm00090h","url":null,"abstract":"<p><p>This study compares conventional dissolution apparatuses (USP II and IV) with advanced biorelevant models (TIM-2 and the Dynamic Colon Model, DCM) for assessing colonic drug dissolution. Theophylline dissolution from modified-release Uniphyllin Continus® tablets was evaluated across varying hydrodynamic conditions, with the DCM serving as a physiologically validated benchmark. Dissolution was highly dependent on USP II paddle speed (50-200 rpm). In the USP IV increasing flow rate (4-50 mL min<sup>-1</sup>) increased 24 h dissolution but had relatively low impact at 1-5 h. In both systems, the lowest agitation conditions (50 rpm and 4 mL min<sup>-1</sup>) provided the closest agreement to DCM profiles. A simplified TIM-2 configuration was used to isolate hydrodynamic effects, demonstrating motility-dependent release, with slower mixing producing dissolution profiles most similar to the DCM. Incorporation of dewatering improved agreement with the stimulated DCM condition for all systems. The consistent trend across systems of improving similarity to the DCM data with decreasing agitation suggests that conditions below the ranges tested here may be warranted in future studies. USP II and USP IV remain practical and robust tools for quality control but TIM-2 and the DCM better replicate colonic hydrodynamics. TIM-2, even in its simplified configuration in this study, offers additional capability to modulate peristaltic motility patterns and provides a promising platform into which the standard TIM colonic fluids, secretion and absorption functions, can be progressively reintroduced to improve biopredictivity. These findings highlight the complementary role of conventional and advanced dissolution approaches and support integrating physiologically relevant parameters into dissolution testing frameworks to improve biopredictive assessment for modified release formulations.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":"3 5","pages":"1353-1363"},"PeriodicalIF":5.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13596085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sequential- vs. density gradient-centrifugation for the isolation of mitochondria-containing extracellular vesicles. 序列与密度梯度离心分离含线粒体的细胞外囊泡。
IF 5.5
RSC Pharmaceutics Pub Date : 2026-07-16 eCollection Date: 2026-09-22 DOI: 10.1039/d5pm00316d
Kandarp M Dave, Bodhi T Brady, Balaji Govindaswamy, Vivek S Basudkar, Donna B Stolz, Devika S Manickam
{"title":"Sequential- <i>vs</i>. density gradient-centrifugation for the isolation of mitochondria-containing extracellular vesicles.","authors":"Kandarp M Dave, Bodhi T Brady, Balaji Govindaswamy, Vivek S Basudkar, Donna B Stolz, Devika S Manickam","doi":"10.1039/d5pm00316d","DOIUrl":"10.1039/d5pm00316d","url":null,"abstract":"<p><p>A subset of extracellular vehicles (EVs) with particle diameters >200 nm, large vesicles (lEVs), contain mitochondria that increase recipient cell bioenergetics. To date, sequential centrifugation (SC) is the most reported protocol to separate lEVs from the smaller EVs (<200 nm)/exosomes. We have previously demonstrated that lEVs derived from brain endothelial cells (BECs) using the standard SC method transfer their innate mitochondria to recipient BECs, increase recipient BEC bioenergetics, reduce brain infarct volume, and improve sensorimotor functions in a mouse model of transient ischemic stroke. Despite their promising therapeutic activity, SC-isolated lEVs are likely a mixture of mitochondria-containing lEVs and non-mitochondria-containing lEVs. We hypothesized that subsequent purification of SC-isolated lEVs using density-gradient centrifugation (DGC) may yield a purer sample of mitochondria-containing lEVs. We established a DGC protocol to purify lEVs. In this pilot study, lEVs isolated using SC and DGC protocols were compared to determine their physicochemical characteristics and their effects on recipient BEC bioenergetics. SC-lEVs and DGC-lEVs both significantly restored ATP levels in OGD-injured BECs with no difference between groups. However, a Seahorse mitochondrial function assay revealed distinct functional effects: SC-lEVs did not significantly alter respiration, whereas DGC-lEVs induced a dose-dependent increase in oxygen consumption rate, indicating enhanced oxidative phosphorylation. These findings demonstrate that DGC purification yields a more mitochondria-enriched and functionally potent lEV preparation with an enhanced capacity to restore oxidative phosphorylation in post-ischemic BECs.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":"1201-1216"},"PeriodicalIF":5.5,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ultrasound-triggered release of an active Wnt signalling agent (6-bromoindirubin-3-oxime) from perfluorocarbon nanodroplets. 超声触发从全氟碳纳米液滴释放活性Wnt信号剂(6-溴靛玉红-3-肟)。
IF 5.5
RSC Pharmaceutics Pub Date : 2026-07-13 eCollection Date: 2026-09-22 DOI: 10.1039/d5pm00186b
Anastasia Polydorou, Qiang Wu, Aya Ben Issa, Jonathan P May, Sara Ferri, Dario Carugo, Eleanor Stride, Nicholas D Evans
{"title":"Ultrasound-triggered release of an active Wnt signalling agent (6-bromoindirubin-3-oxime) from perfluorocarbon nanodroplets.","authors":"Anastasia Polydorou, Qiang Wu, Aya Ben Issa, Jonathan P May, Sara Ferri, Dario Carugo, Eleanor Stride, Nicholas D Evans","doi":"10.1039/d5pm00186b","DOIUrl":"10.1039/d5pm00186b","url":null,"abstract":"<p><p>Ultrasound-activated perfluorocarbon nanodroplets (NDs) have potential as circulating agents for non-invasive, targeted drug delivery. NDs can be induced to cavitate under focussed ultrasound stimulation, releasing a therapeutic payload. They have been explored widely as a means of drug delivery in oncology but there is less information available on their use in regenerative medicine. Here, we tested the hypothesis that NDs could be fabricated to incorporate an agonist of Wnt signalling, a pathway common to many regenerative tissue-specific processes, and to release it in active form upon ultrasound stimulation. NDs were formed by ultrasonic emulsification of perfluorobutane in the presence of 6-bromoindirubin-3-oxime (BIO) and phospholipids: DSPC and DSPE-PEG2000. The nanodroplet formulation (∼200 nm diameter and 5 × 10<sup>9</sup> mL<sup>-1</sup>) was stable in aqueous suspension for up to 10 days at 4 °C, but gradual passive release of BIO was observed over a period of hours (15-30% release in 24 hours) in serum-containing growth medium at 37 °C, as measured by high pressure liquid chromatography. NDs were not toxic to either primary or continuous bone-derived cells and induced signalling in a 3T3 Wnt reporter cell line, indicating that the released BIO was active. Rapid release of BIO was achieved by exposing NDs to ultrasound. 25% BIO release was observed after 30 s of exposure to ultrasound (0.9 MHz centre frequency, 0.75 MPa peak negative pressure, 1 kHz pulse repetition frequency, 10% duty cycle) and activated Wnt signalling in cells. Our data indicate that NDs may be used to incorporate and deliver a Wnt pathway activator in response to ultrasound stimulation and that they have potential as drug delivery agents for regenerative medicine applications.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":"1253-1265"},"PeriodicalIF":5.5,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148898831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Co-formulation of IL-12 mRNA and doxorubicin in polymeric nanoparticles for simultaneous delivery in murine melanoma. IL-12 mRNA和阿霉素在聚合纳米颗粒中的联合配方用于小鼠黑色素瘤的同时递送。
IF 5.5
RSC Pharmaceutics Pub Date : 2026-07-01 eCollection Date: 2026-09-22 DOI: 10.1039/d6pm00136j
Elina Tanskanen, Hongning Sun, Kai-Chun Cheng, Jun Ishihara, Asha K Patel
{"title":"Co-formulation of IL-12 mRNA and doxorubicin in polymeric nanoparticles for simultaneous delivery in murine melanoma.","authors":"Elina Tanskanen, Hongning Sun, Kai-Chun Cheng, Jun Ishihara, Asha K Patel","doi":"10.1039/d6pm00136j","DOIUrl":"10.1039/d6pm00136j","url":null,"abstract":"<p><p>Liposomal or polymeric nanoparticles have been instrumental in improving the delivery of poorly soluble chemotherapeutics and those with dose limiting toxicity such as doxorubicin (DOX). More recently, nanoformulations have been shown to enable simultaneous delivery of emerging biomolecules such as siRNA. However, for larger nucleic acids such as mRNA, this remains challenging. In this study, we developed a poly(β-amino ester) (PBAE) based platform, capable of co-formulating mRNA and doxorubicin into nanoparticles. To demonstrate proof of concept using therapeutically relevant cargo, immunomodulatory interleukin-12 (IL-12) was selected as a model mRNA. IL-12 is a pro-inflammatory cytokine that promotes anti-tumour immunity partly through amplifying effector cytokines such as interferon-γ (IFNγ). We found that PBAE complexed DOX and mRNA into positively charged nanoparticles of 120 nm and size-exclusion chromatography indicated a DOX loading efficiency of over 97%. Co-association of both DOX and mRNA was characterised at a single nanoparticle level by nano-flow cytometry. Following delivery to B16F10 murine melanoma cells, more than 95% of cells were double-positive for DOX and Cy5-labelled mRNA, and confocal microscopy confirmed co-localised regions of DOX with mRNA. Interestingly, nanoformulated DOX had increased nuclear accumulation by 1.7-fold relative to free DOX, which correlated with a significantly reduced cell viability of 12.9% with PBAE-DOX/mRNA, compared to 26.6% for free DOX at the same dose. Moreover, despite this strong cytotoxic effect, reporter mRNA translation remained robust, with luciferase expression approximately two orders of magnitude above non-transfected controls at the highest DOX doses. Co-formulation of <i>IL-12</i> mRNA and DOX with PBAE demonstrated effective IL-12 protein secretion in transfected B16F10 cells with a simultaneous DOX dose dependent reduction in viability. Secreted IL-12 was bioactive, inducing dose-dependent STAT4 phosphorylation and IFNγ secretion in primary mouse splenocytes. Furthermore, in a syngeneic melanoma mouse model, intratumoural administration of PBAE-DOX/<i>IL-12</i> mRNA achieved significantly elevated levels of IL-12 and IFNγ in the tumour compared to the saline control, confirming delivery of DOX, as well as IL-12 protein secretion, and immunostimulatory activity <i>in vivo</i>. These findings demonstrate that PBAE is a promising platform for co-delivery of cytokine encoded mRNA with DOX in a single formulation, establishing feasibility for advanced chemoimmunotherapy approaches.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":"1266-1279"},"PeriodicalIF":5.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13370319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148458318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dual-adjuvant mucosal vaccine leveraging mast cell and TLR9 agonists for protection against poxvirus infection. 利用肥大细胞和TLR9激动剂的双佐剂粘膜疫苗对痘病毒感染的保护作用。
IF 5.5
RSC Pharmaceutics Pub Date : 2026-06-04 eCollection Date: 2026-07-21 DOI: 10.1039/d5pm00380f
Connor T Murphy, Grace L Williamson, Luis Ontiveros-Padilla, Aaron T Hendricksen, Brandi T Johnson-Weaver, Hae Woong Choi, David M Gooden, Santhosh Kalpathy, Alexandra M Lopez, Erik S Pena, Jacob M Bachelder, Rani S Sellers, Soman N Abraham, Herman F Staats, Kristy M Ainslie
{"title":"Dual-adjuvant mucosal vaccine leveraging mast cell and TLR9 agonists for protection against poxvirus infection.","authors":"Connor T Murphy, Grace L Williamson, Luis Ontiveros-Padilla, Aaron T Hendricksen, Brandi T Johnson-Weaver, Hae Woong Choi, David M Gooden, Santhosh Kalpathy, Alexandra M Lopez, Erik S Pena, Jacob M Bachelder, Rani S Sellers, Soman N Abraham, Herman F Staats, Kristy M Ainslie","doi":"10.1039/d5pm00380f","DOIUrl":"10.1039/d5pm00380f","url":null,"abstract":"<p><p>Mast cells (MC) are innate immune cells that are predominantly localized under the skin and at mucosal surfaces, and play a role in numerous physiological processes, including host response to pathogens. Recently, mast cell activators (MCA) have been identified as mucosal vaccine adjuvants that are able to promote a strong and antigen-specific immune response. We performed an extensive structure-activity relationship (SAR) analysis on the previously identified small molecule MCA, ST101036, to further optimize its adjuvanticity. This led to the development of the derivative, VAP-1185, which demonstrated improved mast cell degranulation activity <i>in vitro</i>, and a Th2-biased <i>in vivo</i> immune response. While mucosal vaccines with a single adjuvant have shown effectiveness, combining two adjuvants can activate multiple immune pathways, leading to a stronger and more comprehensive immune response. Additionally, dual adjuvant vaccines can elicit a balanced Th1/Th2 response, leading to equally effective cellular and humoral responses. We combined VAP-1185 with the FDA-approved adjuvant, cytosine phosphoguanine (CpG), which activates toll-like receptor 9 (TLR9) and promotes a Th1-biased immune response. This dual adjuvant formulation promotes inflammatory cytokine production <i>in vitro</i>, additive humoral effects and an active cellular response <i>in vivo</i>, as well as a favorable safety profile when intranasally administered to C57BL/6 mice. Subsequently, this adjuvant formulation was also able to confer protection against a lethal challenge of vaccinia virus in BALB/c mice. Thus, we report a novel mucosal vaccine formulation that produces an effective Th1/Th2 balanced immune response.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":"1022-1033"},"PeriodicalIF":5.5,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148229984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nanoparticle vaccine formulations for dengue virus. 登革热病毒纳米颗粒疫苗配方。
IF 5.5
RSC Pharmaceutics Pub Date : 2026-06-02 eCollection Date: 2026-07-21 DOI: 10.1039/d6pm00015k
Connor T Murphy, Kristy M Ainslie
{"title":"Nanoparticle vaccine formulations for dengue virus.","authors":"Connor T Murphy, Kristy M Ainslie","doi":"10.1039/d6pm00015k","DOIUrl":"10.1039/d6pm00015k","url":null,"abstract":"<p><p>Dengue virus (DENV) is one of the most prevalent mosquito-borne pathogens, with almost half of the global population at risk of infection. While most cases are mild, severe illness and even death is not uncommon. There are currently a lack of available antivirals and highly effective prophylactic vaccines available for DENV, leading to a significant gap in protection. While live-attenuated vaccines have been developed and briefly utilized, some have been found to increase the risk for developing antibody-dependent enhancement (ADE), a phenomenon that can worsen outcomes in those who are exposed to DENV after receiving the vaccination. Nanoparticle-based vaccine formulations provide numerous advantages over live-attenuated vaccines such as controlled release, dose-sparing, and ability to effectively encapsulate adjuvants and viral antigens, while simultaneously minimizing the risk for development of ADE. Numerous carrier systems have been developed, including polymeric, lipid, inorganic, and protein-based formulations. Each system has been found to induce unique antigen-specific immune activation that includes varying degrees of humoral and cellular immune responses. While there is still much research to be done, nanoparticle-based vaccine formulations offer a promising approach to combat the growing threat of DENV.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":"935-954"},"PeriodicalIF":5.5,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13238229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信
小红书