ANALYTICAL LETTERS
·
2021
·
IF 2.329
Penghui Jin,Daoqing Ma,Yabiao Gao,Libin Wang,Zhihong Gao,Yating Zhang,Mingxin Liu,Jingying Xu,Jidong Wang
A highly sensitive and dual-directional fluorescent sensing system was developed to detect both cisplatin prodrug cross-linked hyaluronic acid (CPHA) hydrogel (quencher) and DNA (receptor) based on mercaptopropionic acid (MPA) capped CdTe quantum dots (QDs). Different from the previous work for this platinum compound, a multifunctional delivery system, CPHA hydrogel, which was used to address the challenges in drug resistance and severe side effects, was prepared and accurately detected based on the synthesis of the cisplatin prodrug and fluorescence quenching of CdTe QDs resulting from photo-induced electron transfer. When DNA was conjugated with Pt ions in a system composed of CdTe QDs and CPHA hydrogel, the fluorescence of the system was recovered for the determination of DNA. This reversible “turn off–on” strategy presented a high sensitivity and low detection for CPHA hydrogel from 10 to 50 nM with a detection limit of 1.50 nM and DNA from 0 to 75 nM with a detection limit of 0.60 nM. This approach provides a novel direction for further study of the Pt based drug-load with reduced side effects and improved therapy efficacy, effective screening of anticancer drugs, and accurate determination of DNA at low concentrations.
研究领域:
生物医学工程
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药物化学
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分析化学
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产品关联
DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2025
·
IF 5.4
Lei Yang,Lang Ran,Yu Li,Yi’ao Tan,Dian Xia,Tao Huang,Jing Wang,Tingting Jiang,Tao Tao,Jianmin Xiao,Shuhan Liu
Cisplatin as a first-line drug showed some significant limitations in clinical use owing to seriously systemic toxicity, and acquired drug-resistance. Herein, we utilized PC-3 cell membrane camouflaged Mn-doped metal-organic framework to deliver low toxic tetravalent cisplatin prodrug (mMOF-Pt) for synergistic chemodynamic therapy (CDT) and chemotherapy of prostate tumor. Owing to homologous targeting action, the mMOF-Pt actively recognized prostate tumor. Upon special tumor microenvironment, the mMOF-Pt released ciplatin prodrug. Next, the tetravalent cisplatin prodrug could be reduced into high toxic cisplatin by over-expressed GSH, effective killing tumor cells. Meanwhile, the MOF catalyzed endogenous H 2 O 2 into highly toxic ·OH via Fenton-like reaction, which induced intracellular ROS production and significantly elevated oxidative stress level. Strong oxidative stress dramatically enhanced the sensitivity of tumor cells to chemotherapeutic drug, further amplifying the toxicity of cisplatin to tumor cells. In vivo experiment results demonstrated that the mMOF-Pt effectively accumulated in tumor site and significantly inhibited the growth of prostate tumor within low systemic toxicity. Moreover, the mMOF-Pt could be completely excreted out from body, which avoided potential risk for body. Overall, we considered that this work provided a great strategy for improving therapy of prostate cancer.
研究领域:
肿瘤学
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生物医学工程
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药理学
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纳米技术
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产品关联
DOI
高影响因子
Polymer Chemistry
·
2014
·Vol. 5
·期 11
·3707-3718
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IF 5.368
Yu Han,Junjie Li,Minghui Zan,Shizhong Luo,Zhishen Ge,Shiyong Liu
Responsive cross-linked block copolymer micelles which have emerged as promising drug delivery systems showed high stability and on-demand drug release. The combination therapy of cancer can be achieved via co-delivery of varying therapeutic molecules in one system. Here, we developed a redox-responsive core cross-linked (CCL) micelle conjugated with cypate and cisplatin prodrugs within the cores for synergistic photothermal and chemotherapy. The block copolymer, poly[(2-(2-methoxyethoxy)ethyl methacrylate)-co-(N-methacryloxy succinimide)]-block-poly(N-(2-hydroxypropyl) methacrylamide) (P(MEO2MA-co-MASI)-b-PHPMA), was synthesized via reversible addition–fragment chain transfer (RAFT) polymerization. After partial amidation reaction of succinimide with 3-azidopropylamine, the alkynyl-functionalized cypate and Pt(IV) complex were conjugated via click reaction. The CCL micelles were fabricated by core cross-linking at 37 °C in aqueous solution using cystamine as the cross-linker. P(Pt-Cy-MEO2MA)-b-PHPMA CCL micelles showed redox-responsive cross-linker cleavage and cisplatin drug release in the presence of reductants. The conjugated cypate moieties in the cores of CCL micelles resulted in photothermal temperature increase and reactive oxygen species (ROS) generation under 805 nm near infrared (NIR) laser irradiation. The cytotoxicity of CCL micelles was investigated with and without NIR irradiation. A significant synergistic effect of photothermal therapy and chemotherapy was demonstrated against cisplatin-resistant human lung cancer cells A549R under NIR irradiation.
研究领域:
癌症治疗
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药物递送系统
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高分子化学
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纳米医学
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2017
·
IF 7.786
Yuanfeng He,Yanjuan Huang,Ziyuan Huang,Yali Jiang,Xiaoqi Sun,Yifeng Shen,Weijing Chu,Chunshun Zhao
Bone is the most common organ affected by metastatic breast cancer . Targeting cancers within the bone remains a great challenge due to the inefficient delivery of therapeutic to bone. In this study, a polyethylene glycol (PEG) coated nanoparticles (NPs) made of a Zn 2 + coordination polymer was linked with a bone seeking moiety, alendronate (ALN), to deliver cisplatin prodrug (DSP) to the bone. The particle sizes of this novel system, [email protected] NPs, were regulated by adjusting the volume ratio of water phase to oil phase in microemulsion . It was small enough (about 55 nm) to extravasate through the clefts (80 nm) of the bone's sinusoidal capillaries and localize into metastatic bones. [email protected] NPs showed much higher affinity for hydroxyapatite in vitro and bone in vivo than non-targeted [email protected] NPs and cisplatin. In addition, the in vivo biodistribution studies demonstrated that about 4-fold of platinum was delivered to the bone metastatic lesions than that in healthy bones by [email protected] NPs intravenously. Finally, [email protected] NPs not only inhibited the tumor growth efficiently but also reduced the osteocalastic bone destruction. Besides, [email protected] NPs showed significantly reduced toxicity of cisplatin. These results indicate that the [email protected] NPs have a great potential in enhancing chemotherapeutic efficacy for the treatment of bone metastatic breast cancer.
研究领域:
肿瘤学
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药物递送系统
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骨生物学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2016
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IF 7.145
Wei Zhang,Jianliang Shen,Hua Su,Ge Mu,Jing-Hua Sun,Cai-Ping Tan,Xing-Jie Liang,Liang-Nian Ji,Zong-Wan Mao
Combination therapy shows great promise in circumventing cisplatin resistance. We report herein the development of a novel nanoscale drug delivery system (nDDS) based nanotherapeutic that combines chemotherapy and photodynamic therapy (PDT) into one single platform to achieve synergistic anticancer capacity to conquer cisplatin resistance. Mesoporous silica nanoparticle (MSNs) was used as the drug delivery vector to conjugate cisplatin prodrug and to load photosensitizer chlorin e6 (Ce6) to afford the dual drug loaded delivery system MSNs/Ce6/Pt. The hybrid nanoparticles have an average diameter of about 100 nm and slightly positive surface charge of about 18.2 mV. The MSNs/Ce6/Pt nanoparticles can be efficiently internalized by cells through endocytosis, thereby achieving much higher cellular Pt uptake than cisplatin in cisplatin-resistant A549R lung cancer cells. After 660 nm light irradiation (10 mW/cm2), the cellular reactive oxygen species (ROS) level in MSNs/Ce6/Pt treated cells was elevated dramatically. As a result of these properties, MSNs/Ce6/Pt exhibited very potent anticancer activity against A549R cells, giving a half-maximal inhibitory concentration (IC50) value for the combination therapy of 0.53 μM, much lower than that of cisplatin (25.1 μM). This study suggests the great potential of nDDS-based nanotherapeutic for combined chemo-photodynamic therapy to circumvent cisplatin resistance.
研究领域:
纳米医学
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肿瘤学
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制药学
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材料科学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xinmin Zheng,Xiang Li,Guolin Shi,Yidan Zhou,Jinxiao Yan,Hao Zhang,Xiru Liu,Jiangong Zhang,Yu Liu,Liangliang Dai,Hui Yang
The low targeting of immunity regulators & chemotherapy drugs and immune tolerance in the tumor microenvironment significantly hindered the chemo-immunotherapy effect. In this work, an MMP-2/GSH-responsive nanobomb loading Resiquimod (R848) and prodrug Cisplatin (Pt) with hierarchical drug delivery and tumor associated macrophages (TAMs) polarization traits was designed for improved chemo-immunotherapy. The Pt-carrying dendrimers penetrate the depth of tumor tissues under MMP-2 and activate the cytotoxicity of Pt prodrug in response to GSH, causing effective tumor damage and enhancing immunogenicity. Meanwhile, R848 is effectively uptake by TAMs, which were re-educated and then greatly relieved immune resistance. In vitro and in vivo results collectively revealed that the nanosystem could not only overcome the barrier of tumor penetration and the heterogeneity action sites of drugs but also re-educate TAMs and suppress immune evasion via activating extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signal pathway regulated by heparin binding EGF like growth factor ( Hbegf ) gene. The gene silencing or knockout in vitro and in vivo demonstrated that Hbegf could regulate the re-education of TAMs and the progression of tumors.
研究领域:
肿瘤学
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免疫学
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药剂学
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产品关联
DOI
高影响因子
ACS Nano
·
2025
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IF 16
Xuanbo Zhang,Shipeng Ning,Feng Fang,Cao Zhou,Zifan Yang,Liping Cao,Kaiyuan Wang,Zunyong Feng,Bingyu Li,Dixian Luo,Xiao Xu,Zhigang Liu,Xiaoyuan Chen,Zhiqiang Yu
Cisplatin’s clinical utility is limited by its toxicity, drug resistance, and promotion of immune suppression due to phosphatidylserine (PS) exposure during tumor cell apoptosis. This study introduces a novel approach that integrates cisplatin-derived lipid prodrugs into lipid nanoparticles (PtLNPs) to overcome these challenges. By converting cisplatin to lipid derivatives, we facilitate its incorporation into LNPs, enhancing both the delivery and protection of functional siRNA/mRNA molecules. The synthesized lipid–Pt prodrugs significantly improved the in vitro delivery efficiency and stability of these nucleic acids. Additionally, a codelivery system combining Xkr8 siRNA and annexin A5 (ANX5) mRNA within PtLNPs effectively mitigated cisplatin-induced PS exposure by inhibiting Xkr8 upregulation and promoting ANX5 expression to bind PS. In vivo studies demonstrated that the PtLNP system substantially enhanced the efficacy of combined chemotherapy and immunotherapy, offering a promising strategy to refine cisplatin-based cancer therapy by integrating nucleic acid delivery technologies.
研究领域:
肿瘤学
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药剂学
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分子生物学
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免疫学
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转化医学
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药物代谢
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2017
·
IF 8.402
Rui Zhang,Xuejiao Song,Chao Liang,Xuan Yi,Guosheng Song,Yu Chao,Yu Yang,Kai Yang,Liangzhu Feng,Zhuang Liu
Aiming at improved therapeutic efficacies, the combination of chemotherapy and radiotherapy (chemo-radiotherapy) has been widely studied and applied in clinic. However, the hostile characteristics of tumor microenvironment such as hypoxia often limit the efficacies in both types of cancer therapies. Herein, catalase (CAT), an antioxidant enzyme , is encapsulated inside liposomes constituted by cisplatin (IV)-prodrug-conjugated phospholipid , forming [email protected] (IV)-liposome for enhanced chemo-radiotherapy of cancer. After being loaded inside liposomes, CAT within [email protected] (IV)-liposome shows retained and well-protected enzyme activity , and is able to trigger decomposition of H 2 O 2 produced by tumor cells, so as to produce additional oxygen for hypoxia relief. As the result, treatment of [email protected] (IV)-liposome induces the highest level of DNA damage in cancer cells after X-ray radiation compared to the control groups. In vivo tumor treatment further demonstrates a remarkably improved therapeutic outcome in chemo-radiotherapy with such [email protected] (IV)-liposome nanoparticles . Hence, an exquisite type of liposome-based nanoparticles is developed in this work by integrating cisplatin-based chemotherapy and catalase-induced tumor hypoxia relief together for combined chemo-radiotherapy with great synergistic efficacy, promising for clinical translation in cancer treatment.
研究领域:
肿瘤学
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药物科学
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纳米技术
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放射肿瘤学
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DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
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2025
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IF 14.6
Tianyue Xu,Dan Zheng,Meixu Chen,Linlin Song,Zhihui Liu,Yan Cheng,Yujie Zhao,Liwen Huang,Yixuan Li,Zhankun Yang,Cong Li,Biao Dong,Jing Jing,Hubing Shi
Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo . Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.
研究领域:
肿瘤学
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药剂学
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放射生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science China-Life Sciences
·
2024
·
IF 8
Wang Shuxiang,Cao Hongmei,Zhao Cui-Cui,Wang Qian,Wang Dianyu,Liu Jinjian,Yang Lijun,Liu Jianfeng
Tumor cells establish a robust self-defense system characterized by hypoxia, antioxidant overexpression, DNA damage repair, and so forth to resist radiotherapy. Targeting one of these features is insufficient to overcome radioresistance due to the feedback mechanisms initiated by tumor cells under radiotherapy. Therefore, we herein developed an engineering biomimetic nanosystem (M@HHPt) masked with tumor cell membranes and loaded with a hybridized protein-based nanoparticle carrying oxygens (O 2 ) and cisplatin prodrugs (Pt(IV)) to target multiple tumor radioresistance hallmarks for enhanced radiotherapy. After administration, M@HHPt actively targeted and smoothly accumulated in tumor cells by virtue of its innate homing abilities to realize efficient co-delivery of O 2 and Pt(IV). O 2 introduction induced hypoxia alleviation cooperated with Pt(IV) reduction caused glutathione consumption greatly amplified radiotherapy-ignited cellular oxidative stress. Moreover, the released cisplatin effectively hindered DNA damage repair by crosslinking with radiotherapy-produced DNA fragments. Consequently, M@HHPt-sensitized radiotherapy significantly suppressed the proliferation of lung cancer H1975 cells with an extremely high sensitizer enhancement ratio of 1.91 and the progression of H1975 tumor models with an excellent tumor inhibition rate of 94.7%. Overall, this work provided a feasible strategy for tumor radiosensitization by overcoming multiple radioresistance mechanisms.
研究领域:
纳米技术
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癌症研究
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放射肿瘤学
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Haibin Lu,Weifang Tong,Meixu Jiang,Huimin Liu,Chen Meng,Kai Wang,Xupeng Mu
How to address the resistance of cisplatin (CDDP) has always been a clinical challenge. The resistance mechanism of platinum-based drugs is very complex, including nuclear DNA damage repair, apoptosis escape, and tumor metabolism reprogramming. Tumor cells can switch between mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis and develop resistance to chemotherapy drugs through metabolic variability. In addition, due to the lack of histone protection and a relatively weak damage repair ability, mitochondrial DNA (mtDNA) is more susceptible to damage, which in turn affects mitochondrial OXPHOS and can become a potential target for platinum-based drugs. Therefore, mitochondria, as targets of anticancer drugs, have become a hot topic in tumor resistance research. This study constructed a self-assembled nanotargeted drug delivery system LND-SS-Pt-TPP/HA-CD. β-Cyclodextrin-grafted hydronic acid (HA-CD)-encapsulated prodrug nanoparticles can target CD44 on the tumor surface and further deliver the prodrug to intracellular mitochondria through a triphenylphosphine group (TPP+). Disulfide bonds can be selectively degraded by glutathione (GSH) in mitochondria, releasing lonidamine (LND) and the cisplatin prodrug (Pt(IV)). Under the action of GSH and ascorbic acid, Pt(IV) is further reduced to cisplatin (Pt(II)). Cisplatin can cause mtDNA damage, induce mitochondrial dysfunction and mitophagy, and then affect mitochondrial OXPHOS. Meanwhile, LND can reduce the hexokinase II (HK II) level, induce destruction of mitochondria, and block energy supply by glycolysis inhibition. Ultimately, this self-assembled nano targeted delivery system can synergistically kill cisplatin-resistant lung cancer cells, which supplies an overcome cisplatin resistance choice via the disrupt mitochondria therapy.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2025
·
IF 14.6
Yupei Zhang,Shugang Qin,Tingting Song,Zhiying Huang,Zekai Lv,Yang Zhao,Xiangyu Jiao,Min Sun,Yinghan Zhang,Guang Xie,Yuting Chen,Xuli Ruan,Ruyue Liu,Haixing Shi,Chunli Yang,Siyu Zhao,Zhongshan He,Hai Huang,Xiangrong Song
Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood–brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a “Hitchhiking Effect” mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.
研究领域:
肿瘤学
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纳米医学
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药物递送
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神经病学
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生物化学
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计算生物学
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分子靶向治疗
✓ 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）