Journal of Advanced Research
·
2024
·
IF 11.4
Zeliang Wu,Yuxiang Tang,Yuanhui Liu,Zhaozhao Chen,Yuao Feng,Hang Hu,Hui Liu,Gang Chen,Youming Lu,Yu Hu,Rong Xu
Introduction Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer with an extremely dismal prognosis and few treatment options. As a desmoplastic tumor, TNBC tumor cells are girdled by stroma composed of cancer-associated fibroblasts (CAFs) and their secreted stromal components. The rapidly proliferating tumor cells, together with the tumor stroma, exert additional solid tissue pressure on tumor vasculature and surrounding tissues, severely obstructing therapeutic agent from deep intratumoral penetration, and resulting in tumor metastasis and treatment resistance. Objectives Fucoxanthin (FX), a xanthophyll carotenoid abundant in marine algae, has attracted widespread attention as a promising alternative candidate for tumor prevention and treatment. Twist is a pivotal regulator of epithelial to mesenchymal transition, and its depletion has proven to sensitize antitumor drugs, inhibit metastasis, reduce CAFs activation and the following interstitial deposition, and increase tumor perfusion. The nanodrug delivery system co-encapsulating FX and nucleic acid drug Twist siRNA (siTwist) was expected to form a potent anti-TNBC therapeutic cyclical feedback loop. Methods and results Herein, our studies constituted a novel self-assembled polymer nanomedicine (siTwist/FX@HES-CH) based on the amino-modified hydroxyethyl starch (HES-NH 2 ) grafted with hydrophobic segment cholesterol (CH). The MTT assay, flow cytometry apoptosis analysis, transwell assay, western blot, and 3D multicellular tumor spheroids growth inhibition assay all showed that siTwist/FX@HES-CH could kill tumor cells and inhibit their metastasis in a synergistic manner. The in vivo anti-TNBC efficacy was demonstrated that siTwist/FX@HES-CH remodeled tumor microenvironment, facilitated interstitial barrier crossing, killed tumor cells synergistically, drastically reduced TNBC orthotopic tumor burden and inhibited lung metastasis. Conclusion Systematic studies revealed that this dual-functional nanomedicine that targets both tumor cells and tumor microenvironment significantly alleviates TNBC orthotopic tumor burden and inhibits lung metastasis, establishing a new paradigm for TNBC therapy.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
·
2016
·Vol. 105
·期 5
·1114-1125
·
IF 2.881
Shu-Di Yang,Wen-Jing Zhu,Qiao-Ling Zhu,Wei-Liang Chen,Zhao-Xiang Ren,Fang Li,Zhi-Qiang Yuan,Ji-Zhao Li,Yang Liu,Xiao-Feng Zhou,Chun Liu,Xue-Nong Zhang
The development of effective and stable carriers of small interfering RNA (siRNA) is important for treating cancer with multidrug resistance (MDR). We developed a new gene and drug co-delivery system and checked its characteristics. Low-density lipoprotein (LDL) was coupled with N-succinyl chitosan (NSC) Lipoic acid (LA) micelles and co-delivered MDR1 siRNA and paclitaxel (PTX-siRNA/LDL-NSC-LA) to enhance antitumor effects by silencing the MDR gene of tumors (Li et al., Adv Mater 2014;26:8217-8224). In our study, we developed a new type of containing paclitaxel-loaded micelles and siRNA-loaded LDL nanoparticle. This “binary polymer” is pH and reduction dual-sensitive core-crosslinked micelles. PTX-siRNA/LDL-NSC-LA had an average particle size of (171.6 ± 6.42) nm, entrapment efficiency of (93.92 ± 1.06) %, and drug-loading amount of (12.35% ± 0.87) %. In vitro, MCF-7 cells, high expressed LDL receptor, were more sensitive to this delivery system than to taxol ® and cell activity was inhibited significantly. Fluorescence microscopy showed that PTX-siRNA/LDL-NSC-LA was uptaken very conveniently and played a key role in antitumor activity. PTX-siRNA/LDL-NSC-LA protected the siRNA from degradation by macrophage phagocytosis and evidently down-regulated the level of mdr1 mRNA as well as the expression of P-gp. We tested the target ability of PTX-siRNA/LDL-NSC-LA in vivo in tumor-bearing nude mice. Results showed that this system could directly deliver siRNA and PTX to cancer cells. Thus, new co-delivering siRNA and antitumor drugs should be explored for solving MDR in cancer. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1114–1125, 2017.
研究领域:
药学
·
生物医学工程
·
肿瘤学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2016
·Vol. 10
·期 2
·690-703
·
IF 8.893
Ding Jie,Liang Tingxizi,Zhou Ying,He Zhiwei,Min Qianhao,Jiang Liping,Zhu Junjie
Drug resistance renders standard chemotherapy ineffective in the treatment of connective tissue growth factor (CTGF)-overexpressing breast cancer. By co-embedding the breast tumor cell-penetrating peptide (PEGA-pVEC) and hyaluronic acid (HA) as a targeting media, novel cascaded targeting nanoparticles (HACT NPs) were created on a rattle mesoporous silica (rmSiO 2 ) scaffold for the pinpoint delivery of siRNAs along with an anticancer drug, aiming at overcoming the drug resistance of CTGF-overexpressing breast cancer in vivo . The targeting nanoparticles selectively accumulated in the vasculature under the guidance of the PEGA-pVEC peptide, cascaded by receptor-mediated endocytosis with the aid of another targeting agent, HA, presenting a greater in vivo tumor targeting ability than single targeting ligand vectors. In addition, an HA shell prevented the leakage of therapeutic drugs during the cargo transport process, until the hyaluronidase (HAase)-triggered degradation upon lysosomes entering, guaranteeing a controllable drug release inside the target cells. When the protective shell disintegrates, the released siRNA took charge to silence the gene associated with drug resistance, CTGF, thus facilitating doxorubicin-induced apoptosis. The cascaded targeting media (PEGA-pVEC and HA) advances precision-guided therapy in vivo , while the encapsulation of siRNAs into a chemotherapy drug delivery system provides an efficient strategy for the treatment of drug resistance cancers.
研究领域:
纳米技术
·
癌症研究
·
药学
·
分子生物学
·
生物医学工程
✓ 已验证
DOI
高影响因子
Polymer Chemistry
·
2015
·Vol. 6
·期 13
·2445-2456
·
IF 5.52
Minghui Xu,Junmin Qian,Aili Suo,Ting Liu,Xuefeng Liu,Hongjie Wang
To enhance the therapeutic efficacy of doxorubicin (DOX) to breast cancer cells, a multifunctional triblock copolymer, poly(ethylene glycol)-block-poly(L-glutamic acid γ-hydrazide)-block-polyethylenimine (PEG-b-PGAH-b-PEI) having a cleavable disulfide linkage between blocks, was developed as a vehicle for targeted co-delivery of DOX and P-glycoprotein (P-gp) siRNA into MCF-7/ADR cells. The PGAH blocks were used to chemically conjugate DOX molecules via hydrazone bonds, while the PEI blocks could complex siRNA through electrostatic interactions. A tumor-targeting agent, folic acid (FA), was attached to the distal ends of the PEG blocks to specifically bind to the folate receptors overexpressed in MCF-7/ADR cells. The DOX-conjugated copolymer would self-assemble in aqueous solutions into cationic nanomicelles, which could condense siRNA to form nanomicelleplexes with an average particle size of ∼194 nm and a positive zeta potential of >+10 mV. The nanomicelleplexes exhibited sustained drug release profiles, and the release rates of DOX and siRNA from the nanomicelleplexes in a reductive acidic environment (pH 5.0 + 10 mM glutathione) were much faster than those under physiological conditions (pH 7.4). FA-decorated nanomicelleplexes were more efficiently internalized by MCF-7/ADR cells via folate-receptor-mediated endocytosis and exhibited a higher cytotoxic effect on MCF-7/ADR cells in comparison with FA-undecorated nanomicelleplexes. Furthermore, the synergistic effects of DOX and P-gp siRNA in inhibiting cell proliferation and inducing apoptosis in MCF-7/ADR cells were achieved by the FA-targeted co-delivery system. The triblock copolymer itself had a low cytotoxicity. These results indicate that the triblock copolymer could serve as an ideal tumor-targeting vehicle for simultaneous delivery of drugs and siRNA in breast cancer therapy.
研究领域:
药学
·
纳米技术
·
癌症治疗
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Xiuna Jia,Mengmeng Lv,Yunwei Fei,Qing Dong,Hao Wang,Qiong Liu,Dan Li,Jin Wang,Erkang Wang
Diagnosis-guided synergistic treatment based on innovative nanomaterials is of great significance for the development of anti-cancer therapies. However, the low delivery efficiency of therapeutic gene and the inability to trigger release on demand are still major obstacles impeding its wide application. Herein, we report an ultra-fast one-step method within 2 min to prepare a smart carrier, liposome-coated Prussian blue @ gold nano-flower, which is named LPAR after linking with tumor-targeting peptide. The versatile LPAR not only can respond to near-infrared (NIR) light, achieve the selective delivery and the controlled release of siRNA targeting the mutant gene of Kras at its codon-12 from Glycine (G) to Aspartic acid (D) (named as G12D mutant gene) in the malignant pancreatic tumors, but also efficiently convert the absorbed NIR light into the heat to realize gene-photothermal synergistic therapy both in vitro and in vivo . Theoretical simulation results reveal that the outstanding photothermal conversion efficiency of LPAR is mainly due to its higher electric field intensity and power density distributions . Furthermore, the LPAR possesses the capabilities for triple-modal imaging. Therefore, the developed NIR light-responsive LPAR has the potential to be served as a tumor-targeted nano-delivery system for imaging-guided synergistic therapy of cancers.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
分子生物学
·
药学
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Ying Li,Xin Zhang,Dan He,Zhijie Ma,Ke Xue,Haiyan Li
Diabetic chronic wounds are difficult to heal because of the presence of excessive inflammation and high overexpression of matrix metalloproteinase-9 (MMP-9), which greatly affects the quality of life of patients with diabetes and increases the risk of death. Thus, the regulation of excessive inflammation and inhibition of MMP-9 overexpression are effective strategies to improve diabetic wound healing. The present study is the first to demonstrate that ion products of 45S5 Bioglass® (BG) can work with small interfering RNA of MMP9 (MMP9-siRNA) to reduce MMP-9 expression in tissue-forming cells and enhance the synthesis of extracellular matrix proteins (ECMs). Specifically, the BG ionic products can stimulate macrophages to convert to M2 phenotype, thereby creating a proregenerative inflammation microenvironment to indirectly suppress the expression of MMP-9 in tissue-forming cells. Chitosan nanoparticles encapsulating MMP9-siRNA (MMP9-siNP) can directly lower MMP-9 expression in tissue-forming cells. In addition, BG ionic products can promote the vascularization of endothelial cells and ECM protein synthesis by fibroblasts. Thus, injectable BG/sodium alginate (BG/SA) hydrogels loaded with MMP9-siNP can significantly accelerate the healing process of full-thickness excision wounds of diabetic rats by decreasing MMP-9 expression, improving collagen synthesis , and enhancing angiogenesis in the wounds, thereby demonstrating their great application potential in treating diabetic chronic wounds. Statement of significance Excessive inflammation and high overexpression of MMP-9 have been considered as factors that severely hinder the healing process of diabetic chronic wounds. Effective strategies are required for the regulation of excessive inflammation and inhibition of MMP-9 overexpression to enhance diabetic wound healing. In the present work, an injectable bioglass/sodium alginate (BG/SA) hydrogel loaded with MMP9-siNP was developed; this hydrogel significantly accelerated the healing process of full-thickness excision wounds of diabetic rats by decreasing MMP-9 expression, improving collagen accumulation, and enhancing angiogenesis in the wounds. Thus, the BG/SA hydrogel loaded with MMP9-siNP has great potential for use in healing of diabetic chronic wounds.
研究领域:
生物材料
·
伤口愈合
·
糖尿病
·
组织工程
·
纳米技术
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Qian Ren,Tingting Tian,Bin Wang,Jun Pan,Yong Huang,Li Zhong,Yehong Wang,Xia Wang,Xiao Huang
Photodynamic therapy (PDT) remains underutilized as a primary cancer treatment due to the limited lethality of reactive oxygen species (ROS) and poor targeting efficiency of traditional photosensitizers. This the aim of the study is to develop a Fe₃O₄@ZnO nanoparticle photosensitizer co-loaded with anti-EGFR antibody, brusatol, and Nrf2-siRNA to improve the therapeutic effect of PDT. This system can be guided to tumors by a magnetic field and further targets cancer cells through EGFR-specific binding. Under UVA light, brusatol and Nrf2-siRNA are released, enabling combined chemo-, gene, and photodynamic therapy. With the photosensitizer treatment, ROS levels in cutaneous squamous cell carcinoma cells were elevated by 191.09 ± 10.02 % through suppression of Nrf2 and its associated antioxidant defenses, significantly enhancing cell lethality and reducing cell viability by 80.43 ± 9.37 %. In vivo studies further demonstrated a tumor suppression rate of 76.30 ± 5.12 % in nude mice, highlighting the robust anti-tumor efficacy of the photosensitizer and its potential for clinical application in targeted cancer therapy. The biocompatibility and high therapeutic efficacy of this photosensitizer highlight its promise as a safer and more effective option for treating cutaneous squamous cell carcinoma.
研究领域:
癌症治疗
·
纳米技术
·
药理学
·
分子生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2021
·
IF 5.275
Jin-Yu Liu,Xu-Ying Liu,Rui Liu,Fang Tang,Jing-Bo Yang,Quan Tang,Zhong-Lin Lu,Hai-Jun Qiao,Lan He
Two-photon fluorescent Acenaphtho[1,2- b ]quinoxaline (ANQ) and the hydrophilic di-(triazole-[12]aneN 3 ) moieties were combined through an alkyl chain ( ANQ-A-M ) or a β -hairpin motif with two aromatic γ -amino acid residues ( ANQ-H-M ) to explore their capabilities for in vitro and in vivo gene delivery and tracing. ANQ-A-M and ANQ-H-M showed the same maximum absorption at 420 nm, and their fluorescent intensities around 650 nm were varied in different solvents and became poor in the protic solvents. Gel electrophoresis assays indicated that both compounds completely retarded the migration of pDNA at 20 μM in the presence of DOPE . However, the DNA condensation with ANQ-H-M was not reversible, and the particle size of the corresponding complexes were larger indicated from the SEM and DLS measurements. In vitro transfections indicated ANQ-A-M /DOPE achieved Luciferase and GFP expressions were to be 7.9- and 5.7-fold of those by Lipo2000 in A549 cells respectively. However, ANQ-H-M showed very poor transfection efficiency in Luciferase expression. With the help of single/two-photon fluorescence imaging it clearly demonstrated that the successful transfection of ANQ-A-M was attributed to its cellular uptake, apparent lysosomal escape, and reversible release of DNA; and the poor transfection of ANQ-H-M was resulted from the aggregation of the DNA complexes which prevented them from the cellular uptake, and also the strong binding ability which is not easy to release DNA. ANQ-A-M /DOPE also exhibited robust gene silencing (83% knockdown of Luciferase) and GFP expression (2.47-fold higher) efficiency compared with Lipo2000 in A549 and zebrafish, respectively. The work demonstrated that the linkage structure between fluorescent and di(triazole-[12]aneN 3 ) played the important role for their gene delivery performance, and that ANQ-A-M represents a vector with the strong transfection efficiency in vitro and in vivo as well as the efficient real time bioimaging properties, which is potential for the development in biomedical research.
研究领域:
生物医学工程
·
分子生物学
·
药学
·
生物化学
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2017
·
IF 7.786
Zhi-qiang Yuan,Wei-liang Chen,Ben-gang You,Yang Liu,Shu-di Yang,Ji-zhao Li,Wen-jing Zhu,Xiao-feng Zhou,Chun Liu,Xue-nong Zhang
Malignant proliferation and metastasis in non-small cell lung carcinoma (NSCLC) are great challenges for effective clinical treatment through conventional chemotherapy. The combinational therapy strategy of RNA interfering (RNAi) technology and chemotherapeutic agents have been reported to be promising for effective cancer therapy. In this study, based on multifunctional nanoparticles (NPs), the simultaneous delivery of etoposide (ETP) and anti-Enhancer of Zeste Homologue 2 (EZH2) siRNA for the effective treatment of orthotopic lung tumor was achieved. The NPs exhibited pH/redox dual sensitivity verified by particle size changes, morphological changes, and in vitro release of drugs. Confocal microscopy analysis confirmed that the NPs exhibited endosomal escape property and on-demand intracellular drug release behavior, which can protect siRNA from degradation and facilitate the chemotherapeutic effect respectively. In vitro tumor cell motility study demonstrated that EZH2 siRNA loaded in NPs can decrease the migration and invasion capabilities of tumor cells by downregulating the expression of EZH2 mRNA and protein. In particular, an antiproliferation study revealed that the co-delivery of siRNA and ETP in the multifunctional NPs can induce a synergistic therapeutic effect on NSCLC. In vivo targeting evaluation showed that cRGDyC-PEG modification on NPs exhibited a low distribution in normal organs and an obvious accumulation in orthotopic lung tumor. Furthermore, targeted NPs co-delivering siRNA and ETP showed superior inhibition on tumor growth and metastasis and produced minimal systemic toxicity. These findings indicated that multifunctional NPs can be utilized as a co-delivery system, and that the combination of EZH2 siRNA and ETP can effectively treat NSCLC.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2024
·
IF 10.7
Xianglei Fu,Yanbin Shi,Zili Gu,Hengchang Zang,Lian Li,Qingjie Wang,Yongjun Wang,Xiaogang Zhao,Hang Wu,Shengnan Qiu,Yankun Zhang,Jiamin Zhou,Xiangqin Chen,Hua Shen,Guimei Lin
Despite standard treatment for non-small cell lung cancer (NSCLC) being surgical resection, cancer recurrence and complications, such as induction of malignant pleural effusion (MPE) and significant postoperative pain, usually result in treatment failure. In this study, an alginate-based hybrid hydrogel (SOG) is developed that can be injected into the resection surface of the lungs during surgery. Briefly, endoplasmic reticulum-modified liposomes (MSLs) pre-loaded with the signal transducer and activator of transcription 3 (STAT3) small interfering RNA and lidocaine hydrochloride are encapsulated in SOG. Once applied, MSLs strongly downregulated STAT3 expression in the tumor microenvironment, resulting in the apoptosis of lung cancer cells and polarization of tumor-associated macrophages towards the M1-like phenotype. Meanwhile, the release of lidocaine hydrochloride (LID) was beneficial for pain relief and natural killer cell activation. Our data demonstrated MSL@LID@SOG not only efficiently inhibited tumor growth but also potently improved the quality of life, including reduced MPE volume and pain relief in orthotopic NSCLC mouse models, even with a single administration. MSL@LID@SOG shows potential for comprehensive clinical management upon tumor resection in NSCLC, and may alter the treatment paradigms for other cancers.
研究领域:
肿瘤学
·
药理学
·
生物医学工程
·
免疫疗法
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Yifu Lyu,Xiuyi Yang,Lei Yang,Jinyu Dai,Huanyu Qin,Yunuo Zhou,Yunan Huang,Yanmei Wang,Di Wu,Qindai Shuai,Qilong Li,Xiaofei Xin,Lifang Yin
Lipid nanoparticle-mediated co-delivery of siRNA and small molecule holds a great potential to treat metabolic dysfunction-associated steatotic liver disease (MASLD). However, targeted delivery of therapeutics to hepatocytes remains challenging. Taking the advantage of rising low density lipoprotein receptor/very-low density lipoprotein receptor (LDLR/VLDR) levels in MASLD, the biological fate of dinonylamine-ethylene glycol chlorophosphate-1-nonanol (DNNA-COP-NA) based lipid nanoparticles (LNPs) was oriented to liver tissues via apolipoprotein E (ApoE)-LDLR/VLDLR pathway. We then adopted a three-round screening strategy to optimize the formulation with both high potency and selectivity to deliver siRNA-HIF-1α (siHIF1α) and silibinin (SLB) payloads to hepatocytes. The optimized SLB/siHIF1α-LNPs mediates great siRNA delivery and transfection of hepatocytes. In high fat diet (HFD)- and carbon tetrachloride (CCl 4 )-induced mouse models of MASLD, SLB/siHIF1α-LNPs enabled the silencing of hypoxia inducible factor-1α (HIF-1α), a therapeutic target primarily expressed by hepatocytes, leading to significantly reduced inflammation and liver fibrosis synergized with SLB. Moreover, it is demonstrated the hepatocyte-targeting delivery of SLB/siHIF1α-LNPs has the potential to restore the immune homeostasis by modulating the population of Tregs and cytotoxic T cells in spleen. This proof-of-concept study enable siRNA and small molecule co-delivery to hepatocytes through intrinsic variation of targeting receptors for MASLD therapy.
研究领域:
药学
·
分子生物学
·
肝病学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHOTOCHEMISTRY AND PHOTOBIOLOGY
·
2018
·Vol. 95
·期 4
·1045-1051
·
IF 2.214
Xian Zhang,Longfei Chen,Lvfen Gao,Xuesong Gao,Nan Li,Yuwei Song,Xinke Huang,Shaoqiang Lin,Xiaoyu Wang
Comparison of the fluorescence intensity caused by the accumulation of PpIX in endometrial cancer xenografts in nude mice after low-dose 5-Aminolevulinic acid (ALA) injection combined with siRNA transfection was mediated by ultrasound microbubbles and polyethyleneimine (PEI) to explore the feasibility of the ultrasound microbubble technique as transfection agents. Knockdown of ferrochelatase (FECH) in human endometrial cancer xenografts in nude mice was performed by transfection with FECH-siRNA mediated by PEI and ultrasound microbubbles alone or in combination; then, low-dose ALA was injected. Subsequently, an in vivo animal imaging system was employed to detect the fluorescence intensity in xenografts. Red fluorescence was observed in xenografts given more than 6.25 mg kg −1 of ALA. When the dose of ALA was greater than 50 mg kg −1 , there was a significant difference in the fluorescence between tumor and other tissues. After the nude mice were transfected with siRNA and treated with low-dose ALA (1.0 mg kg −1 ), apparent PpIX fluorescence of the xenografts was observed, and the fluorescence intensity was PEI+ ultrasound microbubbles > PEI > ultrasound microbubbles. Ultrasound microbubbles in combination with PEI could generate a higher fluorescence intensity of PpIX than that obtained with ultrasound microbubbles or PEI alone, and ultrasound microbubbles could wholly or partially replace PEI under certain conditions.
研究领域:
肿瘤学
·
分子生物学
·
基因治疗
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）