journal
https://read.qxmd.com/read/36948420/sting-agonist-loaded-mesoporous-manganese-silica-nanoparticles-for-vaccine-applications
#1
JOURNAL ARTICLE
Cheng Xu, Hannah E Dobson, Mengjie Yu, Wang Gong, Xiaoqi Sun, Kyung Soo Park, Andrew Kennedy, Xingwu Zhou, Jin Xu, Yao Xu, Andrew W Tai, Yu Leo Lei, James J Moon
Cyclic dinucleotides (CDNs), as one type of Stimulator of Interferon Genes (STING) pathway agonist, have shown promising results for eliciting immune responses against cancer and viral infection. However, the suboptimal drug-like properties of conventional CDNs, including their short in vivo half-life and poor cellular permeability, compromise their therapeutic efficacy. In this study, we have developed a manganese-silica nanoplatform (MnOx @HMSN) that enhances the adjuvant effects of CDN by achieving synergy with Mn2+ for vaccination against cancer and SARS-CoV-2...
March 20, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36948419/bioorthogonal-nanozymes-for-breast-cancer-imaging-and-therapy
#2
JOURNAL ARTICLE
Xianzhi Zhang, Yuanchang Liu, Jeerapat Doungchawee, Laura J Castellanos-García, Kristen N Sikora, Taewon Jeon, Ritabrita Goswami, Stefano Fedeli, Aarohi Gupta, Rui Huang, Cristina-Maria Hirschbiegel, Roberto Cao-Milán, Prabin K D Majhi, Yagiz Anil Cicek, Liang Liu, D Joseph Jerry, Richard W Vachet, Vincent M Rotello
Bioorthogonal catalysis via transition metal catalysts (TMCs) enables the generation of therapeutics locally through chemical reactions not accessible by biological systems. This localization can enhance the efficacy of anticancer treatment while minimizing off-target effects. The encapsulation of TMCs into nanomaterials generates "nanozymes" to activate imaging and therapeutic agents. Here, we report the use of cationic bioorthogonal nanozymes to create localized "drug factories" for cancer therapy in vivo...
March 20, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36948418/nanoassembly-with-self-regulated-magnetic-thermal-therapy-and-controlled-immuno-modulating-agent-release-for-improved-immune-response
#3
JOURNAL ARTICLE
Maoyu Gao, Kai Feng, Xinmiao Zhang, Yiling Ruan, Guizhen Zhao, Huihui Liu, Xiaolian Sun
Cancer immunotherapy is an emerging cancer therapeutic method by activating the patient's immune system but suffers from low immunogenicity at tumor sites. Fever-like heat is known to modulate an immune-friendly tumor microenvironment. Here, temperature-responsive iron oxide nanoassemblies (IONAs) are developed by crosslinking iron oxide nanoparticles (IONPs) and loaded with JQ1 (JQ1/IONAs), a molecular drug known to down-regulate PD-L1. In the presence of an alternating magnetic field (AMF), the IONAs demonstrate a much more effective magnetic thermal effect than IONPs and are responsively disassembled to prevent overheating...
March 20, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36940774/a-self-amplified-ferroptosis-nanoagent-that-inhibits-the-tumor-upstream-glutathione-synthesis-to-reverse-cancer-chemoresistance
#4
JOURNAL ARTICLE
Chuang Yang, Zheng Chen, Min Wei, Shen Hu, Mengyuan Cai, Nan Wang, Yunan Guan, Fangyuan Li, Qiang Ding, Daishun Ling
Ferroptosis has recently become an attractive strategy to combat the chemoresistance of cancer cells, but the intracellular ferroptosis defense system greatly challenges the efficient ferroptosis induction. Herein, we report a ferrous metal-organic framework-based nanoagent (FMN) that inhibits the intracellular upstream glutathione synthesis and induces self-amplified ferroptosis of cancer cells, for reversing chemoresistance and boosting chemotherapy. The FMN is loaded with SLC7A11 siRNA (siSLC7A11) and chemotherapeutic doxorubicin (DOX), which shows enhanced tumor cell uptake and retention, thus ensuring the effective DOX delivery and tumor intracellular iron accumulation...
March 18, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36940773/predetermination-of-burst-times-of-elastoplastic-osmotic-capsules
#5
JOURNAL ARTICLE
Krutika Meena Harish Jain, Ronald A Siegel
"Pulsed drug release" for dosing drugs such as vaccines, hormones etc. that require multiple, pre-determined release events can be obtained by using capsules that exploit the principle of osmosis to achieve a delayed-burst release of their payload. An objective of this study was to precisely determine the lag-time before burst which occurs when the hydrostatic pressure developed due to water influx expands the capsule shell to rupture. A novel 'dip-coating' technique was used to encapsulate osmotic agent solution or solid within biodegradable poly(lactic acid-co-glycolic) (PLGA) spherical capsule shells...
March 18, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36918085/precise-and-systematic-end-group-chemistry-modifications-on-pamam-and-poly-l-lysine-dendrimers-to-improve-cytosolic-delivery-of-mrna
#6
JOURNAL ARTICLE
Fanny Joubert, Michael J Munson, Alan Sabirsh, Richard M England, Martin Hemmerling, Cameron Alexander, Marianne B Ashford
Here, we aimed to chemically modify PAMAM dendrimers using lysine as a site-selective anchor for successfully delivering mRNA while maintaining a low toxicity profile. PAMAM dendrimers were multi-functionalised by amidation reactions in a regioselective, quantitative and stepwise manner with carefully selected property-modifying surface groups. Alternatively, novel lysine-based dendrimers were prepared in the same manner with the aim to unlock their potential in gene delivery. The modified dendrimers were then formulated with Cy5-EGFP mRNA by bulk mixing via liquid handling robotics across different nitrogen to phosphate ratios...
March 17, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36933701/hif-1-inhibitor-based-one-stone-two-birds-strategy-for-enhanced-cancer-chemodynamic-immunotherapy
#7
JOURNAL ARTICLE
Xiaojuan Zhang, Chuanchuan He, Xuelian He, Sijun Fan, Baoyue Ding, Yao Lu, Guangya Xiang
Based on its ability to induce strong immunogenic cell death (ICD), chemodynamic therapy (CDT) was elaborately designed to combine with immunotherapy for a synergistic anticancer effect. However, hypoxic cancer cells can adaptively regulate hypoxia-inducible factor-1 (HIF-1) pathways, leading to a reactive oxygen species (ROS)-homeostatic and immunosuppressive tumor microenvironment. Consequently, both ROS-dependent CDT efficacy and immunotherapy are largely diminished, further lowering their synergy. Here, a liposomal nanoformulation co-delivering a Fenton catalyst copper oleate and a HIF-1 inhibitor acriflavine (ACF) was reported for breast cancer treatment...
March 16, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36933700/an-efficient-nano-silica-in-glucan-particles-protein-encapsulation-approach-for-improved-thermal-stability
#8
JOURNAL ARTICLE
Ernesto R Soto, Charles A Specht, Florentina Rus, Chrono K Lee, Ambily Abraham, Stuart M Levitz, Gary R Ostroff
Glucan particles (GPs) are hollow, porous microspheres derived from Saccharomyces cerevisiae (Baker's yeast). The hollow cavity of GPs allows for efficient encapsulation of different types of macromolecules and small molecules. The β-1,3-D-glucan outer shell provides for receptor-mediated uptake by phagocytic cells expressing β-glucan receptors and uptake of particles containing encapsulated proteins elicit protective innate and acquired immune responses against a wide range of pathogens. A limitation of the previously reported GP protein delivery technology is limited protection from thermal degradation...
March 16, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36933699/crgd-targeted-heparin-nanoparticles-for-effective-dual-drug-treatment-of-cisplatin-resistant-ovarian-cancer
#9
JOURNAL ARTICLE
Xiaomei Liang, Yulu Yang, Chuanqing Huang, Zhibin Ye, Wujiang Lai, Jiamao Luo, Xiaoxuan Li, Xiao Yi, Jun-Bing Fan, Ying Wang, Yifeng Wang
Resistance to the chemotherapeutic agent cisplatin (DDP) is the primary reason for invalid chemotherapy of ovarian cancer. Given the complex mechanisms underlying chemo-resistance, the design of combination therapies based on blocking multiple mechanisms is a rationale to synergistically elevate therapeutic effect for effectively overcoming cancer chemo-resistance. Herein, we demonstrated a multifunctional nanoparticle ([email protected]), which could simultaneously co-deliver DDP and Olaparib (Ola, DNA damage repair inhibitor) using targeted ligand cRGD peptide modified with heparin (HR) as nanocarrier, enabling the concurrent tackling of multiple resistance mechanisms to effectively inhibit the growth and metastasis of DDP-resistant ovarian cancer...
March 16, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36931471/quantitative-pet-tracking-of-intra-articularly-administered-89-zr-peptide-decorated-nanoemulsions
#10
JOURNAL ARTICLE
Sandra Díez-Villares, Lara García-Varela, Soraya Groba-de Antas, José Ramón Caeiro, Paula Carpintero-Fernandez, María D Mayán, Pablo Aguiar, María de la Fuente
Intra-articular (IA) administration of drugs for the treatment of diseases such as rheumatoid arthritis, osteoarthritis and psoriatic arthritis is a common strategy; however, the rapid clearance from the synovial fluid restricts their effectivity due to the limited retention time. Drug Delivery Systems (DDS) are currently being developed to increase their joint retention time. This study compares the biodistribution and retention time of a senolytic peptide (PEP), with potential application in osteoarthritis disease, and this senolytic peptide encapsulated in a DDS based on a lipid nanoemulsion (PEPNE) by using positron emission tomography (PET) imaging...
March 15, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36931470/smo-crispr-mediated-apoptosis-in-cd133-targeted-cancer-stem-cells-and-tumor-growth-inhibition
#11
JOURNAL ARTICLE
Shambhavi Pandey, Myungchul Lee, Jaewoon Lim, Sangbae Park, Yun-Hoon Choung, Jae Eun Kim, Pankaj Garg, Jong Hoon Chung
Cancer stem cells (CSCs) possess the ability to indefinitely proliferate and resist therapy, leading to cancer relapse and metastasis. To address this, we aimed to develop a CSC-inclusive therapy that targets both CSCs and non-CSC glioblastoma (GBM) cells. We accomplished this by using a smoothened (SMO) CRISPR/Cas9 plasmid to suppress the hedgehog pathway in CSCs, in combination with inhibiting the serine hydroxymethyl transferase 1 (SHMT1)-driven thymidylate biosynthesis pathway in non-CSC GBM cells using SHMT1 siRNA (siSHMT1)...
March 15, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36907564/oral-lymphatic-delivery-of-alpha-galactosylceramide-and-ovalbumin-evokes-anti-cancer-immunization
#12
JOURNAL ARTICLE
Prashant Pandey, Seung Hyun Kim, Laxman Subedi, Khizra Mujahid, Yebon Kim, Young-Chang Cho, Jung-Hyun Shim, Ki-Taek Kim, Seung-Sik Cho, Jeong Uk Choi, Jin Woo Park
We developed an orally delivered nanoemulsion that induces cancer immunization. It consists of tumor antigen-loaded nano-vesicles carrying the potent invariant natural killer T-cell (iNKT) activator α-galactosylceramide (α-GalCer), to trigger cancer immunity by effectively activating both innate and adaptive immunity. It was validated that adding bile salts to the system boosted intestinal lymphatic transport as well as the oral bioavailability of ovalbumin (OVA) via the chylomicron pathway. To increase intestinal permeability further and amplify the antitumor responses, an ionic complex of cationic lipid 1,2-dioleyl-3-trimethylammonium propane (DTP) with sodium deoxycholate (DA) (DDP) and α-GalCer were anchored onto the outer oil layer to form OVA-NE#3...
March 15, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36924897/biomimetic-gene-editing-system-for-precise-tumor-cell-reprogramming-and-augmented-tumor-therapy
#13
JOURNAL ARTICLE
Lei Qiao, Min Gao, Xiaoqing Yi, Hui Peng, Ruijie Zhang, Wanqing Yao, Gengyun Sun, Xiaoyan He
The abnormal level of hypoxia-inducible factor-1 alpha (HIF-1α) is closely related to cancer metastasis and treatment resistance. CRISPR-Cas9-based gene editing technology has sparked profound hope to solve this issue by precise gene disruption, although the in vivo application remains hindered by the lack of a safe and efficient delivery strategy. Herein, we developed a cell membrane biomimetic core-shell system for light-controllable, precise gene editing. The inner core of the system comprises protamine for CRISPR-Cas9/sgRNA plasmid (pCas9) loading and calcium ions for efficient pCas9 transfection...
March 14, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36924896/smart-anti-vascular-nanoagent-induces-positive-feedback-loop-for-self-augmented-tumor-accumulation
#14
JOURNAL ARTICLE
Mengting Du, Tingting Geng, Rongrong Yu, Gang Song, Hui Cheng, Yu Cao, Weidong He, Abdul Haleem, Qinglin Li, Rongfeng Hu, Shengqi Chen
How to achieve efficient drug accumulation in the tumor with low vascular density is a great challenge but the key to push the limit of anti-vascular therapeutic efficacy. Herein, we report a charge-reversible nanoparticles of gambogenic acid (CRNP-GNA) that would induce the positive feedback loop between increased tumor vascular permeability and improved drug accumulation. This positive feedback loop would remarkably improve tumor vascular permeability for efficient drug accumulation through few residue vessels...
March 14, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36924895/differentiation-therapy-for-murine-myelofibrosis-model-with-mln8237-loaded-low-density-lipoproteins
#15
JOURNAL ARTICLE
Binghong He, Chao Wang, Fuping Wang, Liang Tian, Haitao Wang, Chunling Fu, Jin Liu, Chao Xi, Chunlei Zhu, Qiong Yang
Primary myelofibrosis (PMF) is a severe myeloproliferative neoplasm that is characterized by low-differentiation megakaryoblasts and progressive bone marrow fibrosis. Although an Aurora kinase A (AURKA) targeting small-molecule inhibitor MLN8237 has been approved in clinical trials for differentiation therapy of high-risk PMF patients, its off-target side effects lead to a partial remission and serious complications. Here, we report a dual-targeting therapy agent (rLDL-MLN) with great clinical translation potential for differentiation therapy of PMF disease...
March 14, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36924894/charge-conversional-click-polyprodrug-nanomedicine-for-targeted-and-synergistic-cancer-therapy
#16
JOURNAL ARTICLE
Yupeng Wang, Yuwei Cong, Manying Cai, Xiaoling Liang, Lina Wang, Dongfang Zhou
Polyprodrug nanomedicines hold great potential for combating tumors. However, the functionalization of polyprodrug nanomedicines to improve therapeutic efficacy is restricted by conventional polymerization methods. Herein, we fabricated a charge-conversional click polyprodrug nanomedicine system by metal-free azide-alkyne cycloaddition click polymerization (AACCP) for targeted and synergistic cancer therapy. Specifically, Pt(IV) prodrug-backboned diazide monomer, DMC prodrug-pendent diazide monomer, dialkyne-terminated PEG monomer and azide-modified folate were click polymerized to obtain the target polyprodrug (P1)...
March 14, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36921725/targeted-sirna-lipid-nanoparticles-for-the-treatment-of-kras-mutant-tumors
#17
JOURNAL ARTICLE
Shubaash Anthiya, Süleyman Can Öztürk, Hamdullah Yanik, Ece Tavukcuoglu, Adem Sahin, Dhrubajyoti Datta, Klaus Charisse, David Moreira Álvarez, Mabel Loza, Alfonso Calvo, Einar Sulheim, Simon Loevenich, Geir Klinkenberg, Ruth Schmid, Muthiah Manoharan, Güneş Esendağlı, Maria Jose Alonso
K-RAS is a highly relevant oncogene that is mutated in approximately 90% of pancreatic cancers and 20-25% of lung adenocarcinomas. The aim of this work was to develop a new anti-KRAS siRNA therapeutic strategy through the engineering of functionalized lipid nanoparticles (LNPs). To do this, first, a potent pan anti-KRAS siRNA sequence was chosen from the literature and different chemical modifications of siRNA were tested for their transfection efficacy (KRAS knockdown) and anti-proliferative effects on various cancer cell lines...
March 13, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36921724/studying-spatial-drug-distribution-in-golf-ball-shaped-microspheres-to-understand-drug-release
#18
JOURNAL ARTICLE
Ying Xue, Lixiao Xu, Aiping Wang, Yongchao Ma, Wei Zhang, Wei Ji, Guangyi Leng, Fengmei Zhou, Wanhui Liu, Xin Di
Poly (lactic-co-glycolic acid) (PLGA) microspheres have been one of the most successful products for slow drug release. While distribution of drugs in microspheres might be a fundamental factor affecting drug release, it has been often overlooked. Indeed, very few studies are available on the distribution of drugs in microspheres with complex morphology, like e.g. golf ball-shaped microspheres. In this paper, the distribution of rotigotine in golf ball-shaped microspheres (GSRM) was investigated by argon ion milling, combined with scanning electron microscopy and energy dispersive X-ray spectroscopy (AIM-SEM-EDS)...
March 13, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36921723/preventing-ischemia-reperfusion-injury-by-acousto-mechanical-local-oxygen-delivery
#19
JOURNAL ARTICLE
Yi-Ju Ho, Hui-Ching Hsu, Bing-Huan Wu, Yu-Chun Lin, Lun-De Liao, Chih-Kuang Yeh
Ischemia-reperfusion (I/R) injury is a pathological process that causes vascular damage and dysfunction which increases recurrence and/or mortality in myocardial infarction, ischemic stroke, and organ transplantation. We hypothesized that ultrasound-stimulated oxygen-loaded microbubble (O2 -MB) cavitation would enhance mechanical force on endothelium and simultaneously release oxygen locally at the targeted vessels. This cooperation between biomechanical and biochemical stimuli might modulate endothelial metabolism, providing a potential clinical approach to the prevention of I/R injury...
March 13, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36921722/hyaluronan-nanoplatelets-exert-an-intrinsic-anti-inflammatory-activity-in-a-rat-model-of-bladder-painful-syndrome-interstitial-cystitis
#20
JOURNAL ARTICLE
Raul Diaz-Salmeron, Catherine Cailleau, Stéphanie Denis, Gilles Ponchel, Kawthar Bouchemal
Glycosaminoglycan (GAG) replenishment therapy consists of the instillation of GAG solutions directly in the bladder to alleviate Bladder Painful Syndrome/Interstitial Cystitis (BPS/IC). However, several issues were reported with this strategy because the GAG solutions are rapidly eliminated from the bladder by spontaneous voiding, and GAG have low bioadhesive behaviors. Herein, GAG nanomaterials with typical flattened morphology were obtained by a self-assembly process. The formation mechanism of those nanomaterials, denoted as nanoplatelets, involves the interaction of α-cyclodextrin cavity and alkyl chains covalently grafted on the GAG...
March 13, 2023: Journal of Controlled Release
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