JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Xuan Li,Hanchen Zhang,Zheng Cao,Haihua Xiao,Chao Weng,Qingfeng Zheng
The clinical efficacy of platinum-based chemotherapeutics, such as cisplatin, has been compromised by the prevalent emergence of drug resistance. This has propelled the search for alternative metal-based anti-tumor agents. Herein, we introduce PolyRu, a novel amphiphilic polymer containing a ruthenium complex and thioketal bonds in its main chain, for lung cancer treatment. PolyRu can self-assemble into nanoparticles (NP@PolyRu) in aqueous solutions and degrade within the reactive oxygen species-rich tumor microenvironment. The ruthenium complex in PolyRu specifically targets mitochondria and induces cancer cell apoptosis. The efficacy of NP@PolyRu was validated in a patient-derived xenograft model of human lung cancer, where NP@PolyRu significantly suppressed tumor progression with favorable biocompatibility，and showed excellent anti-tumor immune effect. NP@PolyRu emerges as a promising candidate for addressing cancer drug resistance, signifying a substantial leap forward in the realm of metal polymer-based cancer therapeutics.
研究领域:
肿瘤学
·
药理学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2022
·
IF 5.518
Yuguang Yang,Wei Cui,Jie Zhao
Drug resistance is the main challenge in cancer treatment by chemotherapy. To overcome the problems, photodynamic therapy (PDT) can be introduced to increase the internalization of chemotherapeutics. Herein, we design and fabricate core-shell nanostructures for the increased therapy effect of drug resistant cancers. Human serum albumin (HSA) is conjugated with Rose Bengal (RB) (HSA-RB) to improve the endocytosis efficiency of the photosensitizer . Then we fabricated a core-shell nanostructure by coating with doxorubicin (DOX)-loaded CaCO 3 (CaCO 3 @DOX) with HSA-RB and dialdehyde carboxymethyl cellulose (DCMC) via a layer-by-layer technique. The formed CaCO 3 @DOX@(HSA-RB/DCMC) n nanostructures can be easily endocytosed by DOX resistant cancer cells (MCF-7/ADR) in the presence of low dose PDT, and greatly prevent the proliferation of cancer cells by the synergistic effect of PDT and chemotherapy. The nanostructures present efficient methods to solve drug resistance problems in the cure of cancers.
研究领域:
肿瘤学
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药理学
·
生物医学工程
✓ 已验证
DOI
高影响因子
npj Breast Cancer
·
2024
·Vol. 10
·期 1
·1-15
·
IF 6.5
Rossetti Stefano,Broege Aaron,Sen Adrish,Khan Salmaan,MacNeil Ian,Molden Jhomary,Kopher Ross,Schulz Stephen,Laing Lance
The PI3K, AKT, and mTOR (PAM) pathway is frequently dysregulated in breast cancer (BC) to accommodate high catabolic and anabolic activities driving tumor growth. Current therapeutic options for patients with hormone receptor (HR) + / HER2- advanced BC (ABC) include PAM inhibitors that selectively inhibit only one PAM pathway node, which can lead to drug resistance as cells rapidly adapt to maintain viability. We hypothesized that gedatolisib, which potently inhibits all Class I PI3K isoforms, as well as mTORC1 and mTORC2, may be more effective in BC cells than single-node PAM inhibitors by limiting adaptive resistances. By using multiple functional assays, a panel of BC cell lines was evaluated for their sensitivity to four different PAM inhibitors: gedatolisib (pan-PI3K/mTOR inhibitor), alpelisib (PI3Kα inhibitor), capivasertib (AKT inhibitor), and everolimus (mTORC1 inhibitor). Gedatolisib exhibited more potent and efficacious anti-proliferative and cytotoxic effects regardless of the PAM pathway mutational status of the cell lines compared to the single-node PAM inhibitors. The higher efficacy of gedatolisib was confirmed in three-dimensional culture and in BC PDX models. Mechanistically, gedatolisib decreased cell survival, DNA replication, cell migration and invasion, protein synthesis, glucose consumption, lactate production, and oxygen consumption more effectively than the other PAM inhibitors tested. These results indicate that inhibition of multiple PAM pathway nodes by a pan-PI3K/mTOR inhibitor like gedatolisib may be more effective at inducing anti-tumor activity than single-node PAM inhibitors. A global Phase 3 study is currently evaluating gedatolisib plus fulvestrant with and without palbociclib in patients with HR+/HER2− ABC.
研究领域:
肿瘤学
·
分子生物学
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药理学
✓ 已验证
DOI
高影响因子
DYES AND PIGMENTS
·
2023
·
IF 4.5
Huifang Yao,Xiaobo Xiong,Feng Wu,Xiangyang Hu
The general mechanism of chemotherapeutic resistance is related to changes in the uptake and efflux rate of chemotherapeutic drugs or intracellular transport. In the progress of photodynamic and PTX combination therapy, the excessive use of photosensitizers (PSs) may cause side effects. Since PSs are exposed to light, they can still cause ongoing damage to normal cells. To effectively reduce this side effect, we propose a strategy to regulate the concentration of PTX in resistant cells using low concentrations of AIEgen PSs. In this work, the molecular structure of four AIEgen PSs ( TPEPy , TPECPy , TPAPy , and TPESPy ) were designed and synthesized featuring different “D−π−A” type structures. They displayed excellent optical properties , good biocompatibility , good PDT effect, mitochondrial targeting and cell imaging . Among these AIEgen PSs, TPESPy exhibited the strongest PDT effect in tumor cells and PTX resistant tumor cells. The reversal coefficient of PTX resistant tumor cells can be achieved as 2214. In addition, to demonstrate the transport mechanism of PTX within tumor cells, we further study the effect of uptake and expel PTX in the PTX resistant SKOV-3 cells. The results show the rate of uptake and expel PTX for PTX resistant SKOV-3 cells can be effectively changed by controlling the concentration of AIEgen PSs and light irradiation time, providing precise treatment options for drug-resistant tumor cells.
研究领域:
生物化学
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肿瘤学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-18
·
IF 15.7
Zhou Zhilan,Liu Yichang,Wang Ya,Jiang Hang,Chen Tingting,Zhu Yingdi,Fu Ting,Li Juan
Receptor tyrosine kinases (RTKs) play a crucial role in the regulation of intracellular signal transduction, underscoring their significance as targets for drug therapy. Despite the widespread clinical use of kinase inhibitors, the increasing occurrence of off-target effects and drug resistance makes it urgent to explore alternative approaches to modulate RTKs functions. Here, we propose an approach for attenuating cell-surface receptor signaling, termed Aptamer-directed Phosphatase Recruiting Chimeras (Apt-PRCs). The Apt-PRC is composed of an aptamer to recruit phosphatases and a binder to target receptors. As a proof-of-concept, we design and construct Apt-PRCs intended for direct dephosphorylation of tyrosine residues on the receptor targets, i.e ., epidermal growth factor receptor and mesenchymal-epithelial transition factor, respectively. The as-developed Apt-PRCs manage to inhibit specifically and efficiently the reception and transmission of phosphorylation signals both in vitro and in vivo. Furthermore, it is discovered that the induced dephosphorylation could enhance the susceptibility to gefitinib in drug-resistant cancer cells and a xenograft mouse model, indicating the potential of Apt-PRCs to overcome drug resistance in cancer. This work offers a versatile methodology to design molecular mediators to modulate receptor phosphorylation so as to regulate the downstream signal transduction and overcome drug resistance.
研究领域:
分子生物学
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癌症研究
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 31
·6439-6447
·
IF 4.726
Ai-Zheng Chen,Yong-Qiang Kang,Shi-Bin Wang,Na Tang,Xiao-Qian Su
The co-delivery of siRNA and therapeutic agents provides an effective method for cancer chemotherapy by avoiding drug resistance during the treatment. With a combination of ionic gelation and supercritical fluid technology, nanoparticle-embedded composite microparticles (CMPs) co-loaded with siRNA and paclitaxel (siRNA-PTX-CMPs) were successfully prepared. The results show that CMPs embedded with nanoparticles with a diameter of 50–100 nm exhibited a spherical shape and core–shell structure with a mean diameter of 323 nm. The encapsulation efficiency of siRNA in chitosan nanoparticles (CS NPs) was 96.97%. The drug load and encapsulation efficiency of PTX-loaded CMPs (5% dosage) were 1.40% and 27.95%, respectively; both these increased with an increase in dosage. It was found that no change had occurred in the functional groups of the components during the supercritical process, while the physical form of PTX had shifted to an amorphous state. In the cell experiments, the CMPs clustered around the nucleus after being taken up by the Bcap-37 cells. The results of the antitumor effect experiments revealed that the co-loaded siRNA-PTX-CMPs achieved a significantly better synergistic effect than single dosages, which indicated that the co-delivery system developed by the supercritical process could have potential in the application of cancer chemotherapy.
研究领域:
药剂学
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肿瘤学
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药物递送系统
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生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF CANCER
·
2024
·
IF 5.7
Jiaxin Ren,Cheng Zhao,Ruizhu Sun,Jian Sun,Laiya Lu,Jun Wu,Shuaijun Li,Lei Cui
Due to the lack of a precise in vitro model that can mimic the nature microenvironment in osteosarcoma, the understanding of its resistance to chemical drugs remains limited. Here, we report a novel three-dimensional model of osteosarcoma constructed by seeding tumor cells (MG-63 and MNNG/HOS Cl no. 5) within demineralized bone matrix scaffolds. Demineralized bone matrix scaffolds retain the original components of the natural bone matrix (hydroxyapatite and collagen type I), and possess good biocompatibility allowing osteosarcoma cells to proliferate and aggregate into clusters within the pores. Growing within the scaffold conferred elevated resistance to doxorubicin on MG-63 and MNNG/HOS Cl no. 5 cell lines as compared to two-dimensional cultures. Transcriptomic analysis showed an increased enrichment for drug resistance genes along with enhanced glutamine metabolism in osteosarcoma cells in demineralized bone matrix scaffolds. Inhibition of glutamine metabolism resulted in a decrease in drug resistance of osteosarcoma, which could be restored by α-ketoglutarate supplementation. Overall, our study suggests that microenvironmental cues in demineralized bone matrix scaffolds can enhance osteosarcoma drug responses and that targeting glutamine metabolism may be a strategy for treating osteosarcoma drug resistance. What's new? Osteosarcoma resistance to chemical drugs remains poorly understood. Here, the authors constructed a novel three-dimensional osteosarcoma model by seeding tumor cells within demineralized bone matrix scaffolds. Growing within the scaffold conferred elevated doxorubicin resistance to osteosarcoma cells when compared to two-dimensional cultures. Osteosarcoma cells in demineralized bone matrix scaffolds displayed an increased enrichment for drug resistance genes along with enhanced glutamine metabolism. This model could help better understand the complex cell–matrix interactions between osteosarcoma cells and surrounding native bone and potentially screen novel effective chemotherapies to treat osteosarcoma.
研究领域:
肿瘤学
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细胞生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Nanoscience and Nanotechnology Letters
·
2017
·Vol. 9
·期 1
·77-80
·
IF 1.889
Chen Cong,Tang Shijia,Hu Ke
Tumor stem cell (TSC) was one of the research hotspots in tumor diagnostics. However, cells with high expression of TSCs-related markers were rare when they were cultured in 2D models. It is important to build in vitro tumor models to enhance the proliferation of cells with TSCs
related markers. In this study, the magnetic hydrogel based on magnetic nanoparticle assemblies was applied as the substrate for glioma tumor cell (U251) culture. Tumor cells on the surface of this composite material preferred to form multicellular spheroids through adhesion, migration and
emergence. The enhanced expression of TSCs markers indicated the enrichment of TSCs and the stem cell characters of U251 cells cultured on magnetic hydrogel which were further confirmed by drug resistance assay. This composite might provide a valuable platform for TSCs-relative mechanism research
and anti-cancer treatment.
研究领域:
生物材料学
·
肿瘤学
·
细胞生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2024
·
IF 3.6
Qing Yang,Xiaosheng Jin,Yuansen Zhang,Xiaoqiu Wu,Haiying Lin,Tingting Ji,Rongzhou Li
The aim of this study is to investigate the impact of sh-LncRNA ASB16-AS1 on doxorubicin (DOX) resistance in colorectal cancer (CRC). First, an in vitro study was conducted to investigate the effects of LncRNA ASB16-AS1, miR-185-5p, and TEAD1 on drug resistance in CRC cells. Subsequently, utilizing nanotechnology, poly(beta amino esters) (PBAE)/zeolitic imidazolate framework-8 (ZIF-8)@sh-LncRNA ASB16-AS1 nanoparticles (PZSNP) were synthesized and characterized, evaluating their cellular toxicity and hemolytic activity. Finally, a mouse subcutaneous tumor model was established by subcutaneous injection of SW480/DOX cell suspension to investigate the impact of PZSNP on the tumor. Under DOX treatment, downregulation of LncRNA ASB16-AS1, overexpression of miR-185-5p, or downregulation of TEAD1 suppressed the viability and proliferation of drug-resistant CRC cells while promoting apoptosis. Conversely, overexpression of LncRNA ASB16-AS1, inhibition of miR-185-5p, or overexpression of TEAD1 enhanced the viability and proliferation of drug-resistant CRC cells while inhibiting apoptosis. The synthesized PZSNP exhibited a spherical shape with an average particle size of 123.6 nm, possessed positive charge, displayed good stability. It effectively encapsulated shRNA and displayed low cellular toxicity and hemolytic activity. Under DOX treatment, significant tumor necrosis was observed in the PZSNP group, and tumor growth was suppressed without causing weight loss. LncRNA ASB16-AS1, miR-185-5p, and TEAD1 are involved in regulating cell viability, proliferation, and apoptosis, contributing to drug resistance in CRC cells. sh-LncRNA ASB16-AS1 enhances the sensitivity of CRC cells to DOX during treatment, and in vivo delivery of PZSNP may serve as an effective strategy to overcome chemotherapy resistance in CRC.
研究领域:
肿瘤学
·
分子生物学
·
纳米技术
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Jin-Xin Huang,Wei-Hua Zhang,Ye-Ming Wu,Jian-Yu Hu,Huan Long,Hai-Dong Zhu,Jian-Qiong Zhang,Gao-Jun Teng,Fei Xiong
Drug-eluting bead transcatheter arterial chemoembolization (D-TACE) is one of the first-line treatment for intermediate hepatocellular carcinoma (HCC). However, the dual hypoxia microenvironment, due to inherent tumor hypoxia and TACE-induced hypoxia, triggers drug resistance in HCC. To address this challenge, the study develops multicavitary microspheres capable of encapsulating oxygen and harnessing magnetic hyperthermia to enhance oxygen permeability. The novel multicavitary oxygen-encapsulated magnetothermal drug-eluting microspheres (OTD-Ms) effectively reduce hypoxia-related proteins (HIF-1α, VEGF-A) and drug resistance (P-gp) both in vitro and in vivo. Moreover, these microspheres demonstrate improved TACE efficacy and enhance survival rates in a rabbit VX-2 tumor model, suggesting their potential for HCC treatment.
研究领域:
肿瘤学
·
介入放射学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2019
·Vol. 17
·期 1
·1-12
·
IF 5.345
Zeng Xiaofan,Wang Qi,Tan Xuan,Jia Le,Li Yuwei,Hu Mingdi,Zhang Zhijie,Bai Xicheng,Zhu Yanhong,Yang Xiangliang
Background Glioma is a common brain tumor with a high mortality rate. A small population of cells expressing stem-like cell markers in glioma contributes to drug resistance and tumor recurrence.Methods Porous silicon nanoparticles (PSi NPs) as photothermal therapy (PTT) agents loaded with TMZ (TMZ/PSi NPs), was combined with hyperbaric oxygen (HBO) therapy in vitro and in vivo. To further investigate underlying mechanism, we detected the expression of stem-like cell markers and hypoxia related molecules in vitro and in vivo after treatment of TMZ/PSi NPs in combination with PTT and HBO.Results NCH-421K and C6 cells were more sensitive to the combination treatment. Moreover, the expression of stem-like cell markers and hypoxia related molecules were decreased after combination treatment. The in vivo results were in line with in vitro. The combination treatment presents significant antitumor effects in mice bearing C6 tumor compared with the treatment of TMZ, PTT or TMZ/PSi NPs only.Conclusion These results suggested the TMZ/PSi NPs combined with HBO and PTT could be a potential therapeutic strategy for glioma.
研究领域:
肿瘤学
·
纳米技术
·
治疗策略
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Haimeng Pei,Haibin Si,Dexin Du,Lu Li,Bo Tang
Extracellular vesicles (EVs) play a crucial role in mediating cell–cell communication and shaping cellular functions. However, the relationship between EVs secretion and cellular drug sensitivity, as well as the role of EVs in drug resistance development, remains unclear. Therefore, characterizing rare drug-resistant cells within cell populations and obtaining time-resolved information on single-cell EVs secretion are essential for understanding EVs’ role in drug resistance. Herein, we utilize a single-cell EVs secretion quantification chip (SCQ-chip) to compartmentalize individual cells and longitudinally monitor their secretion during drug treatment. The results show that EVs secretion is closely related to cellular drug sensitivity and strongly depends on the drug dose. Low-dose drugs induce increased levels of EVs secretion as a protective mechanism, whereas high-dose drugs reduce both cell viability and EVs secretion. Notably, stem-like cells exhibit a unique slow-fluctuating EVs secretion pattern. Furthermore, coculturing drug-sensitive cells with EVs from drug-resistant cells revealed that EVs facilitate drug resistance transfer. Proteomic analysis indicates that this process is primarily driven by metabolism-related pathways, confirming EVs as mediators of drug resistance dissemination. Our results proposed that EVs secretion is a promising indicator for drug resistance analysis, which will inspire us to develop new drugs targeting EVs secretion as a strategy to overcome drug resistance.
研究领域:
分子生物学
·
细胞生物学
·
药理学
·
生物化学
·
癌症研究
✓ 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）