COLLOIDS AND SURFACES B-BIOINTERFACES
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2020
·
IF 4.389
Muhammad Asim Farooq,Huang Xinyu,Amna Jabeen,Anam Ahsan,Theodora Amanda Seidu,Perpetua Takunda Kutoka,Bo Wang
Vorinostat (VOR) is known as one of the histone deacetylase inhibitors (HDACi) for cancer treatment, and the FDA approves it for cutaneous T cell lymphoma therapy. Poor solubility, permeability, and less anti-cancer activity are the main challenges for the effective delivery of VOR against various cancers. So, our team assumed that the surface-coated liposomes might improve the physicochemical properties of biopharmaceutics classification system class IV drugs such as VOR. The present study aimed to enhance the cytotoxicity and improve cellular uptake using TPGS-coated liposomes in breast cancer cells. Liposomes were fabricated by the film hydration following the probe ultra-sonication method. OR-LIPO and TPGS-VOR-LIPO showed an average particle size of 211.97 ± 3.42 nm with PDI 0.2168 ± 0.006 and 176.99 ± 2.06 nm with PDI 0.175 ± 0.018, respectively. TPGS-coated liposomes had better stability and revealed more than 80 % encapsulation efficiency than conventional liposomes. Transmission electron microscopy confirmed the TPGS coating around liposomes. Moreover, TPGS-coated liposomes enhanced the solubility and showed sustained release of VOR over 48 h. DSC and PXRD analysis also reveal an amorphous state of VOR within the liposomal formulation. MTT assay result indicates that the superior cytotoxic effect of surface-modified liposomes contrasts with the conventional and free VOR solution, respectively. Fluorescence microscopy and flow cytometry results also presented an enhanced cellular uptake of TPGS-coated liposomes against breast cancer cells, respectively. The current investigation's final results declared that TPGS-coated liposomes are promising drug carriers for the effective delivery of hydrophobic drugs for cancer therapy.
研究领域:
药学
·
肿瘤学
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DOI
PubMed
高影响因子
American Journal of Cancer Research
·
2024
·
IF 3.6
Xiao-Li Zheng,Zhi-Di Li,Kai-Zhi Luo,Yang-Ling Li,Ye-Han Liu,Shu-Ying Shen,Fei-Yan Shen,Wan-Yan Li,Guo-Qing Chen,Chong Zhang,Ling-Hui Zeng
Glioblastoma is the most common cancer in the brain, resistant to conventional therapy and prone to recurrence. Therefore, it is crucial to explore novel therapeutics strategies for the treatment and prognosis of GBM. In this study, through analyzing online datasets, we elucidated the expression and prognostic value of POLR2J and its co-expressed genes in GBM patients. Functional experiments, including assays for cell apoptosis and cell migration, were used to explore the effects of POLR2J and vorinostat on the proliferation and migration of GBM cells. The highest overexpression of POLR2J, among all cancer types, was observed in GBM. Furthermore, high expression of POLR2J or its co-expressed genes predicted a poor outcome in GBM patients. DNA replication pathways were significantly enriched in the GBM clinical samples with high POLR2J expression, and POLR2J suppression inhibited proliferation and triggered cell cycle G1/S phase arrest in GBM cells. Moreover, POLR2J silencing activated the unfolded protein response (UPR) and significantly enhanced the anti-GBM activity of vorinostat by suppressing cell proliferation and inducing apoptosis. Additionally, POLR2J could interact with STAT3 to promote the metastatic potential of GBM cells. Our study identifies POLR2J as a novel oncogene in GBM progression and provides a promising strategy for the chemotherapeutic treatment of GBM.
研究领域:
肿瘤学
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分子生物学
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
·
IF 5.3
Weiwei Jiang,Yuwei Cheng,Lei Hou,Ying Huang,Sizhen Wang,Yunchang Zhang,Tao Jiang,Feng Yang,Zhiqiang Ma
The challenges posed by intractable relapse and metastasis in cancer treatment have led to the development of various forms of photodynamic therapy (PDT). However, traditional drug delivery systems, such as virus vectors, liposomes, and polymers, often suffer from issues like desynchronized drug release, carrier instability, and drug leakage during circulation. To address these problems, we have developed a dual-prodrug nanogel (PVBN) consisting of Pyro (Pyropheophorbide a) and SAHA (Vorinostat) bound to BSA (Bovine Serum Albumin), which facilitates synchronous and spontaneous drug release in situ within the lysosome. Detailed results indicate that PVBN-treated tumor cells exhibit elevated levels of ROS and Acetyl-H3, leading to necrosis, apoptosis, and cell cycle arrest, with PDT playing a dominant role in the synergistic therapeutic effect. Furthermore, the anti-tumor efficacy of PVBN was validated in melanoma-bearing mice, where it significantly inhibited tumor growth and pulmonary metastasis. Overall, our dual-prodrug nanogel, formed by the binding of SAHA and Pyro to BSA and releasing drugs within the lysosome, represents a novel and promising strategy for enhancing the clinical efficacy of photochemotherapy.
研究领域:
药学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 8
·2261-2269
·
IF 5.831
Chenwei Wu,Li Xu,Leilei Shi,Xihui Gao,Jing Li,Xinyuan Zhu,Chuan Zhang
Multidrug resistance (MDR) is one of the most important reasons for the failure of clinical chemotherapy treatment of cancer patients. Although several strategies have been proposed to overcome MDR, their contributions in improving therapeutic efficacy are not adequate. Herein, we constructed a nano-twindrug using a supramolecular self-assembling strategy, with the aim of efficiently reversing MDR. Due to the supramolecular interactions, doxorubicin (DOX) and vorinostat (SAHA) could self-assemble into stable spherical nanoparticles with a size of ∼160 nm. Since the antitumor drugs were not modified by nontherapeutic drug carriers, our strategy ensured a drug-loading efficacy of 100%. Furthermore, our study revealed that the DOX-SAHA nano-twin drug could enter drug-resistant cancer cells and inhibit their proliferation more effectively in vitro than single DOX, SAHA, or a DOX/SAHA mixture. In the meantime, the DOX-SAHA nano-twin drug could accumulate at the tumor site in vivo and show higher antitumor efficacy accompanied by low side effects.
研究领域:
肿瘤学
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药剂学
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纳米医学
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癌症研究
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 7
·1103-1115
·
IF 7.571
Tao Ding,Jing Zhu,Haidi Guan,Daqing Xia,Yuxin Xing,Jixi Huang,Zhenqiang Wang,Kaiyong Cai,Jixi Zhang
A cell membrane barrier which dominates the therapeutic efficacy and systemic side effects is a major bottleneck in the field of drug delivery. Herein, a therapeutic system capable of photothermally triggered on-demand and cytosolic delivery was achieved by polydopamine (PDA) nanoparticle-stabilized colloidosomes. An organic phase change material (PCM, saturated fatty acids) was employed as the lipid core for Pickering emulsification and drug encapsulation, and arginine was utilized as a linker to induce the directional interactions between nanoemulsion droplets and heterogeneously nucleated PDA nanoparticles. Moreover, the PDA particle stabilizers concomitantly mediated the grafting of hydrophilic polymer PEG to further improve dispersibility. The resultant colloidosomes after cooling possess lowered melting points and superior dispersion stability over 7 days. When irradiated with near-infrared light (808 nm), sequential processes of fatty acid melting and direct drug perfusion into the cytosol took place within 10 min. The employment of vorinostat (SAHA, histone deacetylase inhibitor) as a model membrane-impermeable drug resulted in remarkable enhancement of anti-cancer effects both in vitro (5.2 fold reduction in IC50) and in vivo (7.3 fold increase in tumor inhibition rate) with respect to the free drug. The remotely triggered transformable nanoplatform paves a new avenue of responsive and efficient cytosolic perfusion to overcome biological membrane barriers on the basis of colloidosomes.
研究领域:
药物递送系统
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纳米技术
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癌症治疗
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材料科学
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
·
IF 4.5
Yaru Li,Qian Yang,Lanlan Fan,Fang Liu,Yaqi Shang,Baoxin Zhang,Zheng Wang,Yanjun Zhao
Ovarian cancers (OC) often resist current standard chemotherapy because of the cancer heterogeneity and over-expression of an anti-apoptotic protein, myeloid cell leukemia-1 (MCL-1). The heterogeneous OC shows impaired redox homeostasis and relies heavily on glutathione peroxidase 4 to eliminate toxic lipid peroxides. Therefore, integrated apoptosis and ferroptosis therapy is promising for OC management. The current work reports a liposomal nanosystem for apoptotic and ferroptotic OC therapy. Simvastatin (Sim) and vorinostat (Saha) were selected as the pleiotropic model drugs. The successive release of Saha and Sim from liposomes enabled the sequential amplification of MCL-1 by Saha, and then MCL-1 inhibition by Sim. Such a strategy could potently induce apoptosis in a human OC cell line (SKOV3), as indicated by increased intracellular cytochrome c concentration, caspase 3/9 activity, and the extent of apoptosis. Besides, Saha played multiple roles in cell death. It could induce cell cycle arrest at the G 2 /M phase and apoptosis. Saha also inhibited the glutamate-cystine transporter (SLC7A11) and provoked ferroptosis, which was corroborated by the depletion of glutathione, reduced nicotinamide adenine dinucleotide phosphate, and boost of lipid peroxides and malondialdehyde in SKOV3 cells. The current work integrated the “sequential amplification and inhibition of MCL-1 target” concept with combinational apoptosis and ferroptosis OC therapy, which might offer a new approach for managing resistant OC and other malignant diseases.
研究领域:
肿瘤学
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药学
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细胞生物学
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纳米技术
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）