JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Changmei Chen,Qinghua Yu,Lulu Wang,Rongchun Yi,Siying Huang,Xiangshu Cheng,Tao Deng
Chemotherapy combined with immunotherapy represents a promising combination therapy for tumor treatment. The low targeting of chemotherapeutic drugs and the potential immune-related adverse events (irAEs) of immune adjuvants hinder the realization of combination therapy. To solve these problems, we propose to further conjugate immunoadjuvant OVA using boric acid (BA) modified drug-carrying carbon dots, and develop a multifunctional nano drug delivery system for hierarchical targeting of focal sites (RCD@DOX/BA-O). From a mechanistic perspective, based on the pKa of BA, RCD@DOX/BA can couple OVA (1, 3-n-diol) under alkaline conditions and release OVA under tumor microenvironment, which could prevent the occurrence of irAEs. Furthermore, the exposed BA was able to combine with sialic acid (SA) (1, 2-n-diol) under the acidic tumor microenvironment, thereby enhancing its tumor-targeting capabilities. Specially, the immune effect (tumor-associated macrophages (TAMs) to M1) of OVA and the tumor targeted enhancement was verified by cell experiments. The treatment effect of RCD@DOX/BA-O was further proved on animal level. Overall, our finding suggests that the synthesized RCD@DOX/BA-O enabling synergistic chemotherapy and immunotherapy through hierarchical targeting to enhance anti-tumor efficacy and reduce irAEs. It is of great significance for targeted immunotherapy and improving the therapeutic effect of tumor.
研究领域:
纳米医学
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肿瘤学
·
免疫学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Pharmaceutical Innovation
·
2022
·
IF 2.538
Sun Yu
Purpose In this study, we fabricated a nanoplatform to target tumor sites via active and passive targeting effects, thus avoiding the toxic side effects of nanocarriers and improving the efficacy of chemotherapeutic drug delivery. Methods A sequential stimulus-responsive nanoparticle that targeted the tumor microenvironment and exhibited dual sensitivity to the reduction condition and matrix metalloproteinase-9 (MMP-9) enzyme was fabricated based on a self-assembled polypeptide-paclitaxel conjugate. Results The nanoparticles (48.9 ± 2.1 nm) transformed into rod-like nanostructures (297.1 ± 3.2 nm) in the presence of MMP-9. The rod-like nanostructures were taken up by tumor cells and then sensitive bonds were broken in response to highly expressed GSH in tumor cells to release drugs. This platform showed a tumor inhibition rate of 71.8% in S180-bearing mice and a more effective tumor inhibition rate than Taxol in 4T1-bearing mice. Conclusion This platform facilitates the design of enhanced safe and efficient chemotherapy drug delivery.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Nano Materials
·
2025
·
IF 5.5
Xueqing Li,Yulong Yan,Nannan Zhang,Xueling Liu,Xubo Zhao
Polydopamine (PDA) has demonstrated remarkable potential in the biomedical field due to its excellent biocompatibility. Exploring functional PDA can further enhance its application in drug delivery systems (DDS). In this study, we present a facile one-pot fabrication method for GSH- responsive PDA nanoparticles (NPs) through in situ formation of Mn3O4. Following PEGylation, the resultant functional DDS ((Mn3O4/PDA)-PEG) was used to encapsulate the chemotherapy drug doxorubicin (DOX), yielding DOX-loaded (Mn3O4/PDA)-PEG NPs. The findings indicate that the incorporation of Mn3O4 significantly enhances the responsiveness of PDA to tumor microenvironment stimuli, enabling GSH-triggered controlled drug release at specific sites. Moreover, Mn3O4 effectively prevents premature drug release under normal physiological conditions. Consequently, leveraging the GSH-responsiveness of the DDS facilitates the disassembly of PDA NPs, thereby markedly improving the bioavailability and therapeutic efficacy of chemotherapy drugs. This work encourages us to continue to prepare polydopamine materials with multiple functions through rational additive substances to improve the bioavailability of chemotherapy drugs.
研究领域:
生物医学工程
·
材料科学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2019
·Vol. 29
·期 15
·1808646
·
IF 15.621
Yinghao Zheng,Xinru You,Shuyu Guan,Jun Huang,Liying Wang,Jiayuan Zhang,Jun Wu
As colorectal cancer is the fourth leading cause of cancer-related death worldwide, colorectal cancer therapy requires new strategies for improved therapeutic effects. Recently, nanodrug carriers have emerged to weaken the systemic toxicity of chemotherapy drugs and strengthen the treatment effectiveness against colorectal cancer. In this report, ferulic acid, a plant derivative, is polycondensed into poly(ferulic acid) (PFA) for the first time to serve as an excellent drug carrier with anticancer performance. PFA self-assembles into nanoparticles by nanoprecipitation, and the screened PFA nanoparticles (NPs) have a diameter of ≈100 nm and possess a reasonable drug-loading capacity of ≈8.3% of paclitaxel (PTX). Evaluation of CT26 cells and a corresponding mouse model indicates remarkable inhibition of colon cancer with PTX-loaded PFA nanoparticles (PFA@PTX NPs) treatment both in vitro and in vivo. Meanwhile, evaluation of blank PFA NPs in a tumor mouse model also shows tumor inhibition, confirming that PFA itself has an anticancer effect in vivo. Overall, the novel nanoparticles based on poly(ferulic acid) can not only effectively deliver chemodrugs but also provide additional anticancer therapeutic effects, providing a promising platform for clinical colon cancer therapy.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2015
·Vol. 6
·期 8
·6368-6377
·
IF 3.84
Wenlong Wang,Liang Zhang,Mengtao Liu,Yuan Le,Shanshan Lv,Jiexin Wang,Jian-Feng Chen
Core cross-linked star-shaped polypeptides based on poly(L-glutamic acid)-poly(L-phenylalanine-co-L-cystine) copolymer have been successfully synthesized and thoroughly characterized. The star polypeptides can self-assemble to form 50 nm micelles in aqueous medium, which respond rapidly to both pH change within the physiologically relevant pH range and a reduction environment mimicking the intracellular space. Water-soluble doxorubicin hydrochloride and hydrophobic resveratrol are loaded into the star polypeptides micelles through electrostatic and hydrophobic interactions respectively. The drug loading content can be controlled by tuning the composition of the star polypeptides. The in vitro release studies indicate dual sensitivity enabled rapid drug release at pH 5.5 and 10 mM dithiothreitol (DTT), mimicking the intracellular environment. Furthermore, the star polypeptides are biocompatible and interact well with cells in vitro. Confocal fluorescence microscopy and flow cytometry assays show these star polypeptides can be quickly internalized and effectively deliver the drugs into HeLa cells to inhibit cell growth.
研究领域:
生物材料
·
药物递送系统
·
高分子化学
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2022
·Vol. 50
·期 4
·1-13
·
IF 5.314
Qinying Liu,Yi Yang,Miaomiao Cheng,Fangting Cheng,Shanshan Chen,Qiuhong Zheng,Yang Sun,Li Chen
Being a highly conserved catabolic process, autophagy is induced by various forms of cellular stress, and its modulation has considerable potential as a cancer therapeutic approach. In the present study, it was demonstrated that dicitrinone B (DB), a rare carbon‑bridged citrinin dimer, may exert anticancer effects by blocking autophagy at a late stage, without disrupting lysosomal function in MCF7 breast cancer and MDA‑MB‑231 triple‑negative breast cancer cells. Furthermore, it was discovered that DB significantly enhanced intracellular reactive oxygen species (ROS) production and that the removal of ROS was followed by the attenuation of autophagy inhibition. In addition, DB exerted notable inhibitory effects on the proliferation and promoting effects on the apoptosis of MCF7 and MDA‑MB‑231 cells. In combination with conventional chemotherapeutic drugs, DB exhibited a further enhanced synergistic effect than when used as a single agent. Overall, the data of the present study demonstrate that DB may prove to be a promising autophagy inhibitor with anticancer activity against breast cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Chaochen Shi,Tao Chen,Yingying Li,Wenshuai Li,Yuan Shen,Kehan Cai,Ming Wang,Yazhou Chen
Cell-based delivery holds great promise for advancing cell therapy, but it often faces challenges such as low cell survival rates and immunological rejection during cell injection and circulation. In this study, we develop an alternative approach aimed at engineering cell membranes to produce encapsulated individual mammalian (EIM) cells. The encapsulation shell was formed by catalyzing the reaction of H 2 O 2 with hyaluronic acid-dopamine (HA-DA) on the cell surface using horseradish peroxidase (HRP) enzymes. This protective shell not only protects live mammalian cells from physical stress but also from biological assaults. The individual cell encapsulation system enables the loading of cells with chemotherapy drugs, enhancing their targeting ability towards tumor sites and resulting in over 5.1-fold cell enrichment at metastatic tumors, thereby improving tumor-killing efficacy and reducing metastasis. Overall, the individual cell encapsulation system demonstrates potential for targeted drug delivery to the lungs in the treatment of lung cancer by reducing side effects and enhancing treatment outcomes.
研究领域:
生物医学工程
·
肿瘤学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2019
·Vol. 43
·期 6
·2752-2757
·
IF 3.069
Xinyu Cui,Wenlong Cheng,Mingdong Dong,Xiaojun Han
Controlled drug release is a promising technique that is used in the treatment of cancer. Herein, drug nanocarriers were developed based on Fe3O4@mSiO2 (mesoporous silica-coated Fe3O4) nanoparticles (NPs) gated by a lipid bilayer. The nanocarriers exhibited near-infrared (NIR) light-stimulated drug release in a remote and stepwise pattern. Mesoporous silica surrounds Fe3O4 NPs and ensures high drug capacity and easy modification of the lipid bilayer. Heat generated from the Fe3O4 NPs upon NIR irradiations increases the permeability of the lipid bilayer, which in turn causes drug release. Based on in vitro experiment results, DOX-loaded nanocarriers exhibited the highest cell death percentage of 75.7% with NIR laser irradiation for 5 min at the doxorubicin (DOX) dose of 10 μg mL−1. Because of the flexible and precise control of NIR laser, the nanocarriers have great potential in cancer treatment.
研究领域:
生物材料学
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Lina Liang,Jun Fu,Liyan Qiu
pH-responsive polymersomes have emerged as promising nanocarriers for antitumor drugs to realize their fast release and action in a weakly acidic microenvironment of tumor cells. Herein, however, we designed a remarkably pH-responsive polymersome self-assembled from amphiphilic benzimidazole-based polyphosphazenes via the incorporation of cholesteryl hemisuccinate (CholHS), a type of cholesteric molecule, into the polymersome bilayers to inhibit the drug release during blood circulation. Actually, unwanted premature drug leakage before arriving at the acidic tumor site has become a serious problem for polymersomes encapsulating water-soluble drugs, especially when the drug loading is at a high level, thus limiting the therapeutic efficacy. In this study, polymersomes displayed high loading capability of doxorubicin hydrochloride as 12.83%. More importantly, CholHS incorporation decreased the membrane permeability of the polymersome and effectively retarded the cargo release under physiological conditions but induced the fast drug-release rate at pH 5.5, demonstrating a more remarkably acid-responsive release behavior when compared to that of the CholHS-free polymersomes. Further in vivo investigations including pharmacokinetic and antitumor activity studies verified the extended circulation time and enhanced antitumor efficacy of the drug-loaded CholHS-incorporated polymersomes.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2017
·
IF 5.246
Jia Tian,Lei Xu,Yudong Xue,Xiaoze Jiang,Weian Zhang
Drug resistance is a primary obstacle that seriously reduces the therapy efficiency of most chemotherapeutic agents. To address this issue, the photochemical internalization (PCI) was employed to help the anticancer drug escape from lysosome and improve their translocation to the nucleus. A pH-sensitive porphyrin-based amphiphilic block copolymer (PEG113-b-PCL54-a-porphyrin) was synthesized, which was acted not only as a carrier for the delivery of DOX but also as a photosensitizer for PCI. PEG113-b-PCL54-a-porphyrin as a drug carrier exhibited a higher drug loading capacity, entrapment efficiency, and DOX release content. The PCI effect of PEG113-b-PCL54-a-porphyrin was studied by confocal laser scanning microscopy, and the results showed that most of DOX could be translocated into the nucleus for DOX-loaded PEG113-b-PCL54-a-porphyrin micelles. Moreover, the IC50 of pH-sensitive DOX-loaded PEG113-b-PCL54-a-porphyrin micelles was much lower than that of its counterpart without pH-responsiveness, DOX-loaded PEG113-b-PCL54-porphyrin micelles. Therefore, this drug delivery system based on pH-sensitive porphyrin-containing block copolymer would act as a potential vehicle for overcoming drug resistance in chemotherapy.
研究领域:
药学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Ying Xu,Peng Chen,Lei Tang,Xiaojun Zhang,Feng Shi,Xuyang Ning,Jingli Bi,Yang Qu,Hongfei Liu
Most chemotherapy agents have serious side effects due to lack of tumor targeting, which affects their clinical application. In addition, as an essential characteristic of malignant tumor, hypoxia is attracting exclusive research focus regarding its non-invasive real-time tracing in novel targeting delivery system. Herein, we designed a mixed micelle with tumor targeting and hypoxia responsiveness for tumor therapy and imaging. In particular, the dual-modified mix micelles were self-assembled by folic acid (FA) and 2-(2-nitroimidazole) ethylamine (NI) conjugated polymers , in which paclitaxel (PTX) and quantum dots (QDs) were co-loaded into the hydrophobic core. The drug loaded micelles showed satisfactory drug encapsulation, good storage stability, and sustained release properties. In vitro cell experiments showed that the mixed micelles exhibited enhanced cytotoxic effect and improved the cellular uptake, especially under hypoxic conditions, which was due to the FA mediated active targeting effect and NI induced hypoxic responsive release. In vivo experiments further proved that the mixed micelles possessed outstanding tumor targeting and hypoxia responsive properties. Furthermore, the drug loaded micelles showed excellent anti-tumor effect and can realize real-time in vivo imaging. This work demonstrates that the dual-modified mixed micelles co-loading with PTX and QDs might provide a novel approach for tumor therapy and imaging.
研究领域:
药剂学
·
肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Mi Zhou,Jiahuan Hong,Xiaofeng Qiu,Zixian Xiong,Xiaoyong Liu,Zhuan Qin,Zhesi Luo,Qi Chen,Mianjie Lin,Ling Min,Xiaorong Yang,Xinmin Guo,Bin Xu,Jianwen Mao
Multidrug resistance (MDR) in tumor cells presents a significant challenge in cancer therapy. This study investigates the role of serum-derived extracellular vesicles (EVs) in mediating MDR during chemotherapeutic exposure. The findings indicate that short- or long-term co-incubation of doxorubicin (Dox)-pretreated serum derived EVs (EVs(S-PT)) caused drug-sensitive MCF-7 breast cancer cells to develop a MDR phenotype. In addition, serum EVs contain a high concentration of unglycosylated P-glycoprotein (P-gp). Chemotherapy treatment of tumor patients or exposure to chemotherapeutic drugs in vitro activates serum glycosyltransferases, inducing glycosylation of EVs P-gp and giving it drug-pumping activity. Furthermore, damage caused by Dox to the vascular endothelial barrier facilitates the crossing of serum EVs into the tumor microenvironment. These EVs are then taken up by tumor cells, providing them with access to a significant quantity of glycosylated P-gp proteins that possess transporter activity and the ability to evade degradation by the ubiquitin proteasome system. The results indicate that EVs(S-PT) transfers glycosylated P-gp across the damaged vascular endothelial barrier into MCF-7 cells and that these glycosylated P-gp remain intracellular for a long period of time, inducing MDR in the cells. Our study highlights a novel mechanism of acquired MDR and provides a potential avenue for therapeutic interventions targeting the serum EVs pathway in cancer therapy.
研究领域:
肿瘤学
·
细胞生物学
·
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）