MOLECULAR PHARMACEUTICS
·
2017
·
IF 4.44
Bing Deng,Mengxin Xia,Jin Qian,Rui Li,Lujia Li,Jianliang Shen,Guowen Li,Yan Xie
For addressing the dilemma of in vivo stability and antitumor effects of micellar drugs, novel organic and inorganic hybridized nanoparticle, that is, hyaluronic acid-mineralized micelles, are designed to efficiently deliver paclitaxel (PTX). The resulting micelles exhibit excellent drug loading (30.6%) and entrapment efficiency (87.8%) for PTX with a small size (134.8 nm). Notably, the dual-sensitive release of PTX-loaded mineralized micelles is obtained in the conditions of 40 mM GSH and pH 5.0, whereas release is slow in the physiological environment. With favorable cell uptake, mineralized micelles show decent tumor accumulation, which corresponds to their significant targeting capacity from the observed real-time images. Compared with Taxol, PTX-loaded mineralized micelles show a lower half-maximal inhibitory concentration value (0.025 μg/mL), higher cell apoptosis rate (23.5%) in MDA-MB-231 cells, lower systemic toxicity to nude mice, and more potent in vivo tumor inhibition (1.57-times higher than that of Taxol (p < 0.05)).
研究领域:
药剂学
·
肿瘤学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2015
·
IF 6.025
Yajie Gao,Yanxia Zhou,Lei Zhao,Chao Zhang,Yushu Li,Jinwen Li,Xinru Li,Yan Liu
Cyclic RGDyK (cRGDyK)-conjugated pH-sensitive polymeric micelles were fabricated for targeted delivery of paclitaxel to prostate cancer cells based on pH-sensitive copolymer poly(2-ethyl-2-oxazoline)-poly( d , l -lactide) (PEOz-PLA) and cRGDyK-PEOz-PLA to enhance antitumor efficacy. The prepared micelles with an average diameter of about 28 nm exhibited rapid release behavior at endo/lysosome pH, effectively enhanced the cytotoxicity of paclitaxel to PC-3 cells by increasing the cellular uptake, which was correlated with integrin α v β 3 expression in tumor cells. The active targeting activity of the micelles was further confirmed by in vivo real time near-infrared fluorescence imaging in PC-3 tumor-bearing nude mice . Moreover, the active targeting and pH-sensitivity endowed cRGDyK-conjugated micelles with a higher antitumor effect in PC-3 xenograft-bearing nude mice compared with unmodified micelles and Taxol with negligible systemic toxicity. Therefore, these results suggested that cRGDyK-conjugated pH-sensitive polymeric micelles may be a promising delivery system for efficient delivery of anticancer drugs to treat integrin α v β 3 -rich prostate cancers.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
DOI
PubMed
高影响因子
Cell Death Discovery
·
2023
·Vol. 9
·期 1
·1-11
·
IF 7
Zhang Libo,Ren Zhen,Lü Jinhui,Mo Xinhai,Lin Jie,Li Ya,Ma Wenjing,Liu Pengfei,Shen Yajing,Zhao Qian,Qian Lu,Cheng Xiaoxin,Yu Zuoren,Zhang Bo
Nanomaterials have been well demonstrated to have the potential to be used for tumor cell-targeted drug delivery. Targeted inhibition of miR-221 was proved to promote the sensitivity of triple genitive breast cancer (TNBC) cells to chemo-drugs. In order to improve the chemotherapeutic effect in TNBC, herein, we developed a novel kind of nanoparticles shelled with PLGA and loaded with perfluoropentane (PFP), paclitaxel (PTX), and anti-miR-221 inhibitor, which was named PANP. Ultrasound-triggered vaporization of PFP in PANPs was utilized for real-time imaging track of the nanoparticles in vivo. In addition, macrophages were applied for the internalization of PANPs to form RAW-PANP with strong chemotaxis to accumulate around cancer cells. Nanoparticles with different contents did not cause M2 polarization compared with the control group but caused polarization toward M1. We compared the inherent tumor-homing behavior of macrophages containing different contents with that of normal macrophages and no significant abnormalities were observed. After injection into the tumor-burden mice, RAW-PANPs showed enrichment within tumor tissues. Upon the ultrasound cavitation-triggered burst, PTX was released in the tumor. Meanwhile, the release of anti-miR-221 improved the sensitivity of tumor cells to PTX. As a result, RAW-PANPs showed high efficiency in suppressing TNBC cell proliferation in vitro and inhibiting tumor growth and progression in vivo. The treatments did not induce liver, heart, or kidney injury. In conclusion, the current study not only developed a macrophage-carried, ultrasound-triggered, cancer cell-targeted chemotherapeutic system, but also demonstrated a miRNA-based technique to promote drug sensitivity of cancer cells, which holds strong potential to treat patients with TNBC, especially for those suffering drug-resistance. The innovation of this study is to use macrophages to deliver nanoparticles to the tumors and then use ultrasound locally to burst the nanoparticles to release the miRNA and PTX.
研究领域:
癌症生物学
·
药学
·
生物医学工程
·
纳米技术
·
治疗诊断学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2015
·
IF 3.65
Nan Zhang,Xuefan Xu,Xue Zhang,Ding Qu,Lingjing Xue,Ran Mo,Can Zhang
Development of combination photothermal–chemotherapy platform is of great interest for enhancing antitumor efficacy and inhibiting tumor recurrence , which supports selective and dose-controlled delivery of heat and anticancer drugs to tumor. Here, an injectable nanocomposite hydrogel incorporating PEGylated gold nanorods (GNRs) and paclitaxel-loaded chitosan polymeric micelles (PTX-M) is developed in pursuit of improved local tumor control. After intratumoral injection, both GNRs and PTX-M can be simultaneously delivered and immobilized in the tumor tissue by the thermo-sensitive hydrogel matrix. Exposure to the laser irradiation induces the GNR-mediated photothermal damage confined to the tumor with sparing the surrounding normal tissue. Synergistically, the co-delivered PTX-M shows prolonged tumor retention with the sustained release of anticancer drug to efficiently kill the residual tumor cells that evade the photothermal ablation due to the heterogeneous heating in the tumor region. This combination photothermal–chemotherapy presents superior effects on suppressing the tumor recurrence and prolonging the survival in the Heps-bearing mice, compared to the photothermal therapy alone.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2021
·
IF 3.981
Guanglan Ma,Xiao Du,Jianping Zhu,Feng Xu,Hua Yu,Juan Li
Liver cancer is one of the leading causes of cancer mortality worldwide. In this study, poly(lactide) (PLA) and hyaluronic acid (HA) co-modified half-generation of PAMAM G4.5 dendrimers (sPA) was chosen as the intelligent carrier for co-delivery of paclitaxel (PTX) and sorafenib (SOR) to treat liver cancer. The multifunctional micelle (HA-PALA@PTX + SOR) possessed a uniform size of 152.6 nm, good stability against serum medium, and a rapid in vitro drug release behavior under acidic condition in the presence of HAase. Cellular uptake study demonstrated an efficient intracellular delivery and drug accumulation in HepG2 cells. The antitumor and anti-metastasis efficacy of functionalized micelle was more obvious than that of free drugs. These data provided strong evidence that HA-PALA@PTX + SOR micelle could be utilized as a biocompatible and tumor targeted nano-carrier for the delivery of multiple anticancer drugs in liver cancer treatment.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2013
·
IF 1.7
Longlong Chang,Weiwei Wang,Pingsheng Huang,Zesheng Lv,Fuqiang Hu,Jianhua Zhang,Deling Kong,Liandong Deng,Anjie Dong
Novel biodegradable core-crosslinked nanoparticles (CNPs) consisting of methoxy poly(ethylene glycol)-block-poly(ϵ-caprolactone-co-γ-cinnamoyloxy-ϵ-caprolactone) (mPEG-b-P(CL-co-CCL)) were prepared and evaluated for paclitaxel (PTX) delivery. mPEG113-b-P(CL65.2-co-CCL10.1) had a higher drug loading efficiency (95%) compared to mPEG113-b-PCL93.1 (43%). The stability of NPs has been largely improved and PTX release was significantly inhibited by crosslinking via UV irradiation at λ = 254 nm. MTT assays demonstrated that both blank non-crosslinked and crosslinked NPs showed low cytotoxicity to NCL-H460 cells while PTX-loaded non-crosslinked and crosslinked NPs exhibited obvious cytotoxicity against NCL-H460 cells, and the cytotoxicity was both dose-dependent and time-dependent. Furthermore, after 48 h incubation the cell viability of PTX-loaded crosslinked NPs was lower compared to that of PTX-loaded non-crosslinked NPs or free PTX. These properties indicated that CNPs prepared from mPEG-b-P(CL-co-CCL) have great potentials as carriers for drug delivery.
研究领域:
药物递送
·
纳米医学
·
高分子化学
·
生物材料
·
药剂学
✓ 已验证
DOI
高影响因子
Journal of Pharmaceutical Investigation
·
2025
·
IF 5.1
Chen Yali,Qian Lei,Xu Chunyun,Huo Hongjie,Sun Zhenya,Zhang Hongyang,Yuan Shuang,Qi Yan,Chu Peng,Chen Lixue,Ding Yanfang,Li Lei
Purpose One of the hallmarks of cancer cells is their elevated levels of reactive oxygen species (ROS) compared with normal cells. Capitalizing on this, a novel paclitaxel (PTX, a first-line chemotherapeutic agent) prodrug was designed and synthesized by attaching a cinnamaldehyde (CA) molecule to PTX via a ROS-responsive thioacetal group. Methods The paclitaxel prodrug (PTX-S-CA) prodrug was synthesized and characterized, followed by self-assembly into nanoparticles (NPs) using DSPE-PEG 2K as a stabilizer, forming PTX-S-CA/DSPE-PEG 2K NPs. The physicochemical properties of the NPs were evaluated, which included drug-loading capacity, encapsulation efficiency, and plasma stability. In vitro cytotoxicity assays were conducted on cancer cells, and in vivo anti-tumor efficacy was assessed in a murine tumor model. The pharmacokinetics of the NPs were also studied in rats. Results In the tumor microenvironment, the ROS-sensitive thioacetal group in PTX-S-CA was degraded due to high ROS levels, leading to the release of both PTX and CA. The released CA synergistically enhanced the anti-tumor effects of PTX by inducing additional ROS production within the mitochondria. The NPs demonstrated a high loading capacity and encapsulation efficiency for PTX-S-CA, high cytotoxicity against cancer cells, excellent anti-tumor effects on mice, and high plasma stability in rats. Conclusion The use of the NP drug delivery platform served as a potentially effective therapeutic strategy for treating tumors, especially breast cancer.
研究领域:
肿瘤学
·
药剂学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
ANTICANCER RESEARCH
·
2018
·Vol. 38
·期 1
·219-225
·
IF 1.865
CAIYUN DENG,CHANG XU,XIAOMIN ZHANG,JU YAO,YINGXIN ZHANG,BO YU,ROBERT J. LEE,CHENGJUN JIANG
Background/Aim: Polymeric micelles are promising vehicles for paclitaxel delivery. Further improvement in the stability of the micelle formulation is desirable. Materials and Methods: Monomethoxy poly(ethylene glycol)-block-poly(D,L-lactide)-9-fluorenylmethoxycarbonyl-L-phenylalanine (mPEG-PDLLA-Phe(Fmoc)) was synthesized through a classical esterification reaction. Paclitaxel-loaded mPEG-PDLLA-Phe(Fmoc) micelles (PTX-PheMs) were prepared by the self-assembly method. Composition, structure and physicochemical properties were characterized. Pharmacokinetics were evaluated in rats. Therapeutic effect was evaluated in tumor-bearing mice. Safety profile was assessed by a hemolysis assay and an acute-toxicity study. Results: The average size of PTX-PheMs was about 45 nm. The hemolysis and acute-toxicity tests confirmed its biocompatibility and safety. The pharmacokinetics and therapeutic effect experiments demonstrated its long circulation property and superior antitumor effect. Conclusion: mPEG-PDLLA-Phe(Fmoc) micelle is a biocompatible and effective drug delivery system for hydrophobic drugs such as PTX.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Menglan Wang,Lewei Li,Lifang Tang,Zuowei Xiao,Hong Yang,Qian Luo,Shiyang Fu,Zehui Fan,Xiaojun Tao,Chunlian He,Xiong Wu
Chemoresistance remains a major barrier to the effective treatment of triple-negative breast cancer (TNBC). To enhance the targeting and chemosensitivity of paclitaxel (PTX) for TNBC treatment, we developed a dual-drug-loaded nanodelivery system (BBR@PTX NPs) using BI-PEG-PTX polymer as the carrier, with berberine (BBR) loaded at an optimal ratio (PTX:BBR =1:10) determined by synergistic toxicity assays. The BBR@PTX NPs in this study demonstrated loading efficiencies of 9.5% for PTX and 28.06% for BBR, with an average particle size of 130-150 nm and a uniform distribution. In in vitro cellular assays, BBR potentiates PTX, achieving synergistic anti-tumor efficacy. The BBR@PTX NP co-delivery system enhances bioavailability by evading macrophage phagocytosis and lysosomal capture. The ability to inhibit cell growth, metastasis, and induce apoptosis was significantly enhanced after the NPs were taken up by tumor cells. In vivo experiments demonstrated that the BBR@PTX NP nanomicellar system enhanced tumor targeting, anti-tumor activity, and biosafety compared to single-agent formulations. These findings establish an effective approach to develop high-performance, selective, and low-toxicity nanocellular aggregates for combined therapy of solid triple-negative breast cancer.
研究领域:
肿瘤学
·
药剂学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Hao Zhang,Chengyuan Xing,Binyuan Yan,Hanqi Lei,Yupeng Guan,Shiqiang Zhang,Yang Kang,Jun Pang
Combination therapy has emerged as a promising approach for treating tumors, although there is room for improvement. This study introduced a novel strategy that combined the enhancement of apoptosis, ferroptosis, and DNA damage to improve therapeutic outcomes for prostate cancer. Specifically, we have developed a supramolecular oxidative stress nanoamplifier, which was comprised of β-cyclodextrin, paclitaxel, and ferrocene-poly(ethylene glycol). Paclitaxel within the system disrupted microtubule dynamics, inducing G2/M phase arrest and apoptosis. Concurrently, ferrocene utilized hydrogen peroxide to generate toxic hydroxyl radicals in cells through the Fenton reaction, triggering a cascade of reactive oxygen species expansion, reduction of glutathione levels, lipid peroxidation, and ferroptosis. The increased number of hydroxyl radicals and the inhibitory effect of THZ531 on DNA repair mechanisms exacerbated DNA damage within tumor cells. As expected, the supramolecular nanoparticles demonstrated excellent drug delivery ability to tumor cells or tissues, exhibited favorable biological safety in vivo, and enhanced the killing effect on prostate cancer.
研究领域:
药理学
·
肿瘤学
·
纳米医学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Mingming Zhang,Xi Zhang,Sijun Huang,Yueming Cao,Yi Guo,Li Xu
Paclitaxel (PTX) is commonly used in clinical tumor therapy. However, chemoresistance and the inducement of tumor metastasis severely affect the efficacy of PTX. To develop a treatment strategy to reverse chemoresistance, the co-delivery of PTX and small interfering RNA with nanocarriers were programmed in this study. The carrier we have programmed exhibits excellent safety, stability, and delivery efficiency for co-delivery of siRNA and PTX. After rapid release of siRNA, PTX could be released within 72 h. The siBcl-xL and siMcl-1 inhibited cell migration decreased the mitochondrial membrane potential , and induced the release of reactive oxygen species while synergistically functioning with the antineoplastic effects of PTX. Our strategy reduced IC 50 values by 2–5-fold in different cell lines, and the results of flow cytometry confirmed increased apoptosis rates and effectively inhibited cell migration. Synergistic therapy effectively reversed chemoresistance in PTX-resistant breast cancer cells. Similarly, the synergistic administration strategy showed significant sensitizing effects in vivo. Our study demonstrates the combined application of multiple synergistic antitumor administration strategies.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Central Science
·
2024
·
IF 12.7
Yaqi Li,Yixin Sun,Qing Wang,Shuo Wang,Cuiyun Liu,Yuetong Huang,Wenxin Zhong,Xiyan Wang,Wenjing Wang,Shiyi Zuo,Xianbao Shi,Xiaohui Pu,Jin Sun,Zhonggui He,Bingjun Sun
Prodrug-based nanoassemblies are promising platforms for cancer therapy. Prodrugs typically consist of three main components: drug modules, intelligent response modules, and modification modules. However, the available modification modules are usually hydrophobic aliphatic side chains, which affect the activation efficiency of the prodrugs. Herein, hydrophilic ethylene glycol fragments were inserted between the modification modules and the response modules, and the important effects of hydrophilic fragments on the assembly, drug release, and therapeutic index of the prodrugs were investigated. Notably, the introduction of hydrophilic fragments affected the intermolecular forces of the prodrugs and increased the interaction of hydrogen bonding. In addition, hydrophilic fragments significantly improved the redox drug release profiles, which affected the therapeutic index of the prodrug nanoassemblies. PTX-SS-OA NPs with hydrophilic fragments exhibited increased redox sensitivity, enhanced cytotoxicity, and superior antitumor efficacy. In comparison, PTX-SS-OAL NPs without hydrophilic fragments showed limited redox sensitivity and cytotoxicity but displayed better safety. Overall, the hydrophilic fragment is a critical determinant in modulating the therapeutic index of the prodrug nanoassemblies, which contributes to the development of advanced prodrug nanodelivery systems.
研究领域:
药学
·
纳米技术
·
癌症治疗
·
药物递送系统
✓ 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）