Current Drug Delivery
·
2022
·Vol. 19
·期 4
·491-507
·
IF 3.758
Zhao Xinghua,Ding Shi,Li Shengnan,Wang Yang,Jiang Mingjun,Liu Ju,Chen Ye
Aim: An active-passive dual-targeting gambogic acid HPMA Copolymer Coupling drug system with high efficiency, low toxicity and high selectivity was constructed. Methods: The gambogic acid HPMA copolymer coupling drug system was constructed and its structure was characterized. The
cytotoxicity of gambogic acid HPMA copolymer was detected by MTT assay. The pharmacokinetics of gambogic acid HPMA copolymer was evaluated in mice. Targetability of gambogic acid HPMA copolymer was evaluated by tissue distribution experiment. The in vitro antitumor activity of gambogic acid
HPMA copolymer was evaluated by pharmacodynamics experiment in mice. Results: Two copolymers of gambogic acid HPMA were successfully prepared. The copolymers showed reduced cytotoxicity and a certain sustained release effect and targeting property. In vivo pharmacodynamic experiments
also showed better anti-tumor effects than GA. Discussion: In this study, gambogic acid was combined with HPMA polymer and the targeting molecule D-galactose/folic acid to form a polymer micelle with high efficiency, low toxicity and high selectivity for active-passive dual targeting.
The construction of the drug system provides new ideas for future formulation research and development.
研究领域:
药学
·
肿瘤学
·
生物医学工程
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Ding Zhang,Boqi Chen,Qingke Mu,Wei Wang,Kaili Liang,Liyan Wang,Qing Wang
Anti-cutaneous melanoma activity of the skin-delivered gambogic acid (GA) has been reported in our previous study. However, it is difficult for GA to diffuse passively through intact skin without any enhancement means. In this study, a combination of chemical enhancers (EN: azone and propylene glycol) and physical ultrasound (US) was used to improve the percutaneous permeation of GA and enhance the anti-melanoma activity. The enhancement effect of the combination of EN and US (EN-US) on GA in vitro and in vivo was studied, and the enhancement mechanism and skin irritation were also evaluated. We showed that the parameters of US application at a constant frequency (30 kHz) with a duty cycle of 100% and intensity of 1.75 W/cm 2 for 20 min were optimal. In vitro , EN-US showed a considerable enhancement of the permeation of GA, and the enhancement effect was stronger than that with the use of EN or US alone. In vivo antitumor study showed that the tumor growth was significantly inhibited after percutaneous administration of GA by EN-US, more than in the intravenous injection group. The penetration enhancement mechanism revealed that EN-US not only altered the structure of lipid bilayers and keratins to reduce the barrier effect of the stratum corneum but also produced diffusion channels in the skin under the cavitation effect of US, thereby promoting the skin penetration of GA. In addition, there was no observable skin irritation in mice after treatment with EN-US. Our study demonstrated that the combination of EN and US improved the skin permeation and retention of GA to enhance the anti-melanoma activity. This method also provides technical guidance for the future development of topical and transdermal therapeutic system of GA.
研究领域:
药理学
·
肿瘤学
·
皮肤病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2022
·
IF 6.633
Ziling Chang,Yuxiang Yang,Bo Zhao,Huafei Li,Yuxia Guan,Yi Zhao,Hongming Yuan,Chaoying Ni
Hydrophilic mesoporous organosilica nanoparticles (HMNPs) were synthesized by introducing Fe 3 O 4 on the basis of mesoporous organosilicon nanoparticle hollow spheres as a drug carrier. N- and S- doped graphene quantum dots (NS-GQDs) and polyethylenimine (PEI) were grafted onto the surface of HMNPs. Finally, two types of composite mesoporous particles, HMNPs-NS-GQDs-PEI-HA and HMNPs-NS-GQDs-PEI-FA which can enter VX2 cells for fluorescence confocal imaging, were further modified by targeting ligand hyaluronic acid (HA) and folic acid (FA). The heteroatoms of NS-GQDs have intelligent functional effects, which can not only improve the photoluminescence performance of GQDs, but also generate conjugated quantum dots with GA, so as to synergistically improve the drug effectiveness. Under illumination by near-infrared (NIR) radiation, gambogic acid (GA)-loaded HMNPs was promoted to the sustained release of gambogic acid. The loading and sustained release of the anticancer drug GA on the compound mesoporous particles were studied. The cytotoxicity and antitumor properties of the compound mesoporous particles were investigated by both in vitro cell experiments and in vivo experiments in mice. The results showed that HMNPs-NS-GQDs-PEI-HA and HMNPs-NS-GQDs-PEI-FA have desired fluorescence and magnetic properties for cell fluorescence imaging and magnetic targeting of cancer cells. Both of composite mesoporous particles have desired loading capacity on GA and pH-responsive drug release behavior as well as low cytotoxicity and good biocompatibility. The cell survival rate of HMNPs-NS-GQDs-PEI-HA and HMNPs-NS-GQDs-PEI-FA loaded with GA was only 7.69% and 8.71%, respectively, after 24 h, which can effectively induce the apoptosis of VX2 cells. Tumor experiments in mice demonstrated that HMNPs-NS-GQDs-PEI-HA inhibits tumor growth and exhibits magnetic targeting function.
研究领域:
材料科学与工程
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2020
·
IF 2.997
Ding Zhang,Wei Wang,Tao Hou,Yanjun Pang,Chao Wang,Shuai Wu,Qing Wang
Cutaneous melanoma is the deadliest form of skin cancer, and gambogic acid (GA) exhibits potent anti-melanoma activity. However, clinical application of GA via intravenous injection and oral administration is limited by systemic toxicity and rapid metabolism in the blood. Here, we developed a new, topical route of GA delivery for anti-melanoma activity and reduction of systemic toxicity. The results indicated that the barrier of the stratum corneum (SC) and low diffusion of GA in the hydrophilic viable skin (epidermis and dermis) limited the GA penetration through intact skin. The combination of azone (AZ) and propylene glycol (PG) showed obvious synergistic effects on skin penetration by GA via improving the permeability of the SC and greatly increasing the skin accumulation of GA, thereby forming a high drug concentration in the skin and achieving a topical targeted treatment of melanoma . In addition, GA (AZ–PG) achieved the same anti-melanoma effect via topical delivery as via intravenous injection. Intravenous injection and oral administration of GA induced remarkable pathological changes in various organs in mice, whereas GA was not toxic to various organs or to the skin via topical delivery. These findings indicated that topical administration of GA is an alternative route for melanoma treatment.
研究领域:
肿瘤学
·
药理学
·
皮肤病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ChemistrySelect
·
2024
·Vol. 9
·期 28
·e202401909
·
IF 1.9
Zhongkai Chen,Qinghua Zhan,Yifan Yan,Yanfei Cai,Zhaoqi Yang
Graphical With the development of nanoscience, nanotechnology has been used more and more in cancer treatment. As a rare and challenging type of breast cancer, triple-negative breast cancer has been poorly treated with multiple therapeutic modalities. Based on this, we synthesized a novel nanoparticle COF@ICG@GA, which can inhibit the expression of HSP90 under cell stress to enhance the temperature sensitivity of tumor cells, and cooperate with photothermal therapy to treat triple-negative breast cancer. The results of our experiment shows that the nanoparticles have inhibitory effect on tumor cells. Triple negative breast cancer (TNBC) represents a highly aggressive variant of breast cancer characterized by elevated rates of recurrence and mortality. Chemotherapy's application as a main cancer therapy is restricted due to its harmful side effects and resistance to medication. In this study, we utilized a covalent organic framework (COF) to apply indocyanine green (ICG), a photothermal agent, and gambogic acid (GA), an inhibitor of heat shock protein 90 (HSP90), to treat triple negative breast cancer. MTT results showed that the viability of tumor cells decreased more under laser irradiation conditions after the addition of GA than in the COF@ICG group. In addition, protein blotting results showed that under the action of GA, the blank group exhibited significantly higher HSP90 expression levels than the experimental group. The above results indicate that COF@ICG@GA enhances the therapeutic effect of PTT on cancer by inhibiting the expression of HSP90 in triple negative breast cancer cells and enhancing the sensitivity of tumor cells to temperature.
研究领域:
肿瘤学
·
纳米医学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
Materials Research Express
·
2019
·Vol. 6
·期 10
·105413
·
IF 1.449
Ke Song,Xin Wang,Xiao Liang,Mingxia Liu,Yang Zhou,Guolin Zhang,Lijiang Chen
The present study aims to develop a novel intelligent polymer-drug conjugate for the delivery of gambogic acid (GA). Specifically, the conjugate was composed of polyacrylic acid, GA and cystamine. GA-loaded nanoparticles (polyacrylic acid-cystamine-gambogic acid-nanoparticles, PAA-SS-GA-NPs) were simply and rapidly prepared using an ultrasonic-assisted direct dissolution method. Subsequently, we characterized the formulation by different methods, including dynamic light scattering (DLS), differential scanning calorimetry (DSC), transmission electron microscopy (TEM) and ultraviolet spectrophotometry (UV). Moreover, the in vitro release, cytotoxicity and cellular uptake were equally determined. The results showed that PAA-SS-GA-NPs had a small particle size (91.5 ± 9.19 nm), had a high drug loading efficiency ((32.5 ± 2.3) %) and greatly improved the water solubility of GA (over 9700-fold). Most importantly, they showed good response performance. The nanoparticles maintained the antitumor activity of GA but were less cytotoxic to normal cells than free GA. These results demonstrated that the nanoparticles may be a promising drug carrier.
研究领域:
药剂学
·
生物材料
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2018
·Vol. 7
·期 3
·1028-1042
·
IF 5.831
Fulei Liu,Xiaoxian Huang,Lingfei Han,Mangmang Sang,Lejian Hu,Bowen Liu,Bingjing Duan,Pan Jiang,Xin Wang,Zhou Qiao,Congyu Ma,Wenyuan Liu,Jun Liu,Feng Feng,Wei Qu
Gambogic acid (GA) is a natural antitumor drug candidate with advantages of broad-spectrum activity, low toxicity and multiple mechanisms. Its clinical application is hindered, however, by low aqueous solubility, instability and poor pharmacokinetic properties. In this research, core–shell hybrid nanoparticles have been developed to improve the druggability of GA. The nanoparticles are composed of a benzylamidated poly(γ-glutamic acid) (BzPGA) derivative as a core material and an amphiphilic hyaluronic acid derivative grafted with all-trans retinoic acid (HA-C6-ATRA) as a shell material. Through π–π stacking interactions, GA is encapsulated into BzPGA to form the “core” of the hybrid nanoparticle and the “shell” is formed by HA-C6-ATRA with a π–π stacking mediated “molecular fence”. The nanovehicle, with sub 100 nm size, provides almost 100% encapsulation efficiency, a good protective effect and a sustained release profile for GA. A series of evaluations suggest that the core–shell nanoparticles provide a stable aqueous injection formulation (I), improved stability (II), prolonged circulation time and conferred tumor targeting properties (III) for GA. As a result, the anti-tumor activity of GA is significantly enhanced without causing higher toxicity, indicating that the designed nanoplatform dramatically improves the druggability of GA. This study may also provide inspiration for drug development research.
研究领域:
药学
·
纳米技术
·
药物递送系统
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Zhen Zhang,Hanqing Qian,Mi Yang,Rutian Li,Jing Hu,Li Li,Lixia Yu,Baorui Liu,Xiaoping Qian
Gambogic acid (GA) is expected to be a potential new antitumor drug, but its poor aqueous solubility and inevitable side effects limit its clinical application. Despite these inhe rent defects, various nanocarriers can be used to promote the solubility and tumor targeting of GA, improving antitumor efficiency. In addition, a cell membrane-coated nanoparticle platform that was reported recently, unites the customizability and flexibility of a synthetic copolymer, as well as the functionality and complexity of natural membrane, and is a new synthetic biomimetic nanocarrier with improved stability and biocompatibility. Here, we combined poly(lactic-co-glycolic acid) (PLGA) with red blood-cell membrane (RBCm), and evaluated whether GA-loaded RBCm nanoparticles can retain and improve the antitumor efficacy of GA with relatively lower toxicity in colorectal cancer treatment compared with free GA. We also confirmed the stability, biocompatibility, passive targeting, and few side effects of RBCm-GA/PLGA nanoparticles. We expect to provide a new drug carrier in the treatment of colorectal cancer, which has strong clinical application prospects. In addition, the potential antitumor drug GA and other similar drugs could achieve broader clinical applications via this biomimetic nanocarrier.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Mingyue Ruan,Xinran Wang,Mingxue Guo,Zucheng Hu,Wenjun Hu,Zishuo Guo,Wanling Chen,Shiyan Li,Kai Wu,Shouying Du,Ning Han
Combined chemo-phototherapy has shown considerable advantages and potential in cancer treatment. For this purpose, self-assembled nanoparticles by gambogic acid (GA) and IR780 (referred to as GA-IR780 NPs) were prepared. Herein, GA, an active compound derived from Garcinia hanburyi Hook.f, was selected as a chemo-agent. IR780 was used as a photothermal agent as well as a photosensitizer, which could kill tumor cells via photothermal effect and photodynamic effect. The obtained GA-IR780 NPs were uniform spheres with particle size of ca. 50 nm. The drug loading efficiency of GA and IR780 was 38.42 % and 56.64 %, respectively. The GA-IR780 NPs exhibited excellent photothermal properties as well as photodynamic effect when irradiated by near infrared (NIR) light (808 nm, 2.0 W/cm 2 ). Moreover, the GA-IR780 NPs showed enhanced cytotoxicity with NIR light activation. Results of animal experiments showed that GA-IR780 NPs had the most significant tumor inhibition when irradiated by laser, and the results of H&E , Ki-67 and TUNEL staining confirmed that the GA-IR780 NPs+Laser group caused the most severe tumor tissue damage. The above results indicated that GA-mediated chemotherapy combining with IR780-based phototherapy could significantly improve the anti-tumor efficacy.
研究领域:
药学
·
癌症研究
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2020
·
IF 4.389
Zhoujiang Chen,Guanghui Hong,Zhiyan Liu,Dayun Yang,Ranjith Kumar Kankala,Wenguo Wu
Despite the success, the applicability of traditional chemotherapy still faces several challenges in treating cancer-related ailments, such as enormous toxicity and adverse effects. Combinatorial chemotherapy at reduced doses can offer augmented therapeutic efficiency through multiple mechanisms and even substantially circumvents the issues of toxicity and adverse effects. To demonstrate these facts, herein, two kinds of antitumor drugs, doxorubicin (DOX) and gambogic acid (GA), are encapsulated in bovine serum albumin (BSA) nanoparticles distinctly, resulting in DNP and GNP, respectively. These drug-loaded albumin nanocomposites, DNPs, and GNPs, showed a synergistic effect in ablating HepG2 tumor cells at a combination index (CI) of 0.38. Further, the ex vivo fluorescence imaging investigation confirmed the enriched drug internalization in the tumor precisely, which could be due to the enhanced permeation and retention (EPR) effect, resulting in the augmented therapeutic efficiency of designed nanoformulation. Notably, the synergistic tumor inhibition efficacy is more significantly attained at a 3-fold lesser dose of combined treatment than that of single full dose treatment in vivo . As anticipated, these conditions resulted in reduced organ toxicity. Together, this combinatorial strategy using BSA-based composites is an appropriate approach for application in medicine.
研究领域:
肿瘤学
·
药学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2019
·Vol. 33
·期 5
·1579-1591
·
IF 3.766
Li Wan,Qun Zhang,Sheng Wang,Yong Gao,Xiaofei Chen,Yang Zhao,Xiaoping Qian
Angiogenesis is central to a wide range of physiological and pathological processes including wound healing, macular degeneration, and cancer. Excessive or inappropriate vascular supply of tumors is one of the main targets for cancer therapy. Recently, critical and selective transcriptional factors such as yes-associated protein (YAP) that control the expression of angiogenesis factors have gained increasing attention in antiangiogenic therapy. In this study, we have identified and characterized a novel inhibitor of YAP, gambogic acid (GA), which exerted striking antiangiogenic effects both in vitro and in vivo. We demonstrated that GA remarkably inhibited a variety of vascular endothelial growth factor-induced angiogenesis processes including proliferation, migration, sprouting, and tube formation of endothelial cells in vitro. In addition, GA resulted in decreased neo-vessel formation in Matrigel plugs of mice and chick chorioallantoic membrane. More importantly, we showed that GA limited tumor growth via preventing tumor angiogenesis and vascular maturation. Further mechanistic studies illustrated that GA directly targeted YAP/STAT3 signaling axis, which is critical for the transcriptional regulation of a series of angiogenic factors. Taken together, these preclinical findings suggest that GA significantly repressed tumor angiogenesis and may serve as a promising drug candidate against cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2025
·
IF 12.1
Guoqin Huang,Lianying Zhang,Jiahao Feng,Dan Wu,Libo Wu,Weilun Pan,Yu Jiang,Ming Chen,Jinxiang Chen,Pixian Shui
Covalent organic frameworks (COFs), known for their exceptional in situ encapsulation and precise release capabilities, are emerging as pioneering drug delivery systems. This study introduces a hypoxia-responsive COF designed to encapsulate the chemotherapy drug gambogic acid (GA) in situ. Bimetallic gold-palladium islands were grown on UiO-66-NH 2 (UiO) to form UiO@Au-Pd islands (UAPi), which were encapsulated with GA through COF membrane formation, resulting in a core-shell structure (UAPiGC). Further modification with hyaluronic acid (HA) created UiO@Au-Pd islands @GA-COF@HA (UAPiGCH) for enhanced tumor targeting. In the hypoxic tumor microenvironment, the COF collapses, releasing GA and UAPi, initiating a triple therapeutic response: nanozyme-catalyzed therapy, near-infrared II (NIR-II) mild photothermal therapy (mild-PTT), and chemotherapy. UAPi exhibits catalase (CAT)-like and peroxidase (POD)-like activities, generating oxygen to alleviate hypoxia and reactive oxygen species (ROS) for tumor destruction. GA acts as a chemotherapeutic agent and inhibits heat shock protein 90 (HSP90), enhancing photothermal sensitivity. In vitro and in vivo studies confirm UAPiGCH’s ability to induce pyroptosis, stimulate dendritic cell maturation, and boost T cell infiltration, demonstrating its potential as a precise therapeutic nanoplatform. This strategy integrates multiple therapies into a hypoxia-responsive system, offering promising applications in cancer treatment.
研究领域:
癌症治疗
·
药物递送系统
·
纳米医学
·
免疫疗法
✓ 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）