Asian Journal of Pharmaceutical Sciences
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2026
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IF 12.6
Xinying Wang,Xianlu Zhang,Zixuan Jiao,Shipeng Ning,Hanping Wang,Hui Liu,Lifen He,Haonan Li,Mingzhong Li,Kaiyuan Wang,Zhonggui He,You Pan
The treatment of triple-negative breast cancer (TNBC) is significantly hampered by its immunosuppressive tumor microenvironment and limited T-cell infiltration. Activating the STING pathway presents a promising therapeutic avenue due to its potential to trigger a robust innate immune response and remodel the immunosuppressive landscape, thereby sensitizing tumors to immunotherapy. To harness this potential, we developed an exosome-mimetic nanoplatform (EMMDs). EMMDs is fabricated by co-loading a disulfide-linked docetaxel prodrug (DTX-SS-PA) and the STING agonist MSA-2 into polymeric micelles and further decorated with homotypic tumor cell-derived exosomal membrane (EM). This biomimetic design confers superior tumor-targeting capability. Upon reaching the tumor site, the prodrug is specifically activated to release cytotoxic docetaxel (DTX), while MSA-2 is concurrently released to potently activate the STING pathway. This dual action initiates a powerful antitumor immune response and reverses immunosuppression, leading to a synergistic chemo-immunotherapeutic outcome. In the murine TNBC model, EMMDs demonstrated remarkable antitumor efficacy, obviously provoking a robust STING-mediated type I interferon response and inhibiting tumor growth. This work presents a promising biomimetic strategy for remodeling the tumor immune microenvironment via efficient STING activation.
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高影响因子
Drug Delivery and Translational Research
·
2019
·Vol. 10
·期 1
·122-135
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IF 3.111
Lu Xiaoyu,Fang Min,Yang Yue,Dai Yu,Xu Jiaqiu,Zhao Di,Lu Yang,Chen Xijing,Lu Shan,Li Ning
PEGylated triacontanol (mPEG 2k -b-TRIA) was developed as a dual-functional polymer with remarkable biocompatibility. The polymer could self-assemble to micelles with critical micelle concentration (CMC) 17.62 μg mL −1 . Docetaxel-loaded mPEG 2k -b-TRIA micelles (DTX PMs) were fabricated to evaluate the feasibility of mPEG 2k -b-TRIA as drug delivery system. DTX PMs achieved desirable particle size of 93.7 nm, drug loading of 6.66%, and drug encapsulation efficiency of 89.87%. The drug release was based on first-order kinetics model, thus enabling prolonged release. Meanwhile, pharmacokinetic study also revealed that DTX PMs could improve the exposure level of DTX and prolong its systemic circulation time. Furthermore, DTX PMs demonstrated significantly enhanced cytotoxicity and cellular uptake in vitro compared with DTX solution. The in vivo tumor inhibition study carried out on MCF-7 bearing BALB/c mice model also validated that DTX PMs exhibited stronger anti-tumor activity but low toxicity. Notably, mPEG 2k -b-TRIA made some contribution to inhibit the growth of breast cancer cells in vitro and in vivo, indicating the potential as anti-tumor complementary agents. All the results suggested that mPEG 2k -b-TRIA polymer as a vehicle in the formulation of anti-cancer drugs may provide an effective way to improve their therapeutic efficacy. Consequently, the mPEG 2k -b-TRIA polymers would be another promising carrier for hydrophobic anti-cancer drugs delivery.
研究领域:
药学
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肿瘤学
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药物递送系统
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纳米技术
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PubMed
高影响因子
AAPS PHARMSCITECH
·
2019
·Vol. 20
·期 7
·1-10
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IF 2.608
Xu Yingxin,Fang Tianxu,Yang Yifan,Sun Li’ang,Shen Qi
Docetaxel (DTX) was effective in the treatment of neoplasm but could only be administered intravenously with the poor oral bioavailability owing to its undesirable solubility, remarkably metabolic conversion, and other factors. Cimetidine (CMD), a classic CYP3A4 isozyme inhibitor, had exhibited a wide range of inhibition on the metabolism of many drugs. The aim of this study was to construct the novel docetaxel-cimetidine (DTX-CMD) complex and the chitosan-deoxycholate nanoparticles based on it to confirm whether this formulation could show advantages in terms of solubility, dissolution rate, small intestinal absorption, and oral bioavailability in comparison with the pure drug. The solid-state characterization was carried out by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), and simultaneous DSC-TGA (SDT). Dissolution rate and kinetic solubility study were determined by evaluating the amount of DTX in distilled water and phosphate buffer solution (pH = 7.4), respectively. And small intestinal absorption and pharmacokinetics study were conducted in rats. The results of this study demonstrated that we successfully constructed DTX-CMD complex and its chitosan-deoxycholate nanoparticles. Furthermore, the DTX-CMD complex increased the solubility of DTX by 2.3-fold and 2.1-fold in distilled water and phosphate buffer solution, respectively. The ultimate accumulative amount of DTX-CMD complex nanoparticles through rat small intestinal in 2 h was approximately 4.9-fold and the oral bioavailability of the novel nanoparticles was enhanced 2.8-fold, compared with the pure DTX. The superior properties of the complex nanoparticles could both improve oral bioavailability and provide much more feasibility for other formulations of DTX.
研究领域:
药剂学
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药物代谢动力学
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高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2020
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IF 4.389
XinHong Guo,JunYa Zhang,QingQing Cai,ShuTing Fan,QingQing Xu,JieYing Zang,HuiTing Yang,WenJuan Yu,Zhi Li,ZhenZhong Zhang
Nanoparticle-structuring aimed at the acetic acid (A) transporter on intestinal epithelial cells and tumor cells is a new potential strategy to enhance oral bioavailability and anti-tumor efficacy. In this study, chitosan (CS) was modified with hydrophilic A and hydrophobic lipoic acid (L), to produce ACSL. A novel ACSL-modified multifunctional liposomes (Lip) loaded with docetaxel (DTX; DTX-ACSL-Lip) was then prepared and characterized. DTX-ACSL-Lip recorded higher pH sensitivity and slower release than DTX-Lip and showed dithiothreitol (DTT) response release. DTX-ACSL-Lip uptake by Caco-2 cells was also significantly enhanced mainly via A transporters compared with DTX-Lip. ACSL modification of DTX-Lip also improved oral bioavailability by 10.70-folds, with a 3.45-fold increase in C max and a 1.19-fold prolongation in retention time of DTX in the blood. Moreover, the grafting degree of A significantly affected cell uptake and oral bioavailability. They also showed a significant (1.33-fold) increase in drug intratumoral distribution, as well as an increase in tumor growth inhibition rate from 54.34% to 87.51% without weight loss, compared with DTX-Lip. Therefore, modification of DTX-Lip with ACSL can significantly enhance the oral bioavailability and anti-tumor efficacy of DTX without obvious toxicity, confirming the potential of the dual strategy of targeting A transporter and controlled drug release in tumor cells in oral therapy of tumor.
研究领域:
药学
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生物技术
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药物递送系统
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肿瘤学
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高影响因子
DRUG DELIVERY
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2016
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IF 4.843
Guolian Ren,Dan Liu,Weiling Guo,Menglin Wang,Chunnuan Wu,Mengran Guo,Xiaoyu Ai,Yongjun Wang,Zhonggui He
There is a strong desire to develop docetaxel (DTX) formulation with good therapeutic effectiveness in view of serious adverse reactions of the commercial formulation of DTX (Taxotere®). In this study, a redox-responsive DTX-vitamin E prodrug was successfully formulated into liposomes with the drug loading of 4.14% ± 0.10%. Compared with DTX liposomes, the DTX prodrug liposomes (DPLs) showed good stability for 30-d shelf life and during dilution with different media. In vitro antitumor activity of DPLs on human prostatic carcinoma PC-3 cells and human lung cancer A549 cells was evaluated using cytotoxicity and apoptosis assays. In spite of a decrease in in vitro antitumor activity, the in vivo pharmacokinetic study reveals that DPLs exhibit significantly longer DTX plasma half-life (t1/2, 1.38-fold) and higher bioavailability (AUC0−t, 14.49-fold) compared with DTX liposomes. The antitumor activity of DPLs to the A549 tumor xenograft model showed selective accumulation in tumor tissue, significant inhibition the growth of the tumors and a much lower toxicity as seen in body weight loss, compared with DTX-Solution. Taken together, the results showed that DPLs is a promising strategy for DTX antitumor delivery.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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PubMed
高影响因子
Theranostics
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2017
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IF 8.766
Liwei Tan,Jinrong Peng,Qian Zhao,Lan Zhang,Xichuan Tang,Lijuan Chen,Minyi Lei,Zhiyong Qian
Satisfactory drug loading capacity and stability are the two main factors that determine the anti-cancer performance. In general, the stability of the micelles is reduced when the drug loading (DL) is increased. Therefore, it was a challenge to have high drug loading capacity and good stability. In this study, we introduced a hydrophilic poly (L-Lysine) (PLL) segment with different molecular-weights into the monomethoxy poly (ethylene glycol)-poly (D, L-lactide) (MPEG-PDLLA) block copolymer to obtain a series of novel triblock MPEG-PDLLA-PLL copolymers. We found that the micelles formed by a specific MPEG 2k -PDLLA 4k -PLL 1k copolymer could encapsulate docetaxel (DTX) with a satisfactory loading capacity of up to 20% (w/w) via the thin film hydration method, while the stability of drug loaded micellar formulation was still as good as that of micelles formed by MPEG 2k -PDLLA 1.7k with drug loading of 5% (w/w). The results from computer simulation study showed that compared with MPEG 2k -PDLLA 1.7k , the molecular chain of MPEG 2k -PDLLA 4k -PLL 1k could form a more compact funnel-shaped structure when interacted with DTX. This structure favored keeping DTX encapsulated in the copolymer molecules, which improved the DL and stability of the nano-formulations. The in vitro and in vivo evaluation showed that the DTX loaded MPEG 2k -PDLLA 4k -PLL 1k (DTX/MPEG 2k -PDLLA 4k -PLL 1k ) micelles exhibited more efficiency in tumor cell growth inhibition. In conclusion, the MPEG 2k -PDLLA 4k -PLL 1k micelles were much more suitable than MPEG 2k -PDLLA 1.7k for DTX delivery, and then the novel nano-formulations showed better anti-tumor efficacy in breast cancer therapy.
研究领域:
药剂学
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肿瘤学
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生物材料学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2018
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IF 3.862
Tao Zhang,Meng Li,Ruyi Yang,Dong Zhang,Jibin Guan,Jiang Yu,Bin Yang,Huicong Zhang,Shenwu Zhang,Dan Liu,Yongjun Wang
Docetaxel (DTX) solution is among the most widely-used parenteral formulations used in advanced breast cancer therapy. However, severe side effects have been observed due to the use of ethanol and polysorbate 80 . Herein, a novel DTX-based prodrug , docetaxel-linoleic acid conjugate (DTX-LA) was successfully synthesized. The high lipid solubility of DTX and DTX-LA resulted in a tendency for them to become entrapped in the oil core of the emulsions. As anticipated, nano-sized, sterically stabilized oil-in-water lipid emulsions (LMs) of DTX-LA LMs and DTX LMs were successfully constructed. Unlike DTX solution, LMs exhibited high colloidal stability and sustained-release behavior, having a narrow size distribution that was ∼220 nm in diameter. Compared with DTX LMs, DTX-LA LMs had a greater drug-loading capacity. Although the cytotoxicity of DTX-LA LMs was reduced in comparison with DTX solution, the pharmacokinetic study demonstrated increased bioavailability (p < 0.001) and half-life (p < 0.01). Finally, DTX-LA LMs displayed significant antitumor efficacy with reduced side effects in a 4T1 breast cancer xenograft model. Thus, the novel lipid emulsion-based docetaxel prodrug delivery system may be a promising strategy for improving intravenous administration for breast cancer treatment.
研究领域:
药学
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肿瘤学
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BIOMEDICINE & PHARMACOTHERAPY
·
2015
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IF 2.023
Liandong Hu,Saixi Pang,Qiaofeng Hu,Deliang Gu,Dongqian Kong,Xiaoyun Xiong,Jianying Su
Background The current study aimed to investigate whether the novel folate (FT) modified nanoparticles (NPs) co-loaded with docetaxel (DT) and curcumin (CU) (named as FT-NPs) could enhance the delivery efficiency to tumor compared with the NPs without FT (non-targeted NPs). Methods FT-NPs were successfully formulated in this article. In vitro cytotoxic activity against A549 cells and in vivo antitumor activity of FT-NPs in S180 cell bearing mice were conducted. Cellular uptake test was used to evaluate uptake efficiency of FT-NPs. Histological observation was used to determine the lung security. Besides, the physical chemical properties such as stability, particle size, zeta potential , drug encapsulation efficiency, transmission electron microscopy (TEM) were also conducted. Results FT-NPs exhibited stronger growth inhibition effects on A549 cells compared with non-targeted NPs, moreover, the novel FT-NPs indicated more effective antitumor efficacy in inhibiting tumor growth. Confocal laser scanning microscopy indicated that the uptake of FT-NPs was facilitated and effective. Histological observation meant that FT-NPs were biocompatible and appropriate for pulmonary administration. Conclusion These results confirmed that FT-NPs with relatively high drug loading capacity could effectively inhibit tumor growth and reduce toxicity. The novel FT-NPs could produce as an outstanding nanocarrier for the targeted treatment of cancers .
研究领域:
药学
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纳米技术
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肿瘤学
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生物医学工程
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PubMed
高影响因子
RSC Advances
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2015
·Vol. 5
·期 110
·90386-90395
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IF 3.84
Weihua Jiang,Ju Wang,Lei Yang,Xuewei Jiang,Zhaoshi Bai,Zheran Wang,Yunpeng He,Dongkai Wang
An amphiphilic carboxymethylcellulose-graft-histidine/methoxypolyethylene glycol (CMP) copolymer was firstly synthesized to modify nanostructured lipid carriers (NLCs), and the impact of this CMP modification on in vitro and in vivo behaviors of NLCs was investigated in detail. An obvious core–shell structure of CMP-coated nanostructured lipid carriers (CNLCs) was observed by a transmission electron microscope (TEM). Docetaxel (DTX) efficiently encapsulated in CNLCs formed 88.7 ± 1.11 nm particles with a negative zeta potential of −20.9 ± 1.11 mV. In vitro release studies indicated that the CMP coating significantly reduced the burst drug release at pH 7.4, whereas DTX-loaded CNLCs (DTX-CNLCs) could release the drug as quickly as DTX-loaded NLCs (DTX-NLCs) at pH 5.0. The pharmacokinetic performances proved that DTX-CNLCs had longer retention times in blood and higher area under the concentration–time curve (AUC) in rats than DTX-NLCs (p < 0.05). Furthermore, cell uptake, cytotoxicity, and cell apoptosis assays in MCF-7 cells consistently demonstrated that no obvious difference was found between DTX-CNLCs and DTX-NLCs (p > 0.05), indicating that this modification did not disturb effective killing of the cancer cells. As expected, DTX-CNLCs exhibited better antitumor effects than DTX-NLCs in the tumor-bearing nude mice (p < 0.05), due to their long circulation effect. Consequently, CNLCs hold great potential for effective delivery of anticancer drugs.
研究领域:
药学
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生物医学工程
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癌症研究
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高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Zhen Yu,Xundou Li,Jinhong Duan,Xian-Da Yang
Purpose Chemotherapy of colon cancer needs improvement to mitigate the severe adverse effects (AEs) associated with the cytotoxic drugs. The aim of this study is to develop a novel targeted drug delivery system (TDDS) with practical application potential for colon cancer treatment.Methods The TDDS was built by loading docetaxel (DTX) in albumin nanoparticles (NPs) that were functionalized with nucleolin-targeted aptamers (AS1411).Results The TDDS (Apt-NPs-DTX) had an average size of 62 nm and was negatively charged with a zeta potential of −31.2 mV. DTX was released from the albumin NP with a typical sustained release profile. Aptamer-guided NPs were preferentially ingested by nucleolin-expressing CT26 colon cancer cells vs the control cells. In vitro cytotoxicity study showed that Apt-NPs-DTX significantly enhanced the killing of CT26 colon cancer cells. Importantly, compared with non-targeted drug delivery, Apt-NPs-DTX treatment significantly improved antitumor efficacy and prolonged the survival of CT26-bearing mice, without raising systemic toxicity.Conclusion The results suggest that Apt-NPs-DTX has potential in the targeted treatment of colon cancer.
研究领域:
肿瘤学
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药学
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纳米技术
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癌症治疗
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PubMed
高影响因子
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.
研究领域:
肿瘤学
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药理学
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分子生物学
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PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Yanhao Zhang,Hao Zhang,Ji Wang,Chao Liu,Hanlei Xing,Yuhao Jiang,Xinsong Li
Docetaxel (DTX), a semisynthetic analogue of paclitaxel, is often used to treat cancers. Owing to its poor aqueous solubility, the current formulation of DTX for clinical applications involves using high surfactant and ethanol concentrations, causing hypersensitivity reactions. To overcome this issue, we developed a reduction-responsive DTX prodrug encapsulated within human serum albumin (HSA) nanoparticles (DTX–SS–COOH/HSA NPs). First, the DTX prodrug was conjugated to undecanoic acid through a disulfide bond (DTX–SS–COOH) via a four-step reaction. Subsequently, DTX–SS–COOH/HSA NPs were prepared via the desolvation method. The NPs exhibited a spherical structure with a diameter range of 140–220 nm, as revealed by dynamic light scattering and transmission electron microscopy. Fluorescence quenching analysis confirmed the formation of DTX–SS–COOH/HSA, which was ascribed to electrostatic interactions and hydrophobic forces. Notably, NPs with a feed mole ratio corresponding to DTX–SS–COOH/HSA = 9:1 demonstrated high drug-loading and encapsulation efficiency of 12.84 and 93.11%, respectively, alongside good stability. Moreover, the reduced responsiveness experiment revealed an accelerated DTX release in the presence of glutathione. An in vivo pharmacokinetic study indicated that DTX–SS–COOH/HSA NPs demonstrated considerably a prolonged circulation time (6.2-fold) compared to that of free DTX. Ultimately, the antitumor test of MDA-MB-231 tumor-bearing mice revealed that DTX–SS–COOH/HSA NPs were superior to DTX/HSA NPs for tumor growth inhibition. Thus, DTX–SS–COOH/HSA NPs represent a promising DTX nanoformulation for clinical application.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
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生物药剂学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）