ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Yadong Liu,Yifan Xue,Junjie Tang,Peng Zhang,Changjiang Liu,Dalin Wu,Jie Liu
Porphyrin-based photosensitizers are extensively utilized in the realm of photodynamic therapy, capitalizing on their advantageous optical, chemical, and electronic properties. Nonetheless, their application is often constrained by their pronounced hydrophobicity. Structures with a high load capacity and excellent biocompatibility are preferred options to circumvent this obstacle. Herein, we constructed a novel porphyrin–camptothecin (CPT) polymer, which is composed of amphiphilic oxazoline segments, and the drug monomers containing disulfide bonds are modified on the hydrophobic chain of polyoxazoline. The polyoxazoline–porphyrin–CPT (OPC) polymer can self-assemble into nanoparticles in the aqueous phase, possesses excellent stability, and generates abundant singlet oxygen (1O2) under laser irradiation. Additionally, the OPC nanoparticles exhibit satisfactory biocompatibility and high light toxicity against 4T1 cells. In the microenvironment of the tumor, drugs were released from the OPC nanoparticles owing to the high concentration of GSH, causing direct damage to the tumor cell, achieving the combination of photo-chemotherapy. The findings of this research indicate that polyoxazoline porphyrin demonstrates adaptability as a nanoplatform for cancer treatment.
研究领域:
药学
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纳米技术
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生物医学工程
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2018
·Vol. 14
·期 10
·1731-1743
·
IF 5.068
Liu Fulei,Han Lingfei,Huang Xiaoxian,Sang Mangmang,Liu Bowen,Li Cong,Ma Congyu,Liu Wenyuan,Feng Feng,Qu Wei
Hyaluronic acid (HA) is widely used in many tumor targeting drug delivery systems (TDDS) due to its biocompatibility and modifiability. Moreover, HA receptors are over-expressed on many tumor cells. However, the clearance of the HA-related TDDS by the reticuloendothelial system (RES)
need urgent consideration on account of the high affinity between HA and related receptors in RES. A pre-block strategy before TDDS administration had been designed to overcome RES clearance. In order to avoid the rapid RES clearance and further improve tumor targeting efficiency for HA-related
TDDS, we designed a novel strategy of selectively pre-blocking HA receptors in RES by injecting HA-coated blank liposome (pre-block formulation) prior to dosing of HA-related TDDS. The molecule weight and surface density of HA in pre-block formulation as well as TDDS, the time interval between
dosing, and the concentration of pre-block formulation, were optimized by a series of in vitro cellular uptake studies in macrophages and 4T1 tumor cell lines, which was further confirmed by in vivo studies. The result shows that that the optimized pre-block formulation can saturate
the RES, by which the RES clearance is weakened and the tumor targeting efficiency for HA-related TDDS is finally improved.
研究领域:
药学
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癌症研究
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
·
2023
·
IF 6
Xue Wang,Mengli Zhao,Jianmin Feng,Dejun Li
In this paper, polycrystalline molybdenum disulfide (MoS 2 ) nanoflowers were prepared by mixing ammonium molybdate tetrahydrate [(NH 4 ) 6 Mo 7 O 24 ·4H 2 O] and potassium thiocyanate (KSCN) at 300 °C for 2 h via molten salt sintering method. Under scanning electron microscope (SEM) and high-resolution transmission electron microscope (HRTEM), MoS 2 showed popcorn-like shape, which surface distribution defects were easy to be further modified. MoS 2 as a nano-enzyme was used to inhibit the proliferation of mouse breast cancer cells (4 T1), which had 69.8 % inhibitory effect on 4 T1 cell proliferation. Electron spin resonance (ESR) analysis showed that MoS 2 could produce a large number of stable hydroxyl radicals (–OH). The disulfide bond in MoS 2 was highly sensitive to reactive oxygen species (ROS). High ROS level leads to the death of cancer cells under oxidative stress and inhibits the proliferation of 4 T1. This work demonstrates that MoS 2 is a potential anticancer drug or carrier for cancer treatment.
研究领域:
材料科学
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纳米技术
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癌症研究
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生物医学工程
✓ 已验证
DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2022
·Vol. 46
·期 21
·10289-10298
·
IF 3.925
Jiao Yang Lu,Xiaolong Zhou,Jialiang Yang,Yi Zhou,Binsheng He,Wei Tao Huang,Yajing Wang,Zhen Guo
Invasion and migration are major characteristics of malignant cancers. Inhibiting the migration of cancer cells, rather than simply removing the primary tumor, is essential for improving the survival rates. Two-dimensional (2D) materials have important application prospects in the field of biomedicine (especially in cancer therapy) due to their unique physicochemical properties. However, the basic biological effects of 2D material cobalt-based layered double hydroxides, especially its cytotoxicity and migration effects on a variety of cells, have not yet been revealed. Herein, the effect of 5 nm thick β-Co(OH)2 nanosheets (NSs) on cell viability and migration of normal cells and various cancer cells and their possible mechanisms were investigated. The cell viability assay and migration ability analysis found that β-Co(OH)2 NSs had a concentration-dependent and selective biological effects on normal cells HUVEC and cancer cells (4T1, SMMC-7721, and B16 cells). Compared with normal cells HUVEC, β-Co(OH)2 NSs showed remarkably stronger and differentiated cytotoxicity to cancer cells (4T1, SMMC-7721, and B16 cells), and it was found by wound healing and transwell assays that β-Co(OH)2 NSs also can inhibit cancer cell migration more sensitively which may be attributed to the down-regulation of the key epithelial-mesenchymal transition protein Snail2. This study on revealing the basic biological effects of cobalt-based nanosheets will not only promote the understanding of the interaction between nanosheets and cells, but will also help in developing cancer treatment platforms based on cobalt-based nanosheets to promote their applications in the inhibition of tumor migration and metastasis.
研究领域:
生物医学工程
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纳米技术
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癌症研究
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细胞生物学
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 15
·2499-2511
·
IF 5.047
Qianglan Lu,Sun Qi,Peishan Li,Lifang Yang,Shan Yang,Yidan Wang,Yu Cheng,Yilin Song,Siyu Wang,Fengping Tan,Nan Li
Photothermal therapy (PTT) has shown promising potential and bright prospects in damaging primary tumors; however, it is limited to metastatic and recrudescent tumors as PTT requires straightforward light irradiation. Moreover, metastatic and recrudescent tumor immunosuppression due to host T-cell antitumor activity is dramatically impeded because of programmed cell death 1 ligand (PD-L1) and programmed cell death receptor 1 (PD-1) pathways and immune checkpoint blockade (ICB) therapy. In this work, we demonstrate that PTT combined with ICB could not only eliminate primary tumors, but also prevent tumor metastasis to the lungs/liver. In particular, we have designed immunoadjuvant nanomedicine carriers on the basis of polydopamine (PDA) simultaneously loaded with resiquimod (R848)—a kind of toll-like receptor 7 (TLR7) agonist—and carbon dots (CDs)—a fluorescent agent. This nanomedicine is defined as PDA-PEG-R848-CD nanoparticle (NP). The multitasking PDA-PEG-R848-CD NPs can destroy 4T1 breast tumors by PTT under near-infrared laser irradiation in addition to generating tumor-associated antigens. Moreover, the PTT effect triggered the release of R848, thereby inducing a strong antitumor immune response. Meanwhile, this synergistic therapy also shows the abscopal effects by completely inhibiting the growth of untreated distant tumors by effectively triggering the tumors infiltrated by CD3/CD8. Such findings suggest that PDA-PEG-R848-CD NPs could significantly potentiate the systemic therapeutic efficiency of PD-L1 checkpoint blockade therapy by activating both innate and adaptive immune systems in the body.
研究领域:
癌症研究
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纳米技术
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免疫疗法
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
POWDER TECHNOLOGY
·
2018
·
IF 3.23
Chao Qin,Xin Yang,Yubing Wu,Yaqi Lv,Li Zhang,Xiaofei Xin,Lei Yang,Wei He,Xiaopeng Han,Lifang Yin,Chunyong Wu
ABSTRACT A matrix metalloproteinases (MMPs) triggered multifunctional micellar system loading traditional chemotherapeutic agent paclitaxel (PTX) and marimastat (MATT), an inhibition of matrix metalloproteinases, was established to prevent tumor growth and metastasis. The micelles were self-assembled by the conjugate synthesized with an MMPs sensitive peptide as the bridge between PTX and poly(ethylene glycol) (PEG). 4T1 cell line derived from a murine breast tumor was selected as the cell model due to its high metastasis. The cytotoxicity assay and cell apoptosis analysis revealed that the sensitive micelles increased the toxicity and cell apoptosis compared with the insensitive micelles. In addition, this system also exhibited high penetration ability in tumor spheroids and significant invasion inhibition with the method of Transwell invasion assay. In the BALB/c mice bearing 4T1 tumors, this system inhibited the growth of the metastatic tumor and prevented the incidence of lung metastasis with low systemic toxicity. And the expression of MMP-2 and MMP-9, which are important in the process of tumor metastasis, was down-regulated. Generally, the data obtained from the in vitro and in vivo studies confirmed that the codelivery of PTX and MATT by the MMPs sensitive micelles achieved not only significant antitumor effect but also obvious inhibition effect of tumor metastasis, which are the leading cause of cancer deaths. This functional particle system may provide a promising strategy for metastatic breast cancer therapy.
研究领域:
肿瘤学
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药学
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生物医学工程
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产品关联
DOI
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 5
·632
·
IF 4.9
Weixiang Fang,Kailing Yu,Songhan Zhang,Lai Jiang,Hongyue Zheng,Qiaoling Huang,Fanzhu Li
A nanoparticle’s shape is a critical determinant of its biological interactions and therapeutic effectiveness. This study investigates the influence of shape on the performance of mesoporous silica nanoparticles (MSNs) in anticancer therapy. MSNs with spherical, rod-like, and hexagonal-plate-like shapes were synthesized, with particle sizes of around 240 nm, and their other surface properties were characterized. The drug loading capacities of the three shapes were controlled to be 47.46%, 49.41%, and 46.65%, respectively. The effects of shape on the release behaviors, cellular uptake mechanisms, and pharmacological behaviors of MSNs were systematically investigated. Through a series of in vitro studies using 4T1 cells and in vivo evaluations in 4T1 tumor-bearing mice, the release kinetics, cellular behaviors, pharmacological effects, circulation profiles, and therapeutic efficacy of MSNs were comprehensively assessed. Notably, hexagonal-plate-shaped MSNs loaded with PTX exhibited a prolonged circulation time (t1/2= 13.59 ± 0.96 h), which was approximately 1.3 times that of spherical MSNs (t1/2= 10.16 ± 0.38 h) and 1.5 times that of rod-shaped MSNs (t1/2= 8.76 ± 1.37 h). This research underscores the significance of nanoparticles’ shapes in dictating their biological interactions and therapeutic outcomes, providing valuable insights for the rational design of targeted drug delivery systems in cancer therapy.
研究领域:
纳米技术
·
癌症治疗
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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
Biomaterials Science
·
2019
·Vol. 8
·期 1
·325-332
·
IF 5.251
Haiyang Yu,Na Shen,Yanli Bao,Li Chen,Zhaohui Tang
Although the polymeric vascular disrupting agent (poly(L-glutamic acid)-graft-methoxy poly(ethylene glycol)/combretastatin A4) nanoparticles (CA4-NPs) has great potential to inhibit cancer growth, it is still a challenge to avert tumor recurrence and metastasis after treatment. It is mainly tightly associated with hypoxia induced by CA4-NPs, which can activate many downstream genes regulating tumor growth and metastasis. Herein, to relieve a tumor hypoxia microenvironment, the mTOR inhibitor temsirolimus was employed to modulate the tumor microenvironment when treated with CA4-NPs. In vitro MTT experiments strongly verified that the combination of temsirolimus with polymeric CA4-NPs exhibited an additive toxicity to 4T1 cells. An in vivo study with the 4T1 mammary adenocarcinoma model revealed that consistent with the proposed scenario, combination therapy with CA4-NPs plus temsirolimus suppressed tumor growth significantly more strongly compared to either CA4-NPs or temsirolimus monotherapy, and the inhibition rate to 4T1 tumor with a volume of 300 mm3 was 71%. The mechanism underling combination treatment was confirmed by western blotting and immunofluorescence staining, and the results demonstrated that temsirolimus could inhibit HIF1α expression. Thus, this work provides a mechanistic rationale for the use of VDAs in combination with the mTOR inhibitor to enhance anticancer efficacy, delaying tumor recurrence and inhibiting tumor metastasis.
研究领域:
肿瘤学
·
药理学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2023
·Vol. 6
·期 4
·2200304
·
IF 4.6
Dan Zhao,Min Wu,Yanan Tian,Lu Gao,Fu Wang
With the advantages of ferroptosis therapy (FT) in solving the apoptotic resistance of tumors, a smart strategy based on the combination of glucose oxidase (GOx) and ferroptosis-inducing nanoagents is proposed to boost the FT. However, most of the nanoagents remain limited in complex synthesis, poor targeting specificity, and unclarified biological mechanisms. Herein, a multifunctional nanoplatform based on fluorescent apoferritin-gold nanoclusters combined with GOx (AFt-AuNCs@GOx) is designed for tumor-targeted imaging and FT. The results show that AFt-AuNCs@GOx catalyze the generation of toxic ·OH from H 2 O 2 supplied by GOx. Consequently, AFt-AuNCs@GOx induce the enhanced ferroptosis effect in 4T1 cells. Additionally, the transcriptome assay of 4T1 cells identifies the differential expression genes related to ferroptosis process after AFt-AuNCs@GOx treatment. Moreover, with the merit of intrinsic fluorescence, the biodistribution both in vitro and in vivo of AFt-AuNCs@GOx can be effectively visualized. In vivo evidences reveal that AFt-AuNCs@GOx have the desired efficacy of FT and excellent biosafety. Overall, the AFt-AuNCs@GOx nanoplatform offer remarkable advantages in simple architecture, fluorescent imaging, precise targeting, and tumor inhibition. The exploration of the ferroptosis effect and biological mechanisms of AFt-AuNCs@GOx, as well as its application in tumor therapy, can introduce a new insight into the field of ferroptotic nanomedicine.
研究领域:
纳米技术
·
癌症治疗
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分子生物学
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2017
·
IF 6.319
Jing Wang,Lifei Xie,Tao Wang,Fengxin Wu,Jie Meng,Jian Liu,Haiyan Xu
Cationic macromolecules are attractive for use as small interfering RNA (siRNA) carriers due to their performance in non-immunological reactions, customization during synthesis, and low costs compared to viral carriers. However, their low transfection efficiency substantially hinders their application in both clinical practices and academic research, which is mostly attributable to the low capacity of siRNA/cationic macromolecule complexes to escape lysosomes . To address this challenge, we designed an amphiphilic fullerene derivative (C 60 -Dex-NH 2 ) for efficient and controllable siRNA delivery. To synthesize C 60 -Dex-NH 2 , terminally aminated dextran was conjugated to C 60 . The conjugate was further cationized by covalently introducing ethylenediamine to the dextran. The physicochemical characteristics of C 60 -Dex-NH 2 was examined with elemental analyses, gel permeation chromatography , solid-state nuclear magnetic resonance ( 13 C, HPDEC), agarose gel electrophoresis , and dynamic light scattering . The cytotoxicity, cellular uptake, intracellular distribution , and in vitro RNA interference (RNAi) of siRNA/C 60 -Dex-NH 2 complex was evaluated in the human breast cancer cell line MDA-MB-231. The RNAi efficiencies mediated by C 60 -Dex-NH 2 in vivo was evaluated in subcutaneous tumor-bearing mice. The results showed that C 60 -Dex-NH 2 has a specific amphiphilic skeleton and could form micelle-like aggregate structures in water, which could prevent siRNA from destroying by reactive oxygen species (ROS). When exposed to visible light, C 60 -Dex-NH 2 could trigger controllable ROS generation which could destroy the lysosome membrane, promote the lysosomal escape, and enhance the gene silencing efficiency of siRNA in vitro and in vivo . The gene silencing efficiency could reach a maximum of 53% in the MDA-MB-231-EGFP cells and 69% in the 4T1-GFP-Luc2 tumor-bearing mice. Statement of Significance We designed a novel photosensitive amphiphilic carrier (C 60 -Dex-NH 2 ) for efficient and controllable siRNA delivery, which can be used in gene therapy. We showed that C 60 -Dex-NH 2 could destroy lysosome membrane via controllable generation of ROS when exposed to light, which can help siRNA to escape from lysosome before degradation. This can enhance the gene silencing efficiency significantly and provides a useful way to regulate RNAi efficiency by light. One advantage for C 60 -Dex-NH 2 system is C 60 has broad absorbance spectrum and can be activated by weak visible light; Furthermore, C 60 -Dex-NH 2 has a specific amphiphilic structure, which may prevent siRNA from degrading and allows C 60 -Dex-NH 2 to embed into the lipid membrane of lysosome to improve the ROS induced lysosomal disturbance after internalization .
研究领域:
药学
·
纳米技术
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Yanzhi Wang,Cancan Sun,Leaf Huang,Mengqian Liu,Lu Li,Xiping Wang,Linchao Wang,Shanshan Sun,Haiwei Xu,Gege Ma,Lei Zhang,Jiaxin Zheng,Hongmin Liu
The potential of combination therapy using nanoparticle delivery systems in improving triple-negative breast cancer treatment efficacy remains to be explored. Here, we report a novel nanoparticle system using a cholesterol biguanide conjugate hydrochloride (CBH) as both a drug and carrier to load magnolol (MAG). Poly(ethylene glycol)-poly(lactic-co-glycolic acid) (mPEG-PLGA) and aminoethyl anisamide-poly(ethylene glycol)-poly(lactic-co-glycolic acid) (AEAA-PEG-PLGA) were added to form nanoparticles. Nanoparticles accumulated most in tumor tissues when the weight ratio of AEAA-PEG-PLGA to mPEG-PLGA was 4:1. MAG and CBH exerted a synergistic inhibitory effect on 4 T1 cells. An in vitro study showed that nanoparticles displayed the highest tumor cell uptake rate, highest apoptosis rate, and strongest inhibitory effect on tumor cell migration and monoclonal formation. CBH might promote nanoparticle uptake by cells and lysosomal escape. After intravenous administration to mice with 4 T1 breast tumors in situ , the nanoparticles inhibited tumor growth without obvious toxicity. Western blot results showed that nanoparticles altered the levels of p53, p-AKT, and p-AMPK in the tumor tissue. Moreover, cell apoptosis was found in the same area of H&E-stained and TUNEL-stained tumors treated with the nanoparticles. Collectively, this nanoparticle system provides a novel combination drug delivery strategy for treating triple-negative breast cancer.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2022
·
IF 6.819
Guolian Ren,Yujie Li,Canqi Ping,Danyu Duan,Ning Li,Jiaqi Tang,Rongrong Wang,Wenju Guo,Xiaomin Niu,Qiuyue Ji,Guoshun Zhang,Ruili Wang,Shuqiu Zhang
To realize the synergistic anti-tumor effect of chemotherapy and photodynamic therapy, the mono sulfide-modified docetaxel (DTX) prodrugs (DSD) provided by our laboratory and hematoporphyrin (HP) were used to physically prepare co-assembled nanoparticles (DSD/HP NPs) by nano-precipitation. For the first time, this study showed its characteristics, in vitro anti-tumor activity, pharmacokinetic behavior in rats, in vivo distribution, and pharmacodynamic effects on 4T1 tumor-bearing Bal b/c mice. DSD/HP NPs optimized by single-factor and response surface optimization had several distinct characteristics. First, it had dark purple appearance with particle size of 105.16 ± 1.24 nm, PDI of 0.168 ± 0.15, entrapment efficiency and drug loading of DSD and HP in DSD/HP NPs of 96.27 ± 1.03% and 97.70 ± 0.20%, 69.22 ± 1.03% and 20.03 ± 3.12%, respectively. Second, it had good stability and could release DTX and HP slowly in the media of pH 7.4 PBS with 10 mM DTT (H2O2). Moreover, DSD/HP NPs along with NiR treatment significantly inhibited 4T1 cells proliferation, and induced more reactive oxygen species and cells apoptosis. In vivo pharmacokinetic and pharmacodynamic studies showed that DSD/HP NPs could prolong the drug circulation time in rats, increase drug distribution in tumor site, obviously inhibit tumor growth, and decrease the exposure of drug to normal tissues. Therefore, DSD/HP NPs as a promising co-assembled nano-drug delivery system could potentially improve the therapeutic efficiency of chemotherapeutic drug and achieve better anti-tumor effects due to the combination of chemotherapy and photodynamic therapy.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
生物医学工程
✓ 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）