POLYMER INTERNATIONAL
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2022
·Vol. 71
·期 10
·1220-1229
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IF 3.213
Jingjing Xiao,Yingying Lu,Lu Deng,Wulian Chen,Weiguo Hu,Yuqing Zhao,Shouzhen Chen
The preparation of polymer therapeutics capable of synergistic co-delivery systems for chemotherapeutic drugs and genes remains a tough problem in cancer therapy. Herein, we develop a novel co-delivery system for chemotherapeutic drugs and genes. Paclitaxel (PTX) was covalently grafted onto the cationic copolymer poly(ethylene glycol)- b -poly( l -lysine) (PEG- b -PLL) via a disulfide bond, and then CXCL1 shRNA was loaded on the cationic micelles PEG- b -PLL-SS-PTX by electrostatic interaction to construct PEG- b -PLL-SS-PTX/pDNA complex. The chemical structure of the complex was confirmed by gel permeation chromatography, 1 H NMR and Fourier transform infrared spectroscopy. The binding ability of the cationic micelles and pDNA was detected by gel retardation assay. In vitro gene transfection studies revealed an enhanced gene transfection efficiency due to the co-delivery of PTX and pDNA to ovarian cancer cells. In vitro and in vivo data demonstrated that the co-delivery complex exhibited a synergistic role of chemotherapy and gene therapy and possessed enhanced antitumor effects. The strategy of using drug-loaded cationic micelles as gene delivery carriers is a versatile approach to construct a co-delivery system, which might result in more efficient cancer therapy. © 2022 Society of Industrial Chemistry.
研究领域:
肿瘤学
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药剂学
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分子生物学
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DOI
高影响因子
ACS Omega
·
2024
·
IF 3.7
Hua Yang,Yuerui Yang,Jiao Wang,Zhi Dong,Jiali Wang,Yuhua Ma,Peng Zhang,Wenping Wang
The codelivery of multiple bioactive phytochemicals via nano/microparticles (NPs/MPs) represents a promising strategy for enhancing therapeutic efficacy. This study presents the development of novel poly(vinyl alcohol) (PVA)-stabilized hybrid particles designed for codelivery of palmatine hydrochloride (PAL) and glycyrrhizic acid (GL). Employing a straightforward coassembly method, we synthesized dual-drug particles achieving a high payload capacity of over 70%. The particles were characterized as uniform in size, within the nano/micron range, and exhibited a ζ-potential of −5.0 mV. The incorporation of PVA not only stabilized the particles but also refined the aggregation process, resulting in more uniform and finer particles approximately 1 μm in size. Spectral analysis and molecular dynamics simulations verified the presence of π–π stacking and hydrogen bonding between PAL and GL within the particles. In vitro antibacterial assays indicated that the hybrid particles had a lower minimum inhibitory concentration against Escherichia coli and Multidrug-Resistant Staphylococcus aureus than those of the pure drugs. In vivo biodistribution study in rats revealed that the PVA-stabilized particles revealed enhanced targeting to the liver, lung, and heart, demonstrating improved tissue selectivity compared with the solution group. In summary, the PVA-stabilized hybrid NPs/MPs represent an innovative and efficient platform for codelivery of multidrugs. These findings highlight the promise of coassembled particles for high loading, enhanced bioactivity, and targeted delivery, making them a strong candidate for future clinical applications.
研究领域:
药剂学
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微生物学
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生物材料
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
·
IF 13.2
Junya Lu,Shuaipeng Feng,Zhu Liu,Yan Xiao,Hui Zhang,Siling Wang,Qinfu Zhao
The notably heightened copper levels found in cancer underscore the critical involvement of copper ions in tumor progression and metastasis. Consequently, disrupting tumor copper homeostasis is emerging as a novel strategy for cancer treatment. Here, LTMP was constructed using PEG-modified mesoporous polydopamine (MP) loaded with lonidamine (LND, a glycolysis inhibitor) and tetrathiomolybdate (TM, a copper chelator). The utilization of TM as a copper chelator led to a substantial reduction in copper content and inhibited the activity of copper-dependent enzymes, thereby suppressing the oxidative phosphorylation (OXPHOS) process in tumor cells. However, the inhibition of OXPHOS lead to compensatory upregulation of glycolysis, enhancing cellular drug resistance. Therefore, the combination of LND and TM could effectively achieve dual inhibition of glycolysis and OXPHOS, resulting in a substantial enhancement of tumor cell apoptosis. Furthermore, LTMP was found to inhibit the activities of matrix metalloproteinases and lysyl oxidase, thereby impeding the epithelial-mesenchymal transition process and significantly reducing lung tumor metastasis. Additionally, LTMP-based photothermal therapy combined with chemotherapy effectively regulated the tumor microenvironment by reducing immunosuppressive cells and enhancing T lymphocyte infiltration. This work provided new insights for the design of intricate anti-tumor strategies.
研究领域:
肿瘤学
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生物无机化学
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药物递送系统
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代谢调控
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转化医学
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产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Teng Chen,Yue Zhu,Ziyu Tang,Xingchu Gong,Jie Zhao,Jing Yang,Zhiyong Chen,Tingting Hu,Shuang Yan,Ying Zhou,Zuhua Wang
Skin scarring after injury represents a global challenge, imposing significant impacts on patients' appearance, function, and mental health, thus highlighting the clinical urgency of exploring scar prevention strategies. This study developed a multifunctional nanostructured lipid carrier hydrogel for promoting scarless wound healing based on the innovative concept of “Medicines and Excipients all-in-one”. Using anti-inflammatory and wound-healing Bletilla striata polysaccharide (BSP) and Blumea balsamifera oil (BBO) as functional excipients, we prepared integrated BBO-BSP nanostructured lipid carriers (NLC). Here, BSP served as a natural polymeric emulsifier, while BBO served as the active liquid oil. Furthermore, with BSP as the gel matrix, BBO-BSP NLC hydrogel (NLCG) were constructed, and then curcumin was loaded to form Cur@BBO-BSP NLCG, achieving the synergistic wound-healing function of multiple components. Characterization showed that Cur@BBO-BSP NLC had an average particle size of 172.6 ± 1.0 nm, a polydispersity index of 0.106 ± 0.037, an entrapment efficiency of 89.52 ± 2.28 %, and a drug loading capacity of 4.73 ± 0.08 %. Cur@BBO-BSP NLCG significantly enhanced curcumin stability, exhibiting sustained release over 264 h in vitro . Antioxidant assays revealed that Cur@BBO-BSP NLCG scavenged DPPH and hydroxyl radicals at rates of 94.10 ± 3.24 % and 94.88 ± 4.03 %, respectively, while demonstrating good biosafety and promoting L929 cell migration. In vivo experiments in rabbit ear models confirmed that Cur@BBO-BSP NLCG accelerated wound healing and inhibited scar formation. The mechanism may be related to its ability to regulate the expression of factors such as CD31, VEGF, TNF-α, IL-6, and TGF-β 1 , thereby enabling multidimensional regulation of vascular remodeling, inflammatory microenvironment and fibroblast function. The proposed “functional excipient-active medicine” collaborative delivery strategy offers a promising new paradigm for scarless wound healing therapy.
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DOI
PubMed
高影响因子
ACS Applied Polymer Materials
·
2025
·
IF 4.7
Xinyi Tang,Abiao Li,Xiaohong Cheng,Ruyi Ren,Tiange Zhao,Xiaoli Zhang,Tianqi Qin,Zhiyong Cui,Yuanyuan Ding,Chenguang Liu
Oral probiotics are a multitarget regulatory strategy for treating ulcerative colitis (UC), but their viability is mainly affected by gastric acid and reactive oxygen species (ROS). Herein, a pH and ROS dual-responsive alginate-based hydrogel facilitating the delivery of epigallocatechin gallate (EGCG)-Mn nanoparticle-modified Lacticaseibacillus rhamnosus GG (LGG@EGCG-Mn) to the colon is constructed to treat UC. EGCG-Mn layer enhances LGG’s oxidative stress resistance by 6.28-fold. The dual-responsive alginate/thioketal hydrogel (SA-tK-Ca2+) protects LGG@EGCG-Mn from gastric acid with a 71.6% survival rate and releases it at colonic lesions, resulting in improved LGG@EGCG-Mn colon retention. In vivo, LGG@EGCG-Mn@SA-tK-Ca2+ effectively prevents and treats UC by increasing the expression of ZO-1 and Occludin to restore the intestinal barrier, mitigating colon inflammation, maintaining intestinal homeostasis, and facilitating the synthesis of short-chain fatty acids. This study overcomes the challenges of probiotic delivery across the barriers of harsh gastric pH and intestinal ROS, offering a more effective probiotic therapy for UC.
研究领域:
药剂学
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胃肠病学
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纳米技术
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微生物学
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药物递送
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产品关联
DOI
高影响因子
Nanomaterials
·
2018
·Vol. 8
·期 3
·167
·
IF 3.504
Muyang Yang,Lixia Yu,Ruiwei Guo,Anjie Dong,Cunguo Lin,Jianhua Zhang
Synergistic combination therapy by integrating chemotherapeutics and chemosensitizers into nanoparticles has demonstrated great potential to reduce side effects, overcome multidrug resistance (MDR), and thus improve therapeutic efficacy. However, with regard to the nanocarriers for multidrug codelivery, it remains a strong challenge to maintain design simplicity, while incorporating the desirable multifunctionalities, such as coloaded high payloads, targeted delivery, hemodynamic stability, and also to ensure low drug leakage before reaching the tumor site, but simultaneously the corelease of drugs in the same cancer cell. Herein, we developed a facile modular coassembly approach to construct an all-in-one multifunctional multidrug delivery system for the synergistic codelivery of doxorubicin (DOX, chemotherapeutic agent) and curcumin (CUR, MDR modulator). The acid-cleavable PEGylated polymeric prodrug (DOX-h-PCEC), tumor cell-specific targeting peptide (CRGDK-PEG-PCL), and natural chemosensitizer (CUR) were ratiometrically assembled into in one single nanocarrier (CUR/DOX-h[email protected]NPs). The resulting CUR/DOX-h[email protected]NPs exhibited several desirable characteristics, such as efficient and ratiometric drug loading, high hemodynamic stability and low drug leakage, tumor intracellular acid-triggered cleavage, and subsequent intracellular simultaneous drug corelease, which are expected to maximize a synergistic effect of chemotherapy and chemosensitization. Collectively, the multifunctional nanocarrier is feasible for the creation of a robust nanoplatform for targeted multidrug codelivery and efficient MDR modulation.Keywords:modular coassemble;synergistic codelivery;polymeric prodrug;stimulisensitive release;biocompatibility
研究领域:
药学
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纳米技术
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药物递送系统
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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 Nanomedicine
·
2023
·
IF 8
Weimin Fang,Jinghao Wang,Xiaocong Ma,Ni Shao,Kunlin Ye,Dong Zhang,Changzheng Shi,Liangping Luo
Background Olaparib, a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor has demonstrated promising efficacy in patients with triple-negative breast cancer (TNBC) carrying breast cancer gene (BRCA) mutations. However, its impact on BRCA wild-type (BRCAwt) TNBC is limited. Hence, it is crucial to sensitize BRCAwt TNBC cells to olaparib for effective clinical practice. Novobiocin, a DNA polymerase theta (POLθ) inhibitor, exhibits sensitivity towards BRCA-mutated cancer cells that have acquired resistance to PARP inhibitors. Although both of these DNA repair inhibitors demonstrate therapeutic efficacy in BRCA-mutated cancers, their nanomedicine formulations’ antitumor effects on wild-type cancer remain unclear. Furthermore, ensuring effective drug accumulation and release at the cancer site is essential for the clinical application of olaparib.Materials and Methods Herein, we designed a progressively disassembled nanosystem of DNA repair inhibitors as a novel strategy to enhance the effectiveness of olaparib in BRCAwt TNBC. The nanosystem enabled synergistic delivery of two DNA repair inhibitors olaparib and novobiocin, within an ultrathin silica framework interconnected by disulfide bonds.Results The designed nanosystem demonstrated remarkable capabilities, including long-term molecular storage and specific drug release triggered by the tumor microenvironment. Furthermore, the nanosystem exhibited potent inhibitory effects on cell viability, enhanced accumulation of DNA damage, and promotion of apoptosis in BRCAwt TNBC cells. Additionally, the nanosystem effectively accumulated within BRCAwt TNBC, leading to significant growth inhibition and displaying vascular regulatory abilities as assessed by magnetic resonance imaging (MRI).Conclusion Our results provided the inaugural evidence showcasing the potential of a progressively disassembled nanosystem of DNA repair inhibitors, as a promising strategy for the treatment of BRCA wild-type triple-negative breast cancer.
研究领域:
肿瘤学
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药学
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纳米技术
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癌症生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）