International Journal of Nanomedicine
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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.
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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.
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PHYTOTHERAPY RESEARCH
·
2019
·Vol. 33
·期 5
·1579-1591
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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.
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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.
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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.
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Scientific Reports
·
2026
·Vol. 16
·期 1
·16800
·
IF 4.9
Rong Wenqing,Zhang Minquan,Yang Siqi,Wang Kaiwen,Yang Xiaoping,Zhang Guolei,Li Zhe,Ding Yue,Zhang Tong,Gai Yun,Lan Jinshuai
Breast cancer (BC), the most common cancer in women, is closely related to ferroptosis, which is an iron-dependent form of cell death. Gambogic acid (GA), the main active ingredient extracted from the dry resin secreted by Garcinia cambogia, can effectively induce ferroptosis in tumor cells. However, its application is limited by poor water solubility, short half-life, and vascular irritation. Moreover, the sensitivity of cells to ferroptosis is positively correlated with the concentration of intracellular iron ions, which based on transferrin (Tf)-Tf receptor (TfR) pathway. Increasing intracellular iron ions within tumor cells may enhance GA-induced ferroptosis. Based on the high expression of TfR in tumor cells, Tf can be both a tumor-target modification and an Fe 3+ carrier. Therefore, GA-loaded Tf-modified liposomes (GA@Tf-Lip) with pH-responsive properties were developed. GA@Tf-Lip increased the intracellular iron ion content of MCF-7 cells, promoted the Fenton reaction to increase the level of ROS, downregulated the GSH content, and accelerated lipid peroxide accumulation. The distribution of the formulation by in vivo imaging experiments showed that the prepared GA@Tf-Lip had a higher drug accumulation at tumor sites and exhibited a good antitumor effect by promoting ferroptosis. Overall, GA@Tf-Lip exerted a good anti-BC effect, which is expected to provide a new strategy for the treatment of BC and the clinical transformation of GA.
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International Journal of Nanomedicine
·
2023
·
IF 8
Yuling Liu,Xin Nie,Yihan Wu,Longfei Lin,Qian Liao,Jingjing Li,Simon Ming-Yuen Lee,Hui Li,Jinming Zhang
Introduction: The insufficient targeting delivery of therapeutic agents greatly impeded the treatment outcomes of rheumatoid arthritis (RA). Despite the recognized therapeutic advantages of gambogic acid (GBA) in inflammatory diseases, its high delivery efficiency to inflammatory site still limits its clinical application. Self-assembly of drug dimers into carrier-free nanoparticles (NPs) has become a straightforward and attractive approach to develop nanomedicines for RA treatment. Herein, homodimers of GBA were designed to form the carrier-free NPs by self-assembly for RA treatment.
Methods: The synthetic gambogic acid dimers (GBA2) were self-assembled into NPs using a one-step solvent evaporation method. The size distribution, morphology, drug-loading efficiency (DLE) and storage stability were evaluated. A molecular dynamic simulation was conducted to gain further insight into the self-assembly mechanisms of GBA2/NPs. Besides, we investigated the cytotoxicity, apoptosis and cellular uptake profiles of GBA2/NPs in macrophages and osteoclasts. Finally, the specific biodistribution on the ankles of adjuvant-induced arthritis (AIA) mice, and the anti-RA efficacy of the AIA rat model were assessed.
Results: GBA2/NPs exhibited the uniform spherical structure, possessing excellent colloidal stability, high self-assembly stability, high drug loading and low hemolytic activity. Comparing with GBA, GBA2/NPs showed higher cytotoxicity, cellular uptake and apoptosis rate against osteoclasts. In addition, GBA2/NPs exhibited much higher accumulation in ankle joints in vivo. As expected, the systematic administration of GBA2/NPs resulted in the greater alleviation of arthritic symptoms, cartilage protection, and inflammation, notably the reduced systemic toxicity compared to free GBA.
Conclusion: GBA2/NPs formed GBA dimers exhibited the superior accumulation in the inflamed joint and anti-RA activity, potentially attributing to the similar extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration (""ELVIS"") effects in inflamed joint and the enhanced cellular uptake in macrophages and osteoclasts. Our findings provide substantial evidence that self-assembly of GBA2/NPs would be a promising therapeutic alternative for RA treatment.
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MOLECULAR PHARMACEUTICS
·
2014
·
IF 4.787
Dengke Yin,Ye Yang,Hanxu Cai,Fei Wang,Daiyin Peng,Liqing He
This study aims to assess the targeted effect and antitumor efficacy of Gambogic-acid-loaded particles (GA-Ps). GA-Ps with uniform particle sizes of 69.8 ± 17.8 nm (GA-P1), 185.6 ± 33.8 nm (GA-P2), 357.8 ± 81.5 nm (GA-P3), and 7.56 ± 0.95 μm (GA-P4) were prepared using an electrospray technique and exhibited extremely high entrapment efficiency. As the particle size increased from the nano- to microscale, the in vitro GA release rate sharply decreased. After tail-vein injection in mice, GA-P samples GA-P1, GA-P2, GA-P3, and GA-P4 improved the uptake of GA 1.67-times in the liver, 1.78-times in the liver, 2.18-times in the spleen, and 2.35-times in the lung, respectively, compared with GA solution (GA-S). The antitumor efficacy of GA-P2, with an 82.51% targeting efficiency (Te) for the liver, was examined in hepatocellular carcinoma (HCC) model mice. After 2 weeks of administration, HCC mice in the GA-P2 group exhibited a lower degree of tumor invasion and cell lesions in hepatic tissue, recovered liver function, and significantly prolonged survival time, compared with mice in the model, GA-S, and normal saline (NS) groups. Pharmacokinetic studies indicated that the superior antitumor efficacy of GA-P2 was attributed not only to tissue targeting but also to low clearance, extended retention, high bioavailability in plasma, and increased GA stability.
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RSC Advances
·
2025
·Vol. 15
·期 55
·47506-47519
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IF 4.6
Liuqi Sang,Qun Zhang,Zixin Liang,Xinyi Xu,Xueying Bai,Ning Wang,Xingzhi Han,Li Li,Jing Hu,Xiaoping Qian
Delivering anti-tumor drugs to the correct location is an important strategy for improving tumor treatment efficacy and reducing side effects. To this end, this study developed a P-selectin-targeted drug delivery platform, where fucoidan-modified PLGA nanoparticles were loaded with the anti-tumor drug gambogic acid (GA) to form a novel nanoparticle, Fucoidan-PLGA/GA NPs (FPG). Fucoidan serves as a natural hydrophilic shell, enabling specific dual-targeting by binding to P-selectin overexpressed on tumor vascular endothelial cells and tumor cells, allowing FPG to cross the vascular barrier and reach the tumor tissue. In vitro and in vivo experimental results demonstrate that FPG has excellent binding capability to tumor cells and endothelial cells. The radiation-induced differential expression of P-selectin further enhances drug-targeted delivery. FPG combined with radiotherapy exhibited significant advantages in inhibiting tumor growth, inducing apoptosis, reducing tumor volume, modulating the immune microenvironment, and promoting cell phagocytosis. This targeted delivery system holds great potential for improving tumor treatment efficacy and reducing side effects in future cancer therapies.
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Pharmaceutics
·
2026
·Vol. 18
·期 2
·253
·
IF 6.9
Xiwen Zeng,Sizhuo Liu,Qianhui He,Yanwen Ling,Jingqi Sun,Yang Ping,Jin Su
Background: Liver cancer is a complex malignant tumor; gambogic acid (GA) has significant anti-cancer potential, but poor water solubility and low bioavailability limit its clinical application. In this paper, by integrating nanocrystal (NC) technology and an active targeting strategy, a new nanoagent—folic acid-modified phospholipid–gambogic acid nanocrystals (GA-NCs@FA)—was developed to improve the delivery efficiency and therapeutic effect of GA in the treatment of liver cancer.Methods: GA-NCs@FA was prepared by the CO2-assisted precipitation method and the thin-film hydration method. The in vitro anti-tumor activity of GA-NCs@FA was evaluated by cytotoxicity, as well as a scratch and uptake test. A HepG2 tumor-bearing nude mouse model was established to investigate the in vivo distribution and tumor targeting of GA. The in vivo anti-tumor activity was evaluated by the tumor inhibition rate, and the pathological changes of organs in each group were observed by H&E staining.Results: GA-NCs@FA significantly reduced HepG2 cell viability (IC50: 0.50 μg·mL−1) and migration ability (48 h healing rate: 11.50%) and enhanced intracellular fluorescence intensity. In vivo analysis showed that GA-NCs@FA significantly increased the accumulation of drugs in tumor tissues by active targeting and achieved a tumor growth inhibition rate of 70.9%. Histopathology confirmed that GA-NCs@FA induced the most obvious nuclear pyknosis and necrosis in tumor tissues while maintaining good biosafety.Conclusions: GA-NCs@FA significantly prolongs the systemic circulation time of the drug and enhances intratumoral accumulation; therefore, it is a method that can be considered for active targeting and treatment of liver cancer.
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Small
·
2024
·
IF 13
Jiaqi Liu,Hongmei Liu,Shan Huang,Hong Peng,Jiamei Li,Kerong Tu,Sumin Tan,Rou Xie,Lei Lei,Qin Yue,Huile Gao,Lulu Cai
Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype of breast cancer, characterized by aggressiveness and high recurrence rate. As monotherapy provides limited benefit to TNBC patients, combination therapy emerges as a promising treatment approach. Gambogic acid (GA) is an exceedingly promising anticancer agent. Nonetheless, its application potential is hampered by low drug loading efficiency and associated toxic side effects. To overcome these limitations, using mesoporous polydopamine (MPDA) endowed with photothermal conversion capabilities is considered as a delivery vehicle for GA. Meanwhile, GA can inhibit the activity of heat shock protein 90 (HSP90) to enhance the photothermal effect. Herein, GA-loaded MPDA nanoparticles (GA@MPDA NPs) are developed with a high drug loading rate of 75.96% and remarkable photothermal conversion performance. GA@MPDA NPs combined with photothermal treatment (PTT) significantly inhibit the tumor growth, and effectively trigger the immunogenic cell death (ICD), which thereby increase the number of activated effector T cells (CD8 + T cells and CD4 + T cells) in the tumor, and hoist the level of immune-inflammatory cytokines (IFN- γ , IL- 6 , and TNF- α ). The above results suggest that the combination of GA@MPDA NPs with PTT expected to activate the antitumor immune response, thus potentially enhancing the clinical therapeutic effect on TNBC.
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BULLETIN DU CANCER
·
2023
·
IF 1.2
Siyan Zhang,Xingyao Zhang,Dong Zhang,Liang Wei,Bin Xiong,Qi Meng,Shougang Jiang
Summary Introduction Gambogic acid (GA) as an active compound isolated from Gamboge, have been investigated for many years and proved to be a promising natural anticancer agent for clinical treatment . This study aimed to investigate the inhibitory effect of docetaxel (DTX) combined with gambogic acid on bone metastasis of lung cancer. Methods The anti-proliferation effect of the combination of DTX and GA on Lewis lung cancer (LLC) cells was determined by MTT assays . The anticancer effect of the combination of DTX and GA on bone metastasis of lung cancer in vivo was explored. Evaluation of the efficacy of drug therapy was performed by comparing the degree of bone destruction and the pathological section of bone tissue of the treated mice with that of the control mice. Results In vitro cytotoxicity, cell migration, and osteoclast-induced formation assay showed that GA enhanced the therapeutic effect of DTX in Lewis lung cancer cell with a synergistic effect. In an orthotopic mouse model of bone metastasis, the average survival of the DTX + GA combination group (32.61d ± 1.06 d) was significantly increased compared with that of the DTX group (25.75 d ± 0.67 d) or GA group (23.99 d ± 0.58 d), * P < 0.01. Conclusion The combination of DTX and GA has synergistic effect and resulted in more effective inhibition of tumor metastasis , providing a strong preclinical rationale for the clinical development of the DTX + GA combination for treating bone metastasis of lung cancer.
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