Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 31
·6439-6447
·
IF 4.726
Ai-Zheng Chen,Yong-Qiang Kang,Shi-Bin Wang,Na Tang,Xiao-Qian Su
The co-delivery of siRNA and therapeutic agents provides an effective method for cancer chemotherapy by avoiding drug resistance during the treatment. With a combination of ionic gelation and supercritical fluid technology, nanoparticle-embedded composite microparticles (CMPs) co-loaded with siRNA and paclitaxel (siRNA-PTX-CMPs) were successfully prepared. The results show that CMPs embedded with nanoparticles with a diameter of 50–100 nm exhibited a spherical shape and core–shell structure with a mean diameter of 323 nm. The encapsulation efficiency of siRNA in chitosan nanoparticles (CS NPs) was 96.97%. The drug load and encapsulation efficiency of PTX-loaded CMPs (5% dosage) were 1.40% and 27.95%, respectively; both these increased with an increase in dosage. It was found that no change had occurred in the functional groups of the components during the supercritical process, while the physical form of PTX had shifted to an amorphous state. In the cell experiments, the CMPs clustered around the nucleus after being taken up by the Bcap-37 cells. The results of the antitumor effect experiments revealed that the co-loaded siRNA-PTX-CMPs achieved a significantly better synergistic effect than single dosages, which indicated that the co-delivery system developed by the supercritical process could have potential in the application of cancer chemotherapy.
研究领域:
药剂学
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肿瘤学
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药物递送系统
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生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2018
·
IF 4.37
Menghao Shi,Xiufeng Zhao,Jiulong Zhang,Shuang Pan,Chunrong Yang,Ying Wei,Haiyang Hu,Mingxi Qiao,Dawei Chen,Xiuli Zhao
Introduction Specific polo-like kinase (PLK1) silencing with small interface RNA (siRNA) may be an effective approach for PLK1-overexpressed lung cancer. However, low siRNA concentration into cytoplasm of tumor tissue severely limits its application. Materials and methods In this study, a novel triblock copolymer methoxy poly(ethylene glycol)-poly(histidine)-poly(sulfadimethoxine) (mPEG-PHis-PSD, shorten as PHD) was synthesized and used to construct novel nonviral gene vector with cationic liposomes. Results The resulting hybrid nanoparticles (PHD/LR) loaded with siPLK1 possessed excellent physiochemical properties. In vitro study indicated that PHD/LR could be efficiently internalized into human lung adenocarcinoma A549 cells and downregulated PLK1 protein expression to induce cell apoptosis, which was attributed to pH-induced instantaneous dissociation, efficient endo/lysosomal escape arose from PHD copolymer. Furthermore, in vivo antitumor activity demonstrated that PHD/LR could efficiently accumulated into tumor tissue and silenced PLK1 expression to possess antitumor activity. Conclusion Taken all these together, PHD/LR was expected to be a suitable carrier for specific delivering siRNA for lung cancer therapy.
研究领域:
癌症研究
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纳米技术
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药学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
·
IF 13.3
Haiping Li,Yuying Zhang,Bo Huang,Feifei Yang,Qiang Ma,Xiaolin Wang,Yuying Liu,Junwu Ren,Xiaojuan Pan,Ce Liang,Shimin Wang,Hao Ning,Changhong Qin,Yan Jiang,Ai Ran,Bin Xiao
Gastric cancer (GC) is a prevalent malignancy in China, necessitating innovative treatments. Recent advancements in nucleic acid drugs, particularly small interfering RNAs (siRNAs), have shown promise in therapeutic applications. Biodegradable layered double hydroxides (LDHs), as a class of typical two-dimensional (2D) materials, hold great prospects in biomedical and drug delivery systems. Building on our previous research, which identified the upregulated insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) promoted GC progression, we devised a strategy that leverages the unique properties of LDHs carriers with siRNA therapeutics. Herein, we synthesized CuAl-LDHs containing variable valence metal cations (Cu 2+ ), capable of inducing a Fenton-like reaction in the tumor micro-acid environment (TME) of GC. Subsequently, we constructed si-IGF2BP3/CuAl-LDHs nanocomposites to protect and deliver si-IGF2BP3 via the CuAl-LDHs carrier. The obtained nanocomposites demonstrated significant efficacy in inhibiting GC cell proliferation by silencing the IGF2BP3 gene at both the mRNA and protein levels, accelerating oxidative stress in GC cells through a Fenton-like reaction, and achieving greater suppression of tumor volume than CuAl-LDHs alone. The remarkable anti-tumor effect was attributed to the CuAl-LDHs carrier’s superior siRNA immobilization and delivery capabilities, as well as the catalytic ability of Cu in CuAl-LDHs, facilitating the Fenton-like reaction within TME. Overall, this integrated GC therapy strategy employing LDHs nano-carriers may represent a significant advancement in developing next-generation therapeutic systems. It underscores the potential of LDHs as an effective platform for targeted GC therapy.
研究领域:
肿瘤学
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纳米技术
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药物递送系统
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分子生物学
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生物医学工程
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产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2021
·Vol. 10
·期 20
·2100938
·
IF 9.933
Gaizhen Kuang,Hongtong Lu,Shasha He,Hejian Xiong,Jie Yu,Qingfei Zhang,Yubin Huang
Stimuli-responsive nanosystems have been widely applied as effective modalities for drug/gene co-delivery in cancer treatment. However, precise spatiotemporal manipulations of drug/gene co-delivery, as well as multi-modality imaging-guided cancer therapy, still remain a daunting challenge. Here, multifunctional polyprodrug/siRNA loaded upconversion nanoparticles (UCNPs) are reported that combine computed tomography (CT), magnetic resonance (MR), and upconversion luminescence (UCL) tri-modality imaging and near-infrared (NIR) light-activated drug/gene on-demand delivery. The photoactivatable platinum(IV) (Pt(IV))-backbone polymers (PPt) and the siRNA targeting polo-like kinase 1 (Plk1) are loaded on the surface of polyethyleneimine (PEI)-coated UCNPs (PUCNP) to obtain the multifunctional polyprodrug/siRNA loaded UCNPs (PUCNP@Pt@siPlk1). The PUCNP@Pt@siPlk1 can be served as a “nanotransducer” to convert NIR light (980 nm) into local ultraviolet (UV) to visible light for the cleavage of photosensitive PPt, resulting in the simultaneous on-demand release of high toxic platinum(II) (Pt(II)) and siPlk1. Meanwhile, the PUCNP@Pt@siPlk1 has CT, T 1 -weighted MR, and UCL tri-modality imaging abilities. Based on these merits, PUCNP@Pt@siPlk1 displayed excellent synergistic therapeutic efficacy via image-guided and NIR light-activated platinum-based chemotherapy and RNA interfering in vitro and in vivo. Thus, this developed nanosystem with NIR light-controlled drug/gene delivery and multi-modality imaging abilities, will display great potential in combining chemotherapy and gene therapy.
研究领域:
纳米技术
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癌症治疗
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药物递送系统
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医学成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2022
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IF 4.885
Shiying Zeng,Qinglai Tang,Kang Jiang,Xiaojun Tang
Metformin (MET) and survivin siRNA were delivered using silk fibroin nanoparticles (SFNs) modified with polyethyleneimine (PEI). Nanoparticle functional groups, structural, stability and physicochemical characteristics of the nanoparticles were determined. SFNs loaded with siRNA that had appropriate size, zeta potential , and stability were confirmed by various analytical and spectroscopical methods. The vitro cytotoxicity analysis was performed using CNE2 nasopharyngeal carcinoma cells with different compositions, and the results showed that the newly fabricated nanoparticles effectively triggered apoptosis in CNE2. Afterward, the mice analysis was used to investigate the in vivo therapeutic efficacy. With no apparent weight loss, the co-delivery systems dramatically slowed nasopharyngeal tumor development in mice. Survivin siRNA and MET increased the number of apoptotic tumor cells on histopathology slides. Apoptosis induction in cancer cells and therapeutic effectiveness were satisfactory with the drug delivery method. In this way, it might be used as a therapeutic agent in the fight against nasopharyngeal cancer.
研究领域:
医学
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药剂学
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肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
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2016
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IF 4.32
Ping Sun,Wei Huang,Mingji Jin,Qiming Wang,Bo Fan,Lin Kang,Zhonggao Gao
Nanoparticle-mediated small interfering RNA (siRNA) delivery is a promising therapeutic strategy in various cancers. However, it is difficult to deliver degradative siRNA to tumor tissue, and thus a safe and efficient vector for siRNA delivery is essential for cancer therapy. In this study, poly(ethylene glycol)-modified chitosan (PEG-CS) was synthesized successfully for delivering nucleic acid drug. We deemed that PEGylated CS could improve its solubility by forming a stable siRNA loaded in nanoparticles, and enhancing transfection efficiency of siRNA-loaded CS nanoparticles in cancer cell line. The research results showed that siRNA loaded in PEGylated CS (PEG-CS/siRNA) nanoparticles with smaller particle size had superior structural stability in the physical environment compared to CS nanoparticles. The data of in vitro antitumor activity revealed that 4T1 tumor cell growth was significantly inhibited and cellular uptake of PEG-CS/siRNA nanoparticles in 4T1 cells was dramatically enhanced compared to naked siRNA groups. The results from flow cytometry and confocal laser scanning microscopy showed that PEG-CS/siRNA nanoparticles were more easily taken up than naked siRNA. Importantly, PEG-CS/siRNA nanoparticles significantly reduced the growth of xenograft tumors of 4T1 cells in vivo. It has been demonstrated that the PEG-CS is a safe and efficient vector for siRNA delivery, and it can effectively reduce tumor growth and prevent metastasis.
研究领域:
癌症治疗
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药学
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纳米技术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cancer Nanotechnology
·
2023
·Vol. 14
·期 1
·1-34
·
IF 5.7
Tan Tiantian,Feng Yuxin,Wang Weimin,Wang Rongrong,Yin Liyan,Zeng Yiying,Zeng Zhaowu,Xie Tian
Background In the current treatment of non-small cell lung cancer (NSCLC), traditional chemotherapy causes high toxicity, so it is necessary to develop safe chemical drug delivery vehicles clinically. Chemotherapy monotherapy is prone to drug resistance. Chemotherapy combined with other therapies such as nucleic acid drugs is an effective way to avoid drug resistance and the toxicity of continuous chemotherapy. In this study, chemotherapy and siRNA therapy were combined to treat paclitaxel-resistant NSCLC in order to increase efficacy and reduce toxicity. This study aims to develop a cabazitaxel-loaded human serum albumin nanoparticles (CTX-HSA-NPs) to improve the toxicity of traditional CTX-Tween 80 and increase targeting, and to develop a TGFβ-1 siRNA lipid Nanoparticles (TGFβ-1 siRNA LNP) combined with chemotherapy in the treatment of paclitaxel-resistant NSCLC. Results This study prepared CTX-HSA-NPs and TGFβ-1 siRNA LNP had small particle size, high encapsulation efficiency (EE). CTX-HSA-NPs lyophilized powder has high stability after dissolved. The antitumor effect of CTX-HSA-NPs on paclitaxel-resistant NSCLC was higher than that of CTX-Tween, and the toxicity was 1.8 times lower than that of CTX-Tween. More importantly, the combined treatment of TGFβ-1 siRNA LNP and CTX-HSA-NPs could effectively improve the antitumor efficacy of paclitaxel-resistant NSCLC in vivo and in vitro. The results of tumor immunohistochemistry showed that TGFβ-1 siRNA LNP significantly inhibited the expression of TGFβ-1, and compared with other groups, the expression of P-gp after low-dose CTX-HSA-NPs treatment was lower, which did not cause obvious drug resistance. Conclusions The antitumor effect of CTX-HSA-NPs on paclitaxel-resistant NSCLC was higher than that of CTX-Tween, and the toxicity was lower than that of CTX-Tween. TGFβ-1 siRNA LNP can treat paclitaxel-resistant NSCLC by inhibiting the express of TGFβ-1 mRNA. The combined treatment of TGFβ-1 siRNA LNP and CTX-HSA-NPs could effectively improve the antitumor efficacy of paclitaxel-resistant NSCLC. A combination therapy of chemotherapy and nucleic acid drugs could be an effective approach for treating paclitaxel-resistant NSCLC.
研究领域:
肿瘤学
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药学
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分子生物学
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纳米技术
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Wenkai Zhang,Yi Jin,Jiayu Wang,Muge Gu,Yue Wang,Xiangqi Zhang,Yihui Zhang,Wei Yu,Yao Liu,Wei-En Yuan,Jing Su
Targeted elimination of damaged or overexpressed proteins within the tumor serves a pivotal role in regulating cellular function and restraining tumor cell growth. Researchers have been striving to identify safer and more effective methods for protein removal. Here, we propose the synergistic employment of a small molecule degrading agent (PROTAC) and siRNA to attain enhanced protein clearance efficiency and tumor therapeutic effects. Co-delivery liposomes were prepared to facilitate the efficient encapsulation of PROTAC and siRNA. Specifically, the cationic liposome significantly improved the solubility of the insoluble PROTAC (DT2216). The cationic polymer (F-PEI) achieved efficient encapsulation of the nucleic acid drug, thereby promoting endocytosis and enhancing the therapeutic impact of the drug. Both in vivo and in vitro experiments demonstrated remarkable degradation of target proteins and inhibition of tumor cells by the co-delivery system. In conclusion, the co-delivery liposomes furnished a nano-delivery system proficient in effectively encapsulating both hydrophilic and hydrophobic drugs, thereby presenting a novel strategy for targeted combination therapy in treating tumors.
研究领域:
药学
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癌症研究
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纳米技术
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分子生物学
✓ 已验证
DOI
高影响因子
BIOMATERIALS
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2015
·
IF 8.557
Tingjie Yin,Lei Wang,Lifang Yin,Jianping Zhou,Meirong Huo
In this study, a novel redox-sensitive micellar system constructed from a hyaluronic acid-based amphiphilic conjugate (HA-ss-(OA-g-bPEI), HSOP) was successfully developed for tumor-targeted co-delivery of paclitaxel (PTX) and AURKA specific siRNA (si-AURKA). HSOP exhibited excellent loading capacities for both PTX and siRNA with adjustable dosing ratios and desirable redox-sensitivity independently verified by morphological changes of micelles alongside in vitro release of both drugs in different reducing environments. Moreover, flow cytometry and confocal microscopy analysis confirmed that HSOP micelles were capable of simultaneously delivering PTX and siRNA into MDA-MB-231 breast cancer cells via HA-receptor mediated endocytosis followed by rapid transport of cargoes into the cytosol. Successful delivery and transport amplified the synergistic effects between the drugs while leading to substantially greater antitumor efficacy when compared with single drug-loaded micelles and non-sensitive co-loaded micelles. In vivo investigation demonstrated that HSOP micelles could effectively accumulate in tumor sites and possessed the greatest antitumor efficacy over non-sensitive co-delivery control and redox-sensitive single-drug controls. These findings indicated that redox-sensitive HSOP co-delivery system holds great promise for combined drug/gene treatment for targeted cancer therapy.
研究领域:
药剂学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
REACTIVE & FUNCTIONAL POLYMERS
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2021
·
IF 3.975
Yue Zhang,Lizhen Yu,Jun Zhu,Renmin Gong
In this paper, a novel grafted polymer (folate and carboxymethyl-β-cyclodextrin grafted trimethyl chitosan, FCT) was synthesized. Then the FCT nanoparticles (FCT NPs) were fabricated by ionic gelation and the potential of NPs as co-carrier of doxorubicin and siRNA was evaluated. The physicochemical properties of grafted polymer and NPs were characterized and analyzed by fourier transforms infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential and polydispersity index (PDI). The results showed the diameter of NPs ranged from 190 to 240 nm with polydispersity index of 0.192 and zeta potential of +21mv. The prepared NPs exhibited satisfactory drug loading capacity and encapsulation efficiency to doxorubicin and siRNA-survivin. Meanwhile, the prepared NPs could effectively protect siRNA-survivin from degradation of serum RNAase for a long time. Both drugs encapsulated in NPs all exhibited pH-dependent controlled sustained release characteristics and the cytotoxicity study testified that drug drug-loaded FCT NPs significantly improved the efficacy of antitumor drugs . The novel graft polymer was expected to become the co-carrier of anticancer and gene drugs in future with broad application prospects.
研究领域:
药剂学
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肿瘤学
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分子生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Mengjun Zhang,Huiyang Jiang,Lan Wu,Haoyu Lu,Hriday Bera,Xing Zhao,Xiong Guo,Xulu Liu,Dongmei Cun,Mingshi Yang
With specific and inherent mRNA cleaving activity, small interfering RNA (siRNA) has been deemed promising therapeutics to reduce the exacerbation rate of asthma by inhibiting the expression and release of proinflammatory cytokines from airway epithelial cells (AECs). To exert the therapeutic effects of siRNA drugs, nano-formulations with high efficiency and safety are required to deliver these nucleic acids to the target cells. Herein, we exploited novel inhaled lipid nanoparticles (LNPs) targeting intercellular adhesion molecule-1 (ICAM-1) receptors on the apical side of AECs. This delivery system is meant to enhance the specific delivery efficiency of siRNA in AECs to prevent the expression of proinflammatory cytokines in AECs and the concomitant symptoms in parallel. A cyclic peptide that resembles part of the capsid protein of rhinovirus and binds to ICAM-1 receptors was initially conjugated with cholesterol and subsequently assembled with ionizable cationic lipids to form the LNPs (Pep-LNPs) loaded with siRNA against thymic stromal lymphopoietin (TSLP siRNA). The obtained Pep-LNPs were subjected to thorough characterization and evaluations in vitro and in vivo . Pep-LNPs significantly enhanced cellular uptake and gene silencing efficiency in human epithelial cells expressing ICAM-1 in vitro , exhibited AEC-specific delivery and improved the gene silencing effect in ovalbumin-challenged asthmatic mice after pulmonary administration. More importantly, Pep-LNPs remarkably downregulated the expression of TSLP in AECs, effectively alleviated inflammatory cell infiltration , and reduced the secretion of other proinflammatory cytokines, including IL-4 and IL-13, as well as mucus production in asthmatic mice. This study demonstrates that Pep-LNPs are safe and efficient to deliver siRNA drugs to asthmatic AECs and could potentially alleviate allergic asthma by inhibiting the overexpression of proinflammatory cytokines in the airway.
研究领域:
药学
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纳米技术
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呼吸医学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2016
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IF 7.145
Lisi Xie,Yan Tan,Zhiyong Wang,Hong Liu,Na Zhang,Chao Zou,Xin Liu,Gang Liu,Jian Lu,Hairong Zheng
RNA interference (RNAi) therapy is a promising treatment for various diseases. However, its application is still restricted by the lack of efficient and safe delivery systems. A novel siRNA delivery vehicle based on ε-caprolactone-modified polyethylenimine (PEI-CL) is presented here. The PEI-CL macromolecules with different grafting degrees were synthesized via a simple ring-opening reaction. This macromolecule strongly protects the siRNA from degradation in serum and promotes the cellular uptake and endosomal escape detected via chemical exchange saturation transfer magnetic resonance analysis and fluorescence imaging. The in vivo measurement was performed with HCT-116 colon tumor xenograft that stably expressed luciferase. The data showed that the PEI-CL/siRNA nanocomplexes elicited strong RNAi response. More interestingly, enhanced gene transfection efficiency was achieved by simultaneous cotransfection with siRNA and DNA plasmid via this novel nanosystem. Overall, our study suggests the PEI-CL macromolecule with great promise for siRNA delivery.
研究领域:
药学
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生物技术
·
纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）