International Journal of Nanomedicine
·
2022
·
IF 7.033
Yumeng Wei,Mingtang Zeng,Chao Pi,Hongping Shen,Jiyuan Yuan,Ying Zuo,Jie Wen,Pu Guo,Wenmei Zhao,Ke Li,Zhilian Su,Xinjie Song,Shaozhi Fu,Robert J Lee,Ling Zhao
Purpose Paclitaxel (PTX) has been widely utilized for the treatment of breast cancer. However, drawbacks, such as poor aqueous solubility, rapid blood clearance and severe toxicity, greatly reduce its efficacy and safety. Herein, a novel self-developed curcumin derivative (CUD) was chosen as the carrier to develop a long-acting PTX nano-delivery system (PTX-Sln@CUD) in order to improve its pharmacokinetic behavior, anti-breast cancer efficacy and safety. Methods PTX-Sln@CUD was prepared using solid dispersion and ultrasonic technology. Relevant physical and chemical properties, including stability and release behavior, were characterized. The clearance of PTX-Sln@CUD in vivo was studied by pharmacokinetic experiments. The anti-tumor activity of PTX-Sln@CUD was investigated in vitro and in vivo. Hemolysis experiments, acute toxicity and cumulative toxicity studies were performed in mice to determine the safety of PTX-Sln@CUD. Results The average particle size, PDI, Zeta potential, encapsulation efficiency and loading efficiency of the PTX-Sln@CUD were 238.5 ± 4.79 nm, 0.225 ± 0.011, −33.8 ± 1.26 mV, 94.20 ± 0.49% and 10.98 ± 0.31%, respectively. PTX-Sln@CUD was found to be stable at room temperature for half a year. The cumulative release rates of PTX-Sln@CUD at 24, 96 and 168 h were 17.98 ± 2.60, 57.09 ± 2.32 and 72.66 ± 4.16%, respectively, which were adherent to zero-order kinetics. T 1/2 , MRT (0-t) and AUC (0-t) of the PTX-Sln@CUD group were 4.03-fold (44.293 h), 7.78-fold (38.444 h) and 6.18-fold (14.716 mg/L*h) of the PTX group, respectively. PTX-Sln@CUD group demonstrated stronger anti-breast cancer activity than the PTX group. Importantly, the PTX-Sln@CUD group was safer compared to the PTX group both in vitro and in vivo. Conclusion PTX-Sln@CUD was verified as promising therapeutic nanoparticles for breast cancer and provided a novel strategy to solve the problem of low efficacy and poor safety of clinical chemotherapy drugs.
研究领域:
药理学
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Danping Wang,Shengyao Xu,Si Zheng,Rong Chai,Zhiyu Kuang,Yixin Sun,Yaqi Li,Shiyi Zuo,Xiang Gao,Xin Li,Qikun Jiang,Zhonggui He,Jin Sun,Hongrui Lei,Anhua Wang,Bingjun Sun
Paclitaxel (PTX) is an effective agent against a wide spectrum of solid tumors. Lipusu is the first and only marketed liposomal PTX product in the world. However, it is hindered by the insufficient affinity between PTX and phospholipids, resulted in a low drug loading (≈5.68%), poor stability, and limited antitumor efficacy. Inspired by the structural characteristics of phospholipids, a phospholipid-like PTX prodrug (PTX-OCT) is designed to construct prodrug liposomes (PTX-OCT PLs). Compared with Lipusu, PTX-OCT PLs possessed a smaller particle size (135 vs 400 nm) with a higher drug loading (10.52% vs 5.68%, equal to PTX). Meanwhile, PTX-OCT PLs would deliver PTX efficiently in vivo evidenced by the AUC higher than Lipusu (≈170-fold) due to their superior stability. The introduction of disulfide bonds endowed PTX-OCT PLs with the capacity of intelligent activation, which is the key element for tumor selectivity. With such characterizations, PTX-OCT PLs exhibited potent antitumor efficacy with good tolerance in 4T1-bearing model, even better than Abraxane and Lipusu. To summarize, this work designed PTX nanomedicines with potential market competitiveness and enriched the theoretical basis of designing advanced nanomedicines for efficient cancer treatment.
研究领域:
药剂学
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纳米技术
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肿瘤学
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药物化学
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药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Ling Chen,Meng Hu,Hui-min Yan,Xue-Qing Ding,Qiu-xiang Yang,Ling Wang,Hong Pan
The immunosuppressive microenvironment and impaired antigen presentation represent significant challenges in melanoma treatment. This study explores strategies to overcome these barriers by simultaneously inducing tumor cell immunogenic cell death (ICD) and enhancing antigen presentation. We developed hyaluronic acid/R8-RGD dual-modified albumin nanoparticles (HR/LDPP-NPs) designed to co-deliver low-dose paclitaxel (PTX) and the PCSK9 inhibitor PF-06446846. PTX induces ICD, releasing calreticulin (CRT), ATP, and HMGB1 danger signals, thereby transforming tumor cells into an in situ antigen source and initiating dendritic cell-mediated T-cell responses, akin to an intrinsic vaccine effect. Simultaneously, the inhibition of PCSK9 significantly upregulates tumor MHC-I expression, counteracting immune evasion. This synergistic approach, combining in situ vaccination with enhanced antigen presentation, significantly amplifies antitumor immunity. Both in vitro and in vivo experiments demonstrate that these spatiotemporally coordinated dual-targeting nanoparticles achieve substantial therapeutic efficacy with significantly reduced toxicity, presenting a novel chemo-immunotherapeutic strategy for melanoma treatment.
研究领域:
肿瘤学
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免疫学
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纳米医学
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转化医学
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分子药理学
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肿瘤免疫治疗
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2025
·Vol. 18
·期 11
·1699
·
IF 4.8
Zheng Ye,Chao Hong,Min Jiang,Wenkui Zou,Yaning Ren,Mingfang Li,Xinyue Xue,Xiaoting Xie,Tong Zhang,Yue Ding
Background/Objectives: Breast cancer is the most prevalent malignancy among women, and paclitaxel (PTX) is a first-line chemotherapeutic, but chemoresistance driven by ATP-binding cassette (ABC) transporters limits its efficacy. Single-target ABC inhibitors fail due to toxicity and cooperative transporter activity, creating an urgent need for safe multi-target strategies. Membrane cholesterol-rich lipid rafts support ABC transporter function, making cholesterol a key chemoresistance target. This study explored a cholesterol-targeted approach for overcoming PTX resistance.Methods: A PTX-resistant breast cancer line (MCF-7/PTX) showing ABCB1/ABCC3 co-upregulation and enriched cholesterol rafts was established. The effects of Polyphyllin H (PPH), a steroidal saponin fromParis polyphylla, were compared with lovastatin, a biosynthetic cholesterol inhibitor. In vitro and in vivo assays investigated Polyphyllin H’s cholesterol binding and effects on transporters, PTX accumulation, and tumor growth.Results: PPH directly binds membrane cholesterol, disrupting lipid rafts, downregulating ABCB1/ABCC3, reducing drug efflux, and increasing intracellular PTX to restore sensitivity. PPH showed superior cholesterol-binding and resistance-reversal efficacy than lovastatin, with faster, stronger PTX-enhanced cytotoxicity and tumor suppression.Conclusions: PPH reverses PTX resistance by targeting cholesterol-lipid rafts to inhibit multiple ABC transporters. This offers a safer adjuvant for PTX-based breast cancer therapy and a translational framework for other drug-resistant malignancies.
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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癌症研究
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天然产物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 17
·3111-3121
·
IF 4.543
Yan-Ling Luo,Xue-Yin Zhang,Yuan Wang,Fang-Jie Han,Feng Xu,Ya-Shao Chen
pH-Sensitive H-type multiblock copolymers, namely, poly(methacrylic acid)2-block-epoxidized hydroxyl-terminated polybutadiene-block-poly(methacrylic acid)2 (PMAA2-b-epoHTPB-b-PMAA2), were synthesized by atom-transfer radical polymerization and subsequent in situ epoxidation by peracetic acid and characterized by 1H NMR, FT-IR and SEC techniques. The impact of epoxidation on the physicochemical and biomedical properties of copolymer self-assembly micelle nanoparticles was investigated by fluorescence spectrometry, DLS, TEM and an MTT assay. The experimental results indicated that epoxidation resulted in the formation of more stable copolymer micelle nanoparticles with a lower critical micelle concentration, smaller micelle size, and higher loading capacity and encapsulation efficiency of drugs than those without epoxidation. In particular, epoxidized copolymer micelle nanoparticles exhibited reasonable pH sensitivity at a pH of 5.3–5.6. The hydrophobic anticancer drug paclitaxel (PTX) displayed faster release rates from epoxidized nanomicelles than from unepoxidized nanomicelles in a PBS solution of a pH of 4.8–6.6, whereas in PBS of a pH of 7.4 smaller amounts of PTX were released from epoxidized nanomicelles than from unepoxidized nanomicelles. Epoxidized copolymer nanomicelles were reasonably biodegradable after the drug was released, and their degradation rate was faster than that of their unepoxidized counterparts. An MTT assay was performed to determine the biocompatibility of epoxidized copolymer micelle nanoparticles and the anticancer activities of PTX-loaded nanomicelles, which were important for applications in the therapy of cancers as a controlled-release drug carrier.
研究领域:
材料科学
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药物递送
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2014
·
IF 4.787
Yuling Bao,Yuanyuan Guo,Xiangting Zhuang,Dan Li,Bolin Cheng,Songwei Tan,Zhiping Zhang
To overcome the multidrug resistance (MDR) of P-glycoprotein (P-gp) substrate anticancer drugs, such as paclitaxel (PTX), a novel dual-functional prodrug, D-α-tocopherol polyethylene glycol succinate (TPGS) based PTX prodrug (TPGS-S-S-PTX), was synthesized here to fulfill the synergistic effect of P-gp inhibiting and intracellular redox-sensitive release. The prodrug could self-assemble into stable micelles in physiological environment with a diameter of ∼140 nm, while it disassociated in reductive condition and released PTX and TPGS active derivatives rapidly. High cell cytotoxicity in PTX-resistant human ovarian cell line A2780/T was observed with enhanced PTX accumulation due to the P-gp inhibition by the TPGS moiety. The IC50 of TPGS-S-S-PTX was 55% and 91% more effective than that of Taxol (clinical formulation of PTX) and uncleavable TPGS-C-C-PTX prodrug, respectively. This was found to be related with the increased apoptosis/necrosis and cell arrest in G2/M phase. In vivo evaluation of the TPGS-S-S-PTX prodrug exhibited an extended half-life, increased AUC (area under the concentration–time curve), enhanced tumor distribution and significant tumor growth inhibition with reduced side effects as compared to Taxol and TPGS-C-C-PTX. This prodrug has great potential in improving efficiency in the treatment of MDR tumors.
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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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2017
·Vol. 9
·期 35
·13142-13152
·
IF 7.367
Jingxin Mo,Li Wang,Xiaojia Huang,Bing Lu,Changye Zou,Lili Wei,Junjun Chu,Paul K. Eggers,Shen Chen,Colin L. Raston,Jun Wu,Lee Yong Lim,Wei Zhao
Ovarian cancer (OC) is the most lethal gynecologic cancer. Survival statistics have show no significant developments over the last three decades, highlighting the fact that current therapeutic strategies require substantial improvements. In this study, we designed a novel folic acid-PEG-conjugated p-phosphonated calix[4]arene nanoparticle (Fp-PCN) for the simultaneous delivery of paclitaxel (PAC) and carboplatin (CAR) at an optimal ratio (5 : 1, mol : mol) to utilize their potential synergistic effect against OC cells. The Fp-PCNs loaded with PAC and CAR (Fp-PCNPAC+CAR) resulted in a remarkable efficacy in the suppression of OC, both in vitro and in vivo. Compared to free drugs, Fp-PCNPAC+CAR showed stronger apoptosis induction as well as invasion and self-renewal capacity suppression in SKOV-3 cells. The molecular mechanism to address the synergism is that Fp-PCNPAC+CAR downregulated JMJD3 expression to modulate the H3K27me3 epigenetic mark of the promoters of HER2 and MYCN. Furthermore, the expressions of JMJD3 and HER2 were significantly associated with poor outcomes for ovarian patients. Our study demonstrates that co-delivery of PAC and CAR can be achieved with the Fp-PCNs, and reveals a previously unrecognized and unexpected role of the JMJD3-HER2 signaling axis in PAC and CAR treatment of OC.
研究领域:
肿瘤学
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药学
·
纳米技术
·
分子生物学
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Juan Du,Lanlan Zong,Mengmeng Li,Keke Yu,Yonghui Qiao,Qi Yuan,Xiaohui Pu
Introduction Cancerous tumors are still a major disease that threatens human life, with tumor multidrug resistance (MDR) being one of the main reasons for the failure of chemotherapy. Thus, reversing tumor MDR has become a research focus of medical scientists. Methods Here, a reduction-sensitive polymer prodrug micelle, mPEG-DCA-SS-PTX (PDSP), was manufactured with a new polymer inhibitor of drug resistance as a carrier to overcome MDR and improve the anti-tumor effect of PTX. Results The PDSP micelles display good stability, double-responsive drug release, and excellent biocompatibility. The PDSP micelles reduced the cytotoxicity of PTX to normal HL-7702 cells and enhanced that to SMMC-7721 and MCF-7 cells in vitro. Improved sensitivity of A549/ADR to PDSP was also observed in vitro. Furthermore, in vivo experiments show reduced systemic toxicity and enhanced therapeutic efficacy of PTX to H22 subcutaneous tumor-bearing mice. Conclusion This work proves that the reduction-sensitive polymer prodrug micelles carried by the new polymer inhibitor can be used as an alternative delivery system to target tumors and reverse MDR for paclitaxel and other tumor-resistant drugs.
研究领域:
药理学
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肿瘤学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2016
·
IF 6.008
Jiulong Zhang,Xiufeng Zhao,Qing Chen,Xiaoyi Yin,Xiu Xin,Kexin Li,Mingxi Qiao,Haiyang Hu,Dawei Chen,Xiuli Zhao
Multidrug resistance (MDR) of tumor cells is becoming the main reason for the failure of chemotherapy and P-glycoprotein (P-gp) mediated drug efflux has demonstrated to be the key factor for MDR. To address this issue, a novel pH-responsive mixed micelles drug delivery system composed of dextran-g-poly(lactide-co-glycolide)-g-histidine (HDP) and folate acid-D-α-tocopheryl polyethylene glycol 2000 (FA-TPGS2K) copolymers has been designed for the delivery of antitumor agent, paclitaxel (PTX) via FA-receptor mediated cell endocytosis , into PTX-resistant breast cancer MCF-7 cells (MCF-7/PTX). PTX-loaded FA-TPGS2K/HDP mixed micelles were characterized to have a small size distribution, high loading content and excellent pH-responsive drug release profiles. Compared with HDP micelles, FA-TPGS2K/HDP mixed micelles showed a higher cytotoxicity against MCF-7 and MCF-7/PTX cells due to the synergistic effect of FA-receptor mediated cell endocytosis, pH-responsive drug release and TPGS mediated P-gp inhibition. P-gp expression level, ATP content and mitochondrial membrane potential change have been measured, the results indicated blank FA-TPGS2K/HDP mixed micelles could inhibit the P-gp activity by reducing the mitochondrial membrane potential and depleting ATP content but not down-regulating the P-gp expression. In vivo antitumor activities demonstrated FA-TPGS2K/HDP mixed micelles could reach higher antitumor activity compared with HDP micelles for MCF-7/PTX tumor cells. Histological assay also indicated that FA-TPGS2K/HDP mixed micelles showed strongly apoptosis inducing effect, anti-proliferation effect and anti-angiogenesis effect. All these evidences demonstrated this pH-sensitive FA-TPGS2K/HDP micelle-based drug delivery system is a promising approach for overcoming MDR. Statement of Significance In this work, a novel FA-TPGS2K copolymer has been synthesized and used it to construct mixed micelles with HDP copolymer to overcome MDR effect. Furthermore, a series in vitro and in vivo evaluations have been made, which supported enough evidences for the efficient delivery of antitumor drug to MDR cells.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
药物递送系统
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2021
·
IF 8.947
Kaipei Luo,Yi Gao,Shaoping Yin,Yawen Yao,Hua Yu,Guangji Wang,Juan Li
Metastasis is one of the major causes of mortality in patients suffering from breast cancer. The signal transducer and activator of transcription 3 (STAT3) is closely related to cancer metastasis. Herein, a multifunctional nanocomplex was developed to simultaneously deliver paclitaxel (PTX) and STAT3 siRNA (siSTAT3) to inhibit tumor growth and prevent metastasis of breast cancer cells. PTX was encapsulated into the synthesized polyethyleneimine-polylactic acid-lipoic acid (PPL) micelle through hydrophobic interaction, while siSTAT3 was condensed onto polyethyleneimine through electrostatic interaction . The surface charge of the drug-loaded nanocomplex ( siSTAT3 PPL PTX ) was then converted to negative by coating with hyaluronic acid (HA). The multifunctional nanocomplex (HA/ siSTAT3 PPL PTX ) effectively entered CD44-overexpressed 4T1 cells via an active targeting mechanism. HA shell was degraded by the concentrated hyaluronidase in the endo/lysosome and the rapid drug release was triggered by the redox micro-environment of cytoplasm. Moreover, HA/ siSTAT3 PPL PTX showed enhanced cytotoxicity against tumor cells due to a synergistic effect of PTX and siSTAT3. The effective inhibition of tumor metastasis was confirmed by in vitro cell migration and invasion in 4T1 cells. More importantly, a superior antitumor efficacy was observed in orthotopic 4T1 tumor-bearing mice, with no side effects in major organs, and the lung metastasis was strongly inhibited in 4T1 metastasis model. In conclusion, the multifunctional nanocomplex provides a versatile platform for efficient treatment of metastatic cancer through tumor-targeted chemo-gene combined therapy. Statement of significance Metastasis is one of the major causes of mortality in patients suffering from breast cancer. The signal transducer and activator of transcription 3 (STAT3) is closely related to cancer metastasis. In this study, a multifunctional nanocomplex co-loaded with paclitaxel (PTX) and STAT3 siRNA was constructed and characterized. The co-delivery system exhibited active tumor targeting, effective endo/lysosomal escape, and rapid intracellular drug release. Both in vitro and in vivo studies indicated that the nanocomplex could lead to superior tumor growth inhibition, as well as metastasis suppression by silencing expression of STAT3 and p-STAT3. This present study implies that the nanocomplex could be a potential platform for targeted treatment of metastatic cancer through chemo-gene combined therapy.
研究领域:
癌症研究
·
纳米技术
·
药学
·
分子生物学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2026
·
IF 8.7
Xiaoling Guo,Lina Zhou,Anya Buerliesi,Jiahui Ye,Yinhua Lv,Wenqian Wei,Jinlan Jiao,Weihong Ge,Yun Zhu,Weijie Zhang
Background: Paclitaxel is a cornerstone of breast cancer treatment, but its efficacy is often limited by low response rates and drug resistance. To address this, we developed MEVs@CuET, a novel therapeutic approach combining cuproptosis-inducing copper(II) complex (CuET) with macrophage-derived extracellular vesicles (MEVs), aiming to enhance paclitaxel’s antitumor effects.Methods: The tumor-targeting capability of MEVs@CuET was evaluated through cellular uptake and in vivo distribution studies. In vitro synergy was assessed using the ZIP model, while transcriptome sequencing analyzed gene expression changes. In vivo antitumor activity and immune modulation were examined in breast cancer models, with tumor growth inhibition, apoptosis, and Th17 lymphocyte levels measured.Results: MEVs@CuET demonstrated efficient tumor targeting and synergistic antiproliferative effects with paclitaxel in vitro (synergy score: 29.37). Transcriptomic analysis revealed significant alterations in immune-related pathways, particularly upregulation of the IL-17 signaling pathway. In vivo, the combination therapy markedly inhibited tumor growth, increased apoptosis, and elevated Th17 cell levels, aligning with the transcriptomic findings.Conclusion: MEVs@CuET significantly enhances paclitaxel’s efficacy by inducing cuproptosis and modulating antitumor immunity, offering a promising strategy to overcome resistance in breast cancer treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2011
·
IF 7.883
Jing Li,Meirong Huo,Jing Wang,Jianping Zhou,Jumah M. Mohammad,Yinlong Zhang,Qinnv Zhu,Ayman Y. Waddad,Qiang Zhang
A targeted intracellular delivery system of paclitaxel (PTX) was successfully developed based on redox-sensitive hyaluronic acid-deoxycholic acid (HA-ss-DOCA) conjugates. The conjugates self-assembled into nano-size micelles in aqueous media and exhibited excellent drug-loading capacities (34.1%) and entrapment efficiency (93.2%) for PTX. HA-ss-DOCA micelles were sufficiently stable at simulated normal physiologic condition but fast disassembled in the presence of 20 m m reducing agent, glutathione . In vitro drug release studies showed that the PTX-loaded HA-ss-DOCA micelles accomplished rapid drug release under reducing condition. Intracellular release of fluorescent probe nile red indicated that HA-ss-DOCA micelles provide an effective approach for rapid transport of cargo into the cytoplasm. Enhanced cytotoxicity of PTX-loaded HA-ss-DOCA micelles further confirmed that the sensitive micelles are more potent for intracellular drug delivery as compared to the insensitive control. Based on flow cytometry and confocal microscopic analyses, observations revealed that HA-ss-DOCA micelles were taken up to human breast adenocarcinoma cells (MDA-MB-231) via HA-receptor mediated endocytosis . In vivo investigation of micelles in tumor-bearing mice confirmed that HA-ss-DOCA micelles possessed much higher tumor targeting capacity than the insensitive control. These results suggest that redox-sensitive HA-ss-DOCA micelles hold great potential as targeted intracellular delivery carriers of lipophilic anticancer drugs.
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
危险品化学品经营许可证（带存储）