CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Yuanyuan Li,Pengcheng Feng,Cong Wang,Wenjun Miao,He Huang
The severe issues facing conventional therapies for triple negative breast cancer (TNBC), such as poor response rate and side effects, calls for new strategies to realize better prognosis. Owing to the merits of good efficacy, safety and facile implementation, phototherapy represents an attractive modality for this goal. Black phosphorus (BP) is a class of novel interesting materials for biomedical uses with advantages of biodegradability and optical activity. However, its stability, safety and biological performance remained to be further optimized. In this work, we report a novel light-responsive nanosystem, named [email protected] , for fluorescence imaging-guided synergistic photothermal and photodynamic therapy (PTT/PDT) against TNBC. Hyaluronic acid was coated onto NIR dye(cypate)-loaded BPN, resulting in favorable stability, excellent delivery efficiency into tumor cells and photothermal and photodynamic potential. Importantly, the safety profile of HBPN was greatly improved, compared to the counterpart without HA coating. Following NIR irradiation, localized generation of singlet oxygen and hyperthermia by [email protected] had a significant antitumor effect against both 4T1 cell monolayers and 3D organoids in vitro . Additionally, [email protected] showed significantly enhanced accumulation in tumor tissue and subsequently promoted light-triggered tumor ablation in a mouse model of TNBC. Taken together, this study demonstrates that novel nanophototherapeutics with great stability and safety profile such as [email protected] represent a promising platform for imaging-guided phototherapy for breast cancer treatment.
研究领域:
生物医学工程
·
癌症研究
·
纳米技术
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2021
·
IF 5.268
Xiao Kuang,Dongxu Chi,Jinbo Li,Chunlin Guo,Yinxian Yang,Shuang Zhou,Cong Luo,Hongzhuo Liu,Zhonggui He,Yongjun Wang
The platinum-based drugs prevail in the therapy of malignant tumors treatment. However, their clinical outcomes have been heavily restricted by severe systemic toxicities. To ensure biosafety and efficiency, herein, we constructed a disulfide bond inserted Pt(IV) self-assembled nanoplatform that is selectively activated by rich glutathione (GSH) in tumor site. Disulfide bond was introduced into the conjugates of oxaliplatin (IV) and oleic acid (OA) which conferred cascade reduction-responsiveness to nanoassemblies. Disulfide bond cleavage and reduction of Pt(IV) center occur sequentially as a cascade process. In comparison to oxaliplatin solution, Pt(IV) nanoparticles (NPs) achieved prolonged blood circulation and higher maximum tolerated doses. Furthermore, Oxa(IV)-SS-OA prodrug NPs exhibited potent anti-tumor efficiency against 4T1 cells and low toxicities in other normal tissues, which offers a promising nano-platform for potential clinical application.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDICINAL CHEMISTRY RESEARCH
·
2022
·Vol. 31
·期 4
·605-616
·
IF 2.351
Shi Jing-Fang,Wu Ping,Li Han-Xiang,Wei Xiao-Yi,Jiang Zi-Hua
Annonaceous acetogenins are potent ubiquinone-linked NADH oxidase inhibitors and have potent anticancer activity. Their usage in the clinic is limited because of their significant toxicity to normal cells. To obtain novel low toxicity antitumoral prodrugs, squamocin and bullatacin were covalently linked to N -butoxycarbonyl protected glycine-proline dipeptide (Boc-Gly-Pro), which may be recognized and cleaved by fibroblast activation protein (FAP), a serine protease overexpressed on the surface of tumor-associated fibroblasts. Ten squamocin and bullatacin derivatives were synthesized by attaching Boc-Gly-Pro either directly or through 6-aminocaproic acid linker to a hydroxyl group of squamocin or bullatacin. All derivatives showed high potency to inhibit 4T1 breast cancer cell line growth in the sub-µM to µM range. Compound 8 was the most active (IC 50 0.30 μM) and displayed higher activity than squamocin. Most derivatives, however, display reduced potency by up to 50 folds compared to the parent drug. In the presence of FAP enzyme, the anticancer potency of compound 3 against A549, HeLa, HepG2 and MCF-7 cells was increased by up to eight folds. The data suggest that Boc-Gly-Pro-acetogenin prodrugs may show improved therapeutic potential of these acetogenins by reducing the drug doses and the toxic side effects.
Graphical abstract
研究领域:
药理学
·
肿瘤学
·
药物化学
✓ 已验证
产品关联
DOI
高影响因子
Regenerative Biomaterials
·
2022
·
IF 5.763
He Ziyun,Wang Qiusheng,Zhang Nan,Yan Jianqin,Li Li,Cao Jun,He Bin
Combination therapy is extensively developed for cancer treatment in recent years due to its high efficiency. Herein, we constructed a nanocomposite based on gold nanorods (GNRs) and drug-loaded tetrahedral DNA nanostructures (TDN) for chemo-photothermal combinational therapy. Anti-tumor drug doxorubicin (DOX) was loaded via the insertion within GC base pairs of TDN. The aptamer AS1411 was attached to the apex of TDN (ATDN) to target tumor cells. The DOX-loaded DNA tetrahedron (ATDN-DOX) was compressed by the GNRs coated with PEI (GNRs@ATDN-DOX) to realize the photothermal function and lysosome escape. GNRs under the illumination of 808 nm infrared laser showed high photothermal conversion and stability due to the protection of PEI layer. The drug-loading capacity of ATDN-DOX was as high as 314 DOX molecules in per ATDN. The positive charge of PEI in GNRs@ATDN-DOX nanocomposites was utilized to achieve excellent cell penetration and induce proton sponge effect for lysosomal escape. The nanocomposites presented HeLa and 4T1 cells targeting and resulted in efficient anticancer activity.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2023
·
IF 15.1
Liang Xiao,Benjin Chen,Wanni Wang,Tian Tian,Haisheng Qian,Xiaohu Li,Yongqiang Yu
Radiotherapy (RT), a widely used clinical treatment modality for cancer, uses high-energy irradiation for reactive oxygen species (ROS) production and DNA damage. However, its therapeutic effect is primarily limited owing to insufficient DNA damage to tumors and harmful effects on normal tissues. Herein, a core-shell structure of metal–semiconductors (Au@AgBiS 2 nanoparticles) that can function as pyroptosis inducers to both kill cancer cells directly and trigger a robust anti-tumor immune against 4T1 triple-negative murine breast cancer and metastasis is rationally designed. Metal-semiconductor composites can enhance the generation of considerable ROS and simultaneously DNA damage for RT sensitization. Moreover, Au@AgBiS 2 , a pyroptosis inducer, induces caspase-3 protein activation, gasdermin E cleavage, and the release of damage-associated molecular patterns. In vivo studies in BALB/c mice reveal that Au@AgBiS 2 nanoparticles combined with RT exhibit remarkable antitumor immune activity, preventing tumor growth, and lung metastasis. Therefore, this core-shell structure is an alternative for designing highly effective radiosensitizers for radioimmunotherapy.
研究领域:
纳米技术
·
肿瘤学
·
免疫治疗
·
放射生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Chang Peng,Ming Zhao,Xuan Wang,Min Yan,Yanyan Han,Dawei Chen,Haiyang Hu
As an activator and alarm signal for tumor innate immune therapy, manganese ions can activate the stimulator of interferon genes (STING) pathway directly or indirectly. However, due to their high positive charge, manganese ions cannot freely penetrate biological membranes, and it is challenging to target their delivery into cells. Liposomes have been widely used as an effective drug delivery system. Using metal ions as active carriers to establish a gradient is an effective way to load chemotherapy drugs, but its low delivery efficiency and significant degradation of effective drugs by lysosomes may result in reduced therapeutic effects. In this study, we constructed an active drug-loading liposome ( [email protected] ) that enters cells through thiol-mediated endocytosis to encapsulate both the chemotherapy drug doxorubicin and manganese ions to achieve sustained manganese ion release. The combination of chemotherapy-induced immunogenic cell death and innate immune therapy with manganese ions was used to treat tumors. The liposome was able to reverse the immunosuppressive tumor microenvironment, reduce the resistance of B16F10 and 4T1 tumors to doxorubicin, and decrease the migration and invasion abilities of tumors by binding with lipoic acid.
研究领域:
癌症治疗
·
药物递送系统
·
免疫疗法
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2023
·Vol. 13
·期 9
·5609-5618
·
IF 3.9
Wen Kang,Yuyuan Shi,Zhenlu Yang,Xindao Yin,Ying Zhao,Lixing Weng,Zhaogang Teng
As a non-invasive cancer treatment, photodynamic therapy (PDT) has great applications in superficial tumors because of its high selectivity and low cumulative toxicity. However, the poor tumor-targeting ability and short blood circulation time of conventional photosensitizers (PSs) limit the efficacy of PDT to some extent. In this study, we synthesized flexible hollow human serum albumin (HHSA) and loaded photosensitizer Chlorin e6 (Ce6) and the chemotherapeutic drug Doxorubicin (DOX) for synergistic cancer therapy. HHSA can enhance drug delivery and cellular uptake through targeting gp60 and SPARC receptors and unique flexible hollow structures. The TEM images show that HHSA possesses distinct flexible hollow structures, as well as good monodispersity and deformability. After loading Ce6 and DOX, HHSA@Ce6-DOX displays better therapeutic effects than HHSA@DOX on the growth of 4T1 breast cancers without irradiation. Remarkably, it has a significantly higher therapeutic effect (relative cell activity: 45% vs. 74%) than HHSA@Ce6 under 660 nm irradiation. Furthermore, the excellent biocompatibility of HHSA@Ce6-DOX has been proved both in vitro and in vivo, indicating that it has a promising future in synergistic tumor treatments.
研究领域:
药学
·
纳米技术
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Xin Jin,Qiang Fu,Zehui Gu,Zhenhai Zhang,Huixia Lv
The stroma in solid tumors severely impedes drug delivery via systemic administration to cancer cells, especially when using nano-drug delivery systems. Therefore, we developed thermosensitive and in situ-formed hydrogels based on PLGA–PEG–PLGA, which delivered corilagin and low-molecular-weight chitosan (LC) directly to tumor cells via intratumor injection and promoted drug infiltration by modulating the tumor microenvironment . The hydrogels showed the desired thermosensitive properties and enabled corilagin to elicit its highest antitumor effect. Moreover, in 4T1 tumor-bearing mice, upon combination with the hydrogels, Abraxane® exhibited a better antitumor efficacy and increased paclitaxel accumulation in the tumor tissue by degradation of the tumor matrix caused by corilagin and the uptake-promoting effect of low-molecular-weight chitosan. These results suggest that the strategy of intratumor injection of hydrogels combined with systemic administration of drugs, especially nanotherapeutics, holds promise for enhanced treatment of malignant solid tumors.
研究领域:
药学
·
癌症研究
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2021
·
IF 6.988
Tingjie Yin,Xuxin Chu,Jiejie Cheng,Jinlai Liang,Jianping Zhou,Meirong Huo
A hypoxia-sensitive zwitterionic vehicle, DHigh-PEI-(A+P), with the ability for antifouling-mediated, stable biotransport and a photodynamic therapy (PDT)-sensitized hypoxic response for spatiotemporal controlled drug release, was developed for the tumor-specific delivery of chemotherapeutics and biomacromolecules. The amphiphilic DHigh-PEI-(A+P) was constructed from a betaine monomer (DMAAPS), a photosensitizer (PpIX), and an azobenzene-4,4′-dicarboxylic acid-modified polyethylenimine. Herein paclitaxel (PTX) was selected as a common model drug to verify the functions of the designed polymer. First, DHigh-PEI-(A+P) was demonstrated to spontaneously coassemble with PTX in aqueous solution with high drug loading (>35%). The desirable antifouling ability of DHigh-PEI-(A+P) was independently verified by efficient 4T1 endocytosis in serum alongside systemic tumor targeting. Furthermore, PpIX-mediated PDT was verified to aggravate and homogenize a hypoxic microenvironment at the cell and tissue levels for a sharp responsive disassembly of DHigh-PEI-(A+P) and thus a robust drug release in a well-controlled manner. As a result, DHigh-PEI-(A+P) amplified the therapeutic outcome of PTX on orthotopic 4T1 mouse models with minimal collateral damage. We proposed that DHigh-PEI-(A+P) may serve as a tailor-designed universal vehicle for the tumor-specific delivery of drugs with distinct physicochemical properties.
研究领域:
癌症治疗
·
药物递送系统
·
生物医学工程
·
纳米技术
·
药学科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Jiahui Yan,Haoyu Chen,Carlos F. Guimarães,Rui L. Reis,Zhihua Zhu,Tianyi Wang,Fenglan Zhang,Yaqian Lv,Qihui Zhou,Xiaoying Kong,Jinsheng Shi
Ion interference including copper (Cu + )/calcium (Ca 2+ ) overload activate cell-specific death channels, damage mitochondria and disrupt cellular homeostasis, showing great potential in anti-tumor therapy. However, the complex metabolic environment and the powerful self-protection of tumors cause clinical failure of ion interference. Thus, metabolic disruption is expected an innovative strategy for the enhancement of ion interference. Herein, CuS-α-CHCA&penthiopyrad@CaCO 3 -RGD nanoparticles (CCPCR NPs) are prepared to provide a Cu + /Ca 2+ dual-overload anti-tumor therapy assisted by metabolic-symbiosis-destruction strategy, realizing the collapse of tumor self-protection. Specifically, precise CuS and CaCO 3 delivery triggered irreversible Cu + /Ca 2+ dual-overload and reactive oxygen species (ROS) attack toward 4T1 cells. Meanwhile, α-CHCA and penthiopyrad disturbed the metabolic symbiotic environment by disrupting the TCA cycle and preventing lactate efflux to aggravate intracellular acidosis and promote Fenton-like reaction of Cu + , enhancing the sensitivity of tumor cells to copper death and Ca 2+ overload. Further, aided by the metabolism of symbiosis, the destroyed tumor cells further activate the polarization of M1 macrophages and the maturation and antigen cross-presentation of dendritic cells (DCs), which further eliminate tumor cells. In summary, an amplified anti-tumor dual-ion interference strategy assisted by metabolic symbiotic destruction is established, which is of great significance in improving the clinical effect of ion therapy for tumors.
研究领域:
肿瘤学
·
药学
·
免疫学
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2020
·Vol. 38
·期 8
·819-829
·
IF 3.154
Wang Ying-Sa,Li Gui-Liang,Zhu Shang-Bin,Jing Fan-Chen,Liu Run-Dong,Li Sai-Sai,He Jing,Lei Jian-Du
Oleanolic acid (OA) is a pentacyclic triterpenoid compound with extensive biological effects, such as anti-inflammatory and anticancer activities. However, the application of OA in chemotherapy is hampered by its poor solubility and severe adverse effects. To solve the problems, we developed a self-assembled nanoparticle platform based on amphiphilic oleanolic acid polyprodrug, poly[oligo(ethylene glycol) methyl ether methacrylate]- b -poly[oleanolic acid methacrylate] (POEGMA- b -POAMA), encapsulating 10-hydroxycamptothecin (HCPT) to achieve efficient cancer therapy. The polyprodrug was prepared via reversible addition-fragmentation chain transfer polymerization (RAFT), and could self-assemble to prepare POEGMA- b -POAMA/HCPT nanoparticles (NPs). The obtained nanoparticles exhibited appropriate particle size, excellent drug stability, good drug loading capacity, and high drug loading efficiency. In vitro drug release indicated that the drug release was prolonged to 132 h. The POEGMA- b -POAMA/HCPT NPs enhanced cell cytotoxicity in 4T1 cells and MCF-7 cells and could be efficiently uptaken by 4T1 cells. Furthermore, in vivo antitumor efficiency showed that the POEGMA -b -POAMA/HCPT NPs had great antitumor efficiency with considerably low adverse effects in the treatment of the 4T1 mouse breast tumor xenograft tumor. Therefore, POEGMA -b -POAMA/HCPT NPs provide great potential as a platform for drug delivery applications.
研究领域:
药学
·
纳米技术
·
癌症研究
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Hong Lu,Zhengyu Wu,Yijun Wang,Di Zhao,Biyun Zhang,Mei Hong
Background Triple-negative breast carcinomas (TNBCs) are a breast carcinoma with the most aggressive form, which is demonstrated as enhanced invasion and recurrence. Britannin is extracted mainly from the traditional Chinese herb Inula japonica Thunb, and few studies have focused on its effect on TNBC. Moreover, there is still no report concerning the role of Britannin in degrading the transcripts of Zinc finger E-box-binding homeobox 1 (ZEB1) proteins. Purpose To explore the potential effect of Britannin on invasion and stemness of TNBCs and its underlying mechanism. Methods Cellular activity was measured using MTT, and cell cycle was measured using flow cytometry (FCM). The effect of Britannin on the migrating and invading abilities of MDA-MB-231 and 4T1 cells were measured using the wound healing and transwell assays. The sizes and number of breast carcinoma cells were measured by tumor formation assay and in vitro limiting-dilution assay. CD44 expression in tumor spheroids was tested by immunofluorescence assay . Nextly, the expressions of epithelial-mesenchymal transition (EMT) markers and ZEB1 protein expressional level were detected by western blot . ZEB1 mRNA expressional level was analyzed using RT-qPCR. Drug affinity-responsive target stability (DARTS) method was used to detect the binding activity between Britannin and ZEB1. Co-immunoprecipitation (Co-IP) analysis was applied to test the ubiquitination of ZEB1. The mouse models for experimental lung metastasis of 4T1 cells were established to detect the anti-metastasis effect of Britannin in vivo , and the expressional levels of EMT markers in lung metastases were detected by immunohistochemistry . Results Britannin could inhibit cell growth and G2/M arrest in TNBC cells. Britannin could inhibit the migrating and invading ability without inducing severe apoptosis of MDA-MB-231 and 4T1 cells. Meanwhile, Britannin reduced the size and number of spheroids formed in these two cells, and decreased the expressional level of stem cells biomarker CD44 in tumor spheroids. Mechanism research showed that Britannin specifically bound to ZEB1 and induced its ubiquitination in MDA-MB-231 cells. Afterwards, Britannin disturbed protein stability and promoted ZEB1 protein degradation. Importantly, Britannin could not inhibit cell invasion and spheroid formation after ZEB1 expression was knocked down. Finally, Britannin inhibition of 4T1 cell metastasis was confirmed through establishing mouse models for the experimental lung metastasis. It was proved that both Britannin and paclitaxel could decrease the lung metastases, and Britannin could also down-regulate the protein expressional levels of ZEB1, MMP9 and CD44. Conclusion This study reveals that Britannin suppresses the invasion and metastasis of TNBC cells through degrading ZEB1, which suggests that Britannin can be used to prevent tumor metastasis and recurrence via degrading ZEB1proteins.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
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）