ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Lili Qian,Qian Li,Zhenshan Ding,Kejun Luo,Jiamin Su,Jiawei Chen,Guangying Zhu,Zhihua Gan,Qingsong Yu
Clinical radiation therapy (RT) is often hindered by the low radiation energy absorption coefficient and the hypoxic features of tumor tissues. Among the tremendous efforts devoted to overcoming the barriers to efficient RT, the application of hypoxic radiosensitizers and cell-cycle-specific chemotherapeutics has shown great potential. However, their effectiveness is often compromised by their limited bioavailability, especially in the hypoxic region, which plays a major role in radioresistance. Herein, to simultaneously improve the delivery efficacy of both hypoxic radiosensitizer and cell-cycle-specific drug, a gambogic acid (GA) metronidazole (MN) prodrug (GM) was designed and synthesized based on GA, a naturally occurring chemotherapeutic and multiple pathway inhibitor, and MN, a typical hypoxic radiosensitizer. In combination with MN-containing block copolymers, the prodrug nanosensitizer (NS) of GM was obtained. Owing to the bioreduction of MN, the as-designed prodrug could be efficiently delivered to hypoxic cells and act on mitochondria to cause the accumulation of reactive oxygen species. The strong G2/M phase arrest caused by the prodrug NS could further sensitize treated cells to external radiation under hypoxic conditions by increasing DNA damage and delaying DNA repair. After coadministration of the NS with a well-established tissue-penetrating peptide, efficient tumor accumulation, deep tumor penetration, and highly potent chemoradiotherapy could be achieved.
研究领域:
肿瘤学
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放射生物学
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药学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Polymers
·
2017
·Vol. 9
·期 4
·135
·
IF 3.364
Wenxia Cheng,Fengfeng Fan,Ying Zhang,Zhichao Pei,Wenji Wang,Yuxin Pei
By taking advantage of the self-polymerization of dopamine on the surface of magnetic nanospheres in weak alkaline Tris-HCl buffer solution, a facile approach was established to fabricate core-shell magnetic molecularly imprinted nanospheres towards hypericin (Fe3O4@PDA/Hyp NSs), via a surface molecular imprinting technique. The Fe3O4@PDA/Hyp NSs were characterized by FTIR, TEM, DLS, and BET methods, respectively. The reaction conditions for adsorption capacity and selectivity towards hypericin were optimized, and the Fe3O4@PDA/Hyp NSs synthesized under the optimized conditions showed a high adsorption capacity (Q= 18.28 mg/g) towards hypericin. The selectivity factors of Fe3O4@PDA/Hyp NSs were about 1.92 and 3.55 towards protohypericin and emodin, respectively. In addition, the approach established in this work showed good reproducibility for fabrication of Fe3O4@PDA/Hyp.Keywords:surface molecular imprinting;hypericin;magnetic nanospheres;dopamine;core-shell
研究领域:
材料科学
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药物化学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2025
·
IF 6
Xin Zhang,Li Li,Haiqing Niu,Zixin Liang,Liuqi Sang,Ning Wang,Fengli Huang,Xingzhi Han,Zhihao Liu,Xiao Shi,Qun Zhang,Jing Hu,Xiaoping Qian
Background The prognosis of patients with colorectal liver metastasis (CRLM) is poor. The 5-year survival rate of those who cannot be treated by surgery is less than 5 %, thus, the management of patients with CRLM remains a significant challenge. Based on the anti-tumor activity of traditional Chinese medicine monomer and the local immune activation caused by low dose radiotherapy combined with immune checkpoint inhibitors, we jointly applied it to explore the tumor inhibitory effect and the change of local immune microenvironment in liver metastasis model. Methods We engineered biomimetic nanoparticles through macrophage membrane encapsulation of gambogic acid (GA)-loaded PLGA cores, employing a double emulsion-solvent evaporation method to fabricate M-PLGA@GA nanoparticles. In tumor-bearing mice with surgically induced colorectal liver metastasis via hemisplenectomy, therapeutic efficacy was evaluated through intratumoral administration of M-PLGA@GA combined with triple-modality therapy: low-dose radiotherapy (LDRT; 5 Gy), anti-programmed cell death protein 1 monoclonal antibody (anti-PD-1 mAb; 200 μg), and nanoparticle delivery. This combinatorial approach leveraged spatial-temporal control of tumor microenvironment modulation. Results The nanoparticles augmented the targeted delivery ability of drugs to tumor cells and in vivo circulation duration, coupled with improved aqueous solubility of the encapsulated therapeutic agent, all while preserving its therapeutic potency. The radiotherapy notably augments the population of Dendritic cells (DCs) and bolsters the presentation of antigens to the tumor cells. Moreover, the administration of GA induces modifications in the tumor's immune microenvironment and escalates the fraction of CD8+ T cells. Within the context of the mouse CRLM model, the amalgamation of M-PLGA@GA with low-dose radiotherapy and immunotherapy markedly attenuates the pace of tumor proliferation and extends the survival of mice. Conclusions Our findings propose that a novel therapeutic regimen combining radiotherapy, immunotherapy, and Nanoparticle gambogic acid can effectively impede tumor progression in the mouse model of CRLM. Therefore, our study provides novel insights into the role of combined antitumor therapy on innate and adaptive antitumor immunity modulation for CRLM.
研究领域:
肿瘤学
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纳米医学
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放射治疗学
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免疫学
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药理学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Xiongqin Wang,Kunhui Sun,Junlin Dong,Yanli Ge,Haifan Liu,Xingyue Jin,Xiao Pei,Ping Wang,Jianbing Jiang,Tiejie Wang,Xuelei Hu,Shuguang Yuan,Bing Wang,Xie-an Yu
Carrier-free nanoparticles have attracted significant interest owing to their exceptional drug-loading efficiency, simple preparation, and good biosafety. Inspired by the synergism and attenuation strategy of natural products, carrier-free nanoparticles were constructed from a compatibility perspective, aiming to carry natural products to tumor sites as nanoparticles to achieve precise anti-cancer effects. Herein, the carrier-free nanoparticles based on gambogic acid and glycyrrhizic acid (GG NPs) were successfully formed via self-assembly. The internally generated "synergism and attenuation" GG NPs could enhance the anti-tumor effect, reduce toxicity to normal cells, and exhibit tumor-targeting capabilities. Further, to explore the role of GG NPs in enhancing phototherapy, the photosensitizer ZnPc 2 was self-assembled with GG NPs to form GGZ NPs. In vitro studies demonstrated that the GGZ NPs significantly improved phototherapecutic efficacy. Compared with ZnPc 2, the photothermal conversion efficiency was increased to 80.8 %, along with a 1.8-fold increase in tumor growth inhibition, and the singlet oxygen yield of GGZ NPs increased by 2-fold. In vivo experiments demonstrated that GGZ NPs exhibit significant liver-targeting ability and could reduce the liver toxicity induced by gambogic acid, as well as decrease the blood biochemical levels of AST and ALT, achieving externally assisted "synergism and attenuation". Hence, carrier-free nanoparticles based on natural products would bring a new treatment modality to the field of precision liver tumor therapy.
研究领域:
纳米技术
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癌症治疗
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光疗
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药学科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Dandan Mi,Jiaojiao Li,Rujing Wang,Yuke Li,Lan Zou,Chen Sun,Shenao Yan,Huan Yang,Mengnan Zhao,Sanjun Shi
Surgical removal remains the predominant treatment strategy for triple-negative breast cancer (TNBC). However, risks that include high locoregional recurrence and remote metastasis threaten patient survival and quality of life after surgery. In this study, a hydrogel based on poly (ethylene glycol) dimethacrylate and sericin methacryloyl was fabricated by photopolymerization to fill the resection cavity and prevent recurrence. The obtained hydrogel exhibited mechanical properties compatible with breast tissue and facilitated postsurgical wound management by promoting tissue regeneration. The DNA methylation inhibitor decitabine (DEC) and poly (lactic- co -glycolic acid)-encapsulated phytochemical gambogic acid (GA) were loaded into the hydrogel. The as-prepared hydrogel promoted fast release of DEC and sustained release of GA, leading to gasdermin E -mediated tumor cell pyroptosis and activating antitumor immune responses. Inducing postsurgical tumor cell pyroptosis inhibited local tumor recurrence and lung metastasis . While the dual-drug-loaded hydrogel system cured less than half of tumor-bearing mice, the cured mice survived for over half a year. These findings indicate that our hydrogel system is an excellent biocompatible platform for postsurgical TNBC therapy.
研究领域:
肿瘤学
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材料科学
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生物医学工程
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药理学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2022
·
IF 16.744
Yuhan Wang,Chunyan Yue,Mengyao Zhang,Dazhao Li,Tao Xu,Mengying He,Mengyuan Wang,Yanan Zhao,Zihui Ni,Feng Zhi,Yiqiao Hu,Dawei Ding
Combining chemotherapy and phototherapy (including photodynamic therapy and photothermal therapy) via nanoscale drug delivery systems has been widely explored to improve the therapeutic efficacy of cancers. Nevertheless, deficient reactive oxygen species (ROS) level caused by the excessive antioxidants (e.g., glutathione (GSH)) in tumor cells and thermoresistance mediated by heat shock proteins (HSPs) represent two pivotal obstacles for phototherapy. In addition, limited control on drug release via conventional nanocarriers results in unpredictable side effects of chemotherapeutic drugs. To tackle these problems, a novel phase change material (PCM)-based nanoplatform co-delivering paclitaxel (PTX), IR780 and gambogic acid (GA) was developed via a facile method to achieve chemotherapy synergized by dually-enhanced phototherapy of breast cancers. PCM-based nanoparticles (NPs) revealed favorable particle size and greatly improved photostability of IR780. PCM endowed the NPs with hyperthemia-triggered release of PTX for chemotherapy, which was beneficial to dampen the side effects. Upon the cellular uptake, GA-depleted intracellular GSH and blocked the overexpression of HSP90, which in turn simultaneously increased the ROS level and suppressed thermoresistance to enhance the efficacies of PDT and PTT, respectively. Finally, the dually-energized phototherapy and PTT-activated low-dose PTX-based chemotherapy achieved outstanding antitumor performances in vitro and in vivo. Taken together, via the NIR-activatable PCM-based NPs, a strategy of harnessing a single enhancer to boost the efficacies of dual-modal phototherapy and low-dose chemotherapy has been established for improved cancer treatment and reduced side effects.
研究领域:
癌症治疗
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纳米技术
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2024
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IF 10
Ruyi Wang,Yuxiao Xiao,Zhongtao Zhang,Xiaoxian Huang,Wanfang Zhu,Xiao Ma,Feng Feng,Wenyuan Liu,Lingfei Han,Wei Qu
Poor in vivo characteristics of gambogic acid (GA) and difficulties in industrial manufacturing of its nanocarriers have hindered its clinical translation. Therefore, a reproducible nano-drug delivery system must be developed to realize simpler manufacture and address inherent defects of GA, such as short circulation and severe side effects, in order to facilitate its clinical application. Herein, a drug self-assembled nanoparticles (NPs) consisting of a hydrophobic prodrug based on GA and oleyl alcohol (OA), as well as vitamin E-polyethylene glycol succinate (TPGS) as a shield to improve the stability of the NPs is reported. The preparation method is simple enough to stably facilitate large-scale manufacturing. The self-assembled NPs exhibit a remarkably high drug-loading capacity, and their prolonged circulation enables the NPs to demonstrate superior antitumor efficacy in both cellular and animal models. The flexible hydrophobic long chain wraps GA groups, which mitigates vascular irritation and reduces hemolysis rates. Consequently, the prodrug nano-system addresses GA-related concerns regarding stability, efficacy, and safety, offering a simple, stable, and secure nano-platform for similar candidate drugs.
研究领域:
药学
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纳米技术
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癌症研究
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药物开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2018
·
IF 4.556
Ye Yang,Hanxu Cai,Xiuyan Yuan,Huihui Xu,Yingying Hu,Xue Rui,Jingjing Wu,Jing Chen,Jing Li,Xiangdong Gao,Dengke Yin
Lung cancer is a kind of malignant tumor with high morbidity and metastasis tendency. Gambogic acid (GA) has demonstrated significant antitumor activity in vitro, but its poor water-solubility and adverse effects restrict its application in vivo and in clinic. In this study, a passive-targeting GA delivery system was prepared for orthotopic Lewis lung carcinoma model mice. Besides the ∼7 μm size distribution, slow and steady in vitro drug release in a week, high targeting effect to lung, effective restoration of histomorphological abnormalities in lung, maintaining on bodyweight, and prolongation on survival time, excellent improvements of the GA-loaded particles on physiological and psychological statuses and obvious inhibition on tumor metastasis to liver have also been observed, through the measurements of Porsolt forced swim, hypoxic tolerance time, ultrastructure of pulmonary capillary, pulmonary vascular permeability, and hepatic histological change. These results suggest that this GA-loaded particle may be an ideal approach to achieve satisfactory therapeutic function on lung cancer.
研究领域:
药理学
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肿瘤学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-13
·
IF 10.435
Zhang Gutian,Cheng Wenting,Du Lin,Xu Chuanjun,Li Jinlong
Background Phototherapy is a promising strategy for cancer therapy by reactive oxygen species (ROS) of photodynamic therapy (PDT) and hyperthermia of photothermal therapy (PTT). However, the therapeutic efficacy was restricted by tumor hypoxia and thermal resistance of increased expression of heat shock protein (Hsp). In this study, we developed albumin nanoparticles to combine hypoxia relief and heat shock protein inhibition to overcome these limitations for phototherapy enhancement. Results Near-infrared photosensitizer (IR780) and gambogic acid (GA, Hsp90 inhibitor) were encapsulated into albumin nanoparticles via hydrophobic interaction, which was further deposited MnO 2 on the surface to form IGM nanoparticles. Both in vitro and in vivo studies demonstrated that IGM could catalyze overexpress of hydrogen peroxide to relive hypoxic tumor microenvironment. With near infrared irradiation, the ROS generation was significantly increase for PDT enhancement. In addition, the release of GA was promoted by irradiation to bind with Hsp90, which could reduce cell tolerance to heat for PTT enhancement. As a result, IGM could achieve better antitumor efficacy with enhanced PDT and PTT. Conclusion This study develops a facile approach to co-deliver IR780 and GA with self-assembled albumin nanoparticles, which could relive hypoxia and suppress Hsp for clinical application of cancer phototherapy.
研究领域:
癌症治疗
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纳米技术
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光疗
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-22
·
IF 9.429
Li Rong-Tian,Zhu Yi-Dan,Li Wen-Ya,Hou Ying-Ke,Zou Yi-Ming,Zhao Ying-Hua,Zou Quan,Zhang Wen-Hua,Chen Jin-Xiang
A multifunctional nanoplatform with core–shell structure was constructed in one-pot for the synergistic photothermal, photodynamic, and chemotherapy against breast cancer. In the presence of gambogic acid (GA) as the heat-shock protein 90 (HSP90) inhibitor and the gold nanostars (AuNS) as the photothermal reagent, the assembly of Zr4+ with tetrakis (4-carboxyphenyl) porphyrin (TCPP) gave rise to the nanocomposite AuNS@ZrTCPP-GA (AZG), which in turn, further coated with PEGylated liposome (LP) to enhance the stability and biocompatibility, and consequently the antitumor effect of the particle. Upon cellular uptake, the nanoscale metal − organic framework (NMOF) of ZrTCPP in the resulted AuNS@ZrTCPP-GA@LP (AZGL) could be slowly degraded in the weak acidic tumor microenvironment to release AuNS, Zr4+, TCPP, and GA to exert the synergistic treatment of tumors via the combination of AuNS-mediated mild photothermal therapy (PTT) and TCPP-mediated photodynamic therapy (PDT). The introduction of GA serves to reduce the thermal resistance of the cell to re-sensitize PTT and the constructed nanoplatform demonstrated remarkable anti-tumor activity in vitro and in vivo. Our work highlights a facile strategy to prepare a pH-dissociable nanoplatform for the effective synergistic treatment of breast cancer.Graphical Abstract
研究领域:
癌症研究
·
纳米技术
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Wang Feng,Dong Lei,Wei Xixi,Wang Yongling,Chang Liansheng,Wu Hongwei,Liu Shuyuan,Chang Yuqiao,Yin Yaling,Luo Xiaoqiu,Jia Xiaojian,Yan Fei,Li Nana
Gambogic acid (GA) is a highly effective antitumor agent, and it is used for the treatment of a wide range of cancers. It is challenging to deliver drugs to the central nervous system due to the inability of GA to cross the blood–brain barrier (BBB). Studies have shown that ultrasound-targeted microbubble destruction can be used for transient and reversible BBB disruption, significantly facilitating intracerebral drug delivery. We first prepared GA–loaded porous-lipid microbubbles (GA porous-lipid/PLGA MBs), and an in vitro BBB model was established. The cell viability was detected by CCK-8 assay and flow cytometry. The results indicate that U251 human glioma cells were killed by focused ultrasound (FUS) combined with GA/PLGA microbubbles. FUS combined with GA/PLGA microbubbles was capable of locally and transiently enhancing the permeability of BBB under certain conditions. This conformational change allows the release of GA to extracellular space. This study provides novel targets for the treatment of glioma.
研究领域:
药理学
·
肿瘤学
·
神经科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2020
·Vol. 17
·期 9
·e2000066
·
IF 2.039
Zhiguo Mang,Shuai Zhang,Jing Bai,Meijuan Li,Hao Li
Structural simplification and modification of natural products are always very important resources to antitumor drugs. By introducing various aminomethyl groups and amide groups into the phenanthrene ring of tylophorine, a novel series of tylophorine derivatives have been designed and synthesized, and their antiproliferative activities against MCF-7, A549 and HepG-2 cells have been evaluated, too. The results indicated that most of the prepared compounds exhibited good antitumor activities. Especially, one compound with an {ethyl[2-(morpholin-4-yl)ethyl]amino}methyl group at the side chain exhibited the most significant cytotoxic effects.
研究领域:
肿瘤学
·
药物化学
·
天然产物研究
✓ 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）