Materials Science & Engineering C-Materials for Biological Applications
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2018
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IF 5.08
Xiang Feng,Yunfeng Zhou,Xin Xie,Ming Li,Hao Huang,Liangliang Wang,Xiao Xu,Jingmou Yu
In this study, prostate-specific membrane antigen (PSMA)-targeted and core-crosslinked micelles were developed based on prostate cancer-binding peptide (PCP) modified glycol chitosan-lipoic acid (PGC-LA) conjugate. The degree of substitution was 5.2 PCP groups and 10.7 lipoic acid groups per 100 sugar residues of glycol chitosan in PGC-LA copolymer. Docetaxel (DTX) was chosen as a model anti-tumor drug. The DTX-loaded micelles were prepared by an o/w method, and core-crosslinked micelles were further constructed by using a catalytic amount of dithiothreitol. The mean diameter of DTX-loaded core-crosslinked PGC-LA (DTX-PGC-LA/cc) micelles was 397 nm determined by dynamic light scattering (DLS). In vitro DTX released from core-crosslinked micelles was slower than that from non-crosslinked counterpart. Blank micelles exhibited good biocompatibility. Additionally, cellular uptake and cytotoxcity of PCP-modified micelles were higher than those of micelles without PCP in PSMA-positive LNCaP cells. Importantly, DTX-PGC-LA/cc demonstrated the stronger anti-tumor efficacy against LNCaP tumor xenograft models than DTX injection and other DTX-loaded micelles. Taken together, this study provides a potential way in developing actively targeted and core-crosslinked micelles for hydrophobic drug delivery in cancer therapy.
研究领域:
药剂学
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肿瘤学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2021
·
IF 7.328
Qiu-Ping Feng,Yu-Ting Zhu,Yi-Zhen Yuan,Wen-Jie Li,Hao-Han Yu,Meng-Yuan Hu,Su-Yun Xiang,Shu-Qin Yu
In this study, to improve the intestinal absorption of small molecule chemotherapeutic drug docetaxel (DTX) and macromolecular monoclonal antibody drug bevacizumab (BVZ), we designed and prepared a type of co-delivery nanoparticles for the oral administration of DTX and BVZ. Carboxymethyl chitosan (CMC) and poly(lactic- co -glycolic acid) (PLGA) were used as the carrier of DTX nanoparticles (CPNP DTX ), and methoxy polyethylene glycol-poly (β-amino ester) (mPEG-PAE) was used as the carrier of BVZ nanoparticles (PPNP BVZ ). Then, the two nanoparticles were physically mixed in mass ratios to form mixed co-delivery nanoparticles, which was named as CPNP DTX &PPNP BVZ . The nanoparticles were characterized with pH-sensitive drug release property. CPNP DTX &PPNP BVZ could significantly increase the bioavailability of DTX and BVZ according to the more cellular uptake in Caco-2 cells and the higher absorption in the intestinal tissue. Compared with free DTX and BVZ, CPNP DTX &PPNP BVZ showed excellent cytotoxic effects on A549 cells. Our study revealed the potential of co-delivery nanoparticles of binary mixture of chemotherapeutic small molecule and macromolecular antibody drug as an oral administration therapeutic system.
研究领域:
药学
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纳米技术
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
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2018
·
IF 1.492
Ao Man,Xiao Xu,Ao Yazhou
In the present study, we successfully developed a docetaxel (DTX) and thalidomide (TDD) co-delivery system based on low density lipoprotein (LDL) modified silica nanoparticles (LDL/SLN/DTX/TDD). By employing the tumor homing property of LDL and the drug-loading capability of silica nanoparticles, the prepared LDL/SLN/DTX/TDD was expected to locate and specifically deliver the loaded drugs (DTX and TDD) to achieve effective chemotherapy of liver cancer. In vitro analysis revealed that nano-sized LDL/SLN/DTX/TDD with decent drug loading capabilities was able to increase the delivery efficiency by targeting the low density lipoprotein receptors, which were overexpressed on HepG2 human hepatocellular liver carcinoma cell line, which exerted better cytotoxicity than unmodified silica nanoparticles and free drugs. In vivo imaging and anti-cancer assays also confirmed the preferable tumor-homing and synergetic anti-cancer effects of LDL/SLN/DTX/TDD.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2017
·
IF 4.44
Yiyue Wang,Jing Li,Jing Jing Chen,Xuan Gao,Zun Huang,Qi Shen
The polylactic-co-glycolic acid polyethylene glycol conjugated with cell penetrating peptide R7 (PLGA–PEG-R7)/polysulfadimethoxine-folate nanoparticles loaded with docetaxel (DTX) and GDC0941 (R7/PSD-Fol NPs) were prepared to overcome multidrug resistance (MDR) and enhance the antitumor activity. First, polysulfadimethoxine-folate was synthesized to construct the R7/PSD-Fol NPs. The R7/PSD-Fol NPs were prepared with the abilities of effective entrapment and drug loading. Due to the pH-sensitive effect of PSD-folate, the releasing of DTX and GDC0941 from the R7/PSD-Fol NPs was lower in pH 7.4 buffer solution than that in pH 5.0 buffer solution. The half maximal inhibitory concentration (IC50) of MCF-7 and resistant to doxorubicin (MCF-7/Adr) cells illustrated the cytotoxicity of R7/PSD-Fol nanoparticles by using the MTT method. The uptake of R7/PSD-Fol NPs was visualized by using the fluorescence of Rh-123 to detect the targeting effect of folate on the surface of R7/PSD-Fol NPs. The results of the cell apoptosis and the depolarization of mitochondrial membrane potential (MMP) were adopted to show the cytotoxicity of the R7/PSD-Fol NPs on MCF-7/Adr cells. The Western blot revealed the inhibition of PI3K/Akt pathway in MCF-7/Adr cells induced by R7/PSD-Fol NPs. Finally, both in vivo distribution and in vivo antitumor showed the R7/PSD-Fol NPs displayed the better distribution at tumor site and the stronger suppression of tumor growth in the tumor bearing nude mice compared with control group. It was concluded that R7/PSD-Fol NPs loaded with DTX and GDC0941 could overcome MDR and enhance the antitumor effect further.
研究领域:
药理学
·
肿瘤学
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纳米技术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2016
·
IF 3.994
Jing Wang,Peng Xue,Jiahua Zhou,Lin Li,Lu Xu,Yongjun Wang
To achieve optimal therapeutic index of docetaxel , we conjugated docetaxel (DTX) with vitamin E (VE) by ester bond with disulfide bond or thioether bond as spacer to produce DTX-ss-VE or DTX-s-VE. The two prodrugs were successfully loaded into liposomes . The physicochemical characterization and in vitro release profiles of the prodrug loaded liposomes were investigated. MTT assays showed that the cytotoxicity of DTX-ss-VE loaded liposomes on PC3 (IC 50 = 27.5 nM) and A549 cells (IC 50 = 63.4 nM) was comparable with the cytotoxicity of DTX-s-VE loaded liposomes (IC 50 = 99.2 and 159.5 nM, respectively). The pharmacokinetic studies demonstrated that DTX-ss-VE and DTX-s-VE loaded liposomes exhibited an extended DTX half-life (3.6 ± 1.2 and 10.0 ± 3.0 h, respectively) as compared to DTX solutions (2.1 ± 1.5 h) and an increased AUC (30487.3 ± 3791.6 and 20922.1 ± 5633.3 ng/L × h, respectively) compared with DTX solutions (1779.3 ± 226.6 ng/L × h). Finally, the in vivo anti-tumor studies showed that DTX-ss-VE loaded liposomes possessed similar antitumor activity compared with DTX solutions. Unexpectedly, not any tumor inhibition effect was observed in DTX-s-VE loaded liposomes group. In a conclusion, our studies suggested that simplex favorable properties of the anticancer prodrug can not ensure available good therapeutic index and the rational design of prodrug needs a comprehensive understanding of the in vitro and in vivo behavior of the prodrug.
研究领域:
药理学
·
肿瘤学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oncotarget
·
2016
·
IF 5.008
Tao Liu,Xidong Wu,Yigang Wang,Tao Zhang,Ting Wu,Fang Liu,Wansong Wang,Gang Jiang,Minqiang Xie
The co-delivery of drug and gene has become the primary strategy in cancer therapy. Based on our previous work, to co-deliver docetaxel (DOC) and MMP-9 siRNA more efficiently for HNE-1 nasopharyngeal carcinoma therapy, a folate-modified star-shaped copolymer (FA-CD-PLLD) consisting of β-cyclodextrin (CD) and poly(L-lysine) dendron (PLLD) was synthesized, and then used for DOC and MMP-9 co-delivery. Different from commonly used amphiphilic copolymers micelles, the obtained CD derivative could be used directly for the combinatorial delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vitro and in vivo assays are carried out to confirm the effectiveness of the target strategy and combined treatment. It was found that the conjugation of CD-PLLD with FA could enhance the DOC/MMP-9 delivery effect obviously, inducing a more significant apoptosis and decreasing invasive capacity of HEN-1 cells. In vivo assays showed that FA-CD-PLLD/DOC/MMP-9 could inhibit HNE-1 tumor growth and decrease PCNA expression effectively, indicating a promising strategy for nasopharyngeal carcinoma therapy. Moreover, the in vivo distribution of DOC and MMP-9, blood compatibility and toxicity are also explored.
研究领域:
药剂学
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2022
·
IF 3.682
Yongli Shi,Chunyan Li,Mingbo Yang,Xiaofei Pan,Jie Hu
In this study, novel redox-sensitive nanoparticles (NPs) were fabricated from the poly(caprolactone) conjugates with disulfide-linked poly(ethylene glycol) (DDMAT- mPEG-S-S-PCL, DPSP). The DPSP polymer was synthesized by ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. The obtaining of the DPSP polymer was confirmed by the 1H nuclear magnetic resonance (1H NMR) and Fourier transform infrared spectroscopy (FTIR) spectra. The DPSP NPs were fabricated with the solvent-evaporation method. Docetaxel (DTX) was employed as a model drug and encapsulated into the DPSP NPs. The in vitro anti-tumor activity of the DTX-loaded DPSP NPs and free DTX against the breast cancer cells (4T1) were evaluated by MTT assay. The cargo-free DPSP NPs were in circular shapes with an average diameter of 107.8 ± 0.4 nm. These NPs displayed redox-responsive behavior in the presence of glutathione. Animal experiments indicated that the DPSP NPs showed excellent blood compatibility and good bio-security. Cell tests suggested that the DPSP NPs could be taken in by 4T1 cells, smoothly, which improved the anti-tumor activity of free DTX.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2026
·
IF 5.8
Heng Zhang,Hua Ni,Mengqi Peng,Tian Chen,Lu Ge,Xueying Zhang,Kai Tian,Yi Sun
BackgroundDematiaceous fungal infections are frequently encountered in clinical practice with no unified treatment. Drug combination reduces drug resistance, and repurposed clinical drugs as synergists show promise in aiding azoles against phaeohyphomycosis.ObjectiveTo investigate the synergistic antifungal effects of docetaxel (DTX) in combination with azoles against dematiaceous fungi and Aspergillus niger, as well as their impact on efflux pump activity.MethodsCLSI M38-A2 microbroth dilution method was used to detect fractional inhibitory concentration index of DTX with posaconazole (POS), itraconazole (ITC), voriconazole (VOR), and isavuconazole (ISA) against 43 fungi (including 24 strains of Exophiala dermatitidis, 7 strains of Exophiala alcalophila, 3 strains of Fonsecaea pedrosoi, 1 strain of Fonsecaea monophora, 1 strain of Exophiala verrucosa and 7 strains of Aspergillus niger). Rhodamine 6G transport efficiency and transcriptional variations of efflux pump genes were determined in strains treated with POS alone or POS combined with DTX.ResultsDTX alone had no antifungal activity. 30/43 (69.8%) strains showed synergy with POS (87.5% E. dermatitidis, 100% A. niger). 7 (16.3%), 3 (7.0%) and 1 (2.3%) strains showed synergy with ITC, VOR and ISA. For strains with POS synergism, DTX treatment significantly suppressed efflux activity and modified the transcription of efflux pump genes.ConclusionThe combined scheme of DTX and POS can significantly reduce the minimum inhibitory concentration of POS and show synergistic antifungal activity, especially significant against E. dermatitidis and A. niger. Its mechanism of action may be related to the reduction of efflux pump activity.
✓ 已验证
DOI
高影响因子
Materials Today Bio
·
2026
·
IF 11
Xueying Bao,Huanhuan Wang,Man Li,Zhuangzhuang Zheng,Xuanzhong Wang,Jianfeng Guo,Xin Jiang
Docetaxel (DTX)-based concurrent chemoradiotherapy (CCRT) is an important treatment for locally advanced non-small cell lung cancer (NSCLC), but its efficacy is limited by systemic toxicity and radioresistance. Here, we propose an oxidative priming strategy using plumbagin (PLB), a natural redox modulator, to disrupt tumor redox homeostasis and enhance DTX-mediated chemoradiotherapy. PLB markedly sensitized NSCLC cells to DTX, reducing the effective DTX concentration by 33.3-fold in LLC cells and 18-fold in A549 cells. To overcome the pharmacokinetic mismatch between DTX and PLB, we developed a folate receptor-targeted PEGylated liposomal nanoformulation for synchronized co-delivery. This formulation amplified intracellular ROS accumulation to approximately 2.5 times that induced by X-ray alone and 3.3 times that induced by (DTX + PLB)-NP alone, thereby enhancing radiation-induced DNA damage and apoptosis. In vivo, X-ray combined with the targeted nanoformulation achieved a tumor inhibition rate of 99%, while maintaining stable body weight and showing no obvious hematological, hepatic, or renal toxicity. This study provides a redox-guided nanomedicine strategy to enhance DTX-based CCRT for NSCLC at low doses while maintaining favorable preliminary biosafety.
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2026
·
IF 11
Zang Xin,Liu Dezhi,Zhang Jingyi,Chao Xuyuan,Chen Xin,Yang Shengjie,Fang Yingying,Li Yan,Li Yinjuan,Qi Lu,Wang Xinghe
In triple-negative breast cancer (TNBC), tumor-associated macrophages (TAMs) and tumor-infiltrating dendritic cells (TIDCs) often exhibit an immunosuppressive phenotype. This myeloid-dominant milieu reinforces an immune-cold state, promotes metastasis and contributes to immunotherapy resistance. In this study, we developed a mannose-functionalized graphene oxide nanocarrier (GO-EDM) with favorable biocompatibility and high NIR photothermal conversion efficiency. Docetaxel and vadimezan (DMXAA), a prototypical STING agonist, were co-loaded into GO-EDM to generate GO-EDM-DTX-Vad. In vitro, the nanocomposite promoted M2-to-M1 repolarization, thereby attenuating pro-tumor paracrine signaling from M2 macrophages and limiting TNBC cell proliferation, migration and invasion. Concomitantly, it promoted dendritic cell maturation and induced immunogenic cell death (ICD) in tumor cells, collectively enhancing antigen presentation and T-cell activation. In vivo, both intratumoral administration and systemic intravenous administration of GO-EDM-DTX-Vad effectively suppressed primary tumor growth. In a lung metastasis model, when combined with 808 nm NIR irradiation, the pulmonary metastatic burden was significantly reduced. Specifically, this treatment reduced the accumulation of M2 macrophages, MDSCs and Tregs within tumors, while promoting DC maturation and increasing intratumoral infiltration of M1 macrophages, CD8 + T cells and memory T cells. Taken together, GO-EDM-DTX-Vad leverages passive tumor accumulation and mannose receptor–guided dual targeting of TAMs and TIDCs to integrate DTX-based chemotherapy, STING-mediated immune activation and mild NIR photothermal therapy. This integrated chemo–photothermal–immunotherapeutic design couples direct tumor cell killing with myeloid reprogramming and immune activation, offering a unified strategy for metastatic TNBC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Wenxiao Li,Haiyu Zhao,Jiayu Guo,Xianbao Shi,Yixin Sun,Zhonggui He,Bingjun Sun
The modular engineering of prodrug nanoassemblies—integrating drug modules, response modules, and modification modules—has emerged as a promising platform for cancer nanomedicines. Despite advances, the mechanistic link between modification modules and the in vivo fate of nanoassemblies remains undefined, particularly regarding how intermolecular interaction forces dictate assembly dynamics, drug release, and therapeutic tradeoffs. To address this issue, we constructed two docetaxel-based prodrug nanoassemblies with diverse modification modules: oleic acid (OA, C18:1 fatty acid) and oleyl alcohol (OAL, C18:1 fatty alcohol), respectively. This approach revealed three key structure-performance relationships: (i) modification modules modulate the type and strength of intermolecular forces within prodrug systems; (ii) intermolecular forces regulate the assembly compactness and stability of nanoassemblies; and (iii) the resulting drug release and pharmacokinetic behavior govern the therapeutic efficacy-to-safety equilibrium. The results demonstrated that OA NAs achieved superior drug release and antitumor efficacy yet faced limitations in nanostructural compactness and biosafety. Conversely, OAL NAs, with reduced oxidative sensitivity, offered a more compact nanostructure, prolonged stability, and improved biosafety in vivo . These findings provided essential structure-performance insights to guide the rational design of prodrug nanoassemblies.
研究领域:
纳米医学
·
药物化学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Li-Jing Lan,Lian-Bing Long,Ling-Zhi Shi,Ming-Wei Huo,Xiang-Xiang Huang,Ya-Wen Liu,Le-Yan Gu,Jing-Yi Liu,Ye-Chao Zhang,Renyu Huang,Qing-Ri Cao
The industrial scalability and clinical translation of liposomal formulations are significantly hindered by challenges in stability and batch-to-batch variability. To address these limitations, docetaxel (DTX)-loaded long-circulating liposomal freeze-dried powders were engineered via a synergistic integration of microfluidic technology and lyophilization, optimized through an orthogonal experimental design focusing on particle size, polydispersity index (PDI), and entrapment efficiency (EE). The optimized formulation, incorporating hydroxypropyl-β-cyclodextrin (HP-β-CD) as a lyoprotectant, demonstrated nanoscale particle diameter (∼120 nm), monodisperse distribution (PDI < 0.2), and elevated EE (>90 %), with physicochemical integrity preserved post-lyophilization. Reconstituted DTX liposomes (DTX-Lip) exhibited pH-dependent sustained release kinetics, with enhanced drug elution at acidic pH (5.5) versus physiological pH (7.4). Solid-state characterization (XRD, FT-IR, DSC) confirmed molecular interactions between DTX and lipid-excipient matrices. In vitro cytotoxicity assays revealed superior apoptotic induction in A549 human lung carcinoma cells by DTX-Lip compared to free DTX solution (DTX-Sol). Pharmacokinetic profiling in vivo demonstrated prolonged systemic circulation of DTX-Lip, marked by significantly elevated area under the curve (AUC 0-∞ ), maximum drug concentration (C max ), mean retention time (MRT 0-∞ ), longer half-life (T 1/2 ), lower clearance (CL) and steady-state volume of distribution (V ss ) relative to DTX-Sol (p < 0.05). In a C57BL/6 murine lung cancer model, DTX-Lip elicited significant tumor suppression (p < 0.05) without mortality, underscoring enhanced therapeutic efficacy and mitigated systemic toxicity. Collectively, the engineered DTX-Lip system combines optimal nano-pharmaceutical attributes (size, homogeneity, EE), controlled release, and favorable in vitro-in vivo performance, offering a robust platform for industrial-scale production of stable, efficacious liposomal DTX formulations. These findings advance translational strategies for liposome-based chemotherapeutics with improved reproducibility and clinical safety.
研究领域:
肿瘤学
·
药剂学
·
纳米医学
·
药物递送
·
药代动力学
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转化医学
·
临床药理学
✓ 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）