Pharmaceutics
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2024
·Vol. 16
·期 12
·1609
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IF 4.9
Xiaoli Zhang,Tingting Li,Jindong Tong,Meihong Zhou,Zi Wang,Xingdang Liu,Wei Lu,Jingjing Lou,Qingtong Yi
Background/Objectives: The purpose of this study was to develop the gemcitabine-loaded drug-eluting beads (G-DEBs) for transarterial chemoembolization (TACE) in rabbit renal tumors and to evaluate their antitumor effect using 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/X-ray computed tomography (18F-FDG PET/CT). Methods: DEBs were prepared by polyvinyl alcohol-based macromer crosslinked withN-acryl tyrosine andN,N′-methylenebis(acrylamide). Gemcitabine was loaded through ion change to obtain G-DEBs. Their particle size and drug release profile were characterized. VX2 tumors were implanted in the right kidney of rabbits to establish the renal tumor model. The tumor-bearing rabbits received pre-scan by18F-FDG PET/CT, followed by targeted transarterial injection of G-DEBs under digital subtraction angiography (DSA) guidance. The rabbits received another18F-FDG PET/CT scan 10 or 14 days after the treatment. The therapeutic effect was further validated by histopathological analysis of the dissected tumors. Results: The average particle size of the microspheres was 58.06 ± 0.50 µm, and the polydisperse index was 0.26 ± 0.002. The maximum loading rate of G-DEBs was 18.09 ± 0.35%, with almost 100% encapsulation efficiency. Within 24 h, GEM was eluted from G-DEBs rapidly and completely, and more than 20% was released in different media. DSA illustrated that G-DEBs were delivered to rabbit renal tumors. Compared with the untreated control group with increased tumor volume and intense18F -FDG uptake, the G-DEBs group showed significant reductions in tumor volume and maximum standard uptake value (SUVmax) 10 or 14 days after the treatment. Histopathological analysis confirmed that the proliferating area of tumor cells was significantly reduced in the G-DEBs group. Conclusions: Our results demonstrated that G-DEBs are effective in TACE treatment of rabbit VX2 renal tumors, and18F-FDG PET/CT provides a non-invasive imaging modality to monitor the antitumor effects of TACE in renal tumors.
研究领域:
肿瘤学
·
影像医学
·
药剂学
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DOI
PubMed
高影响因子
Science Bulletin
·
2022
·
IF 20.577
Shaohua Qu,Qian Jia,Zheng Li,Zhongliang Wang,Li Shang
Near-infrared II (NIR-II) fluorescent nanoprobes hold great potential for biomedical applications. Elucidating the relationship between surface properties of NIR-II nanoprobes and their biological behaviors is particularly important for future probe design and their performance optimization. Despite the rapid development of NIR-II nanoprobes, the distinct role of surface chirality on their biological fates has rarely been exploited. Herein, chiral NIR-II fluorescent Ag 2 S quantum dots (QDs) are synthesized to investigate the relationship between their chirality and biological functions at both in vitro and in vivo levels. D- / L -Ag 2 S QDs exhibit significant differences on their interactions with serum proteins, which further affect the cellular uptake. As a result, D -Ag 2 S QDs can be internalized with higher efficiency (over 2-fold) than that of L -Ag 2 S QDs. Moreover, in vivo studies reveal that the chirality determines the primary localization of these chiral QDs, where a more efficient renal elimination of D -Ag 2 S QDs was observed than that of L -Ag 2 S QDs. Importantly, D -Ag 2 S QDs show preferential accumulation in tumor region than that of L -Ag 2 S QDs in orthotopic kidney tumor model, which points out a new avenue of enhancing targeting capabilities of nanoprobes by engineering their surface chirality.
研究领域:
生物医学工程
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纳米技术
·
分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Wenjing Mo,Shujie Liu,Xiaozhi Zhao,Fayun Wei,Yuhang Li,Xinan Sheng,Wenmin Cao,Meng Ding,Wenlong Zhang,Xiaoqing Chen,Longxiyu Meng,Sheng Yao,Wenli Diao,Hui Wei,Hongqian Guo
Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), two immunosuppressive myeloid components within the tumor microenvironment (TME), represent fundamental barriers in cancer immunotherapy, whereas current nanomedicines rarely exert dual modulatory roles on these cell types simultaneously. Reactive oxygen species (ROS) not only mediates MDSC-induced immunosuppression but also triggers differentiation and polarization of M2-TAMs. Herein, an ROS scavenging nanozyme, Zr-CeO, with enhanced superoxide dismutase- and catalase-like activities for renal tumor growth inhibition is reported. Mechanistically, intracellular ROS scavenging by Zr-CeO significantly attenuates MDSC immunosuppression via dampening the unfolded protein response, hinders M2-TAM polarization through the ERK and STAT3 pathways, but barely affects neoplastic cells and cancer-associated fibroblasts. Furthermore, Zr-CeO enhances the antitumor effect of PD-1 inhibition in murine renal and breast tumor models, accompanied with substantially decreased MDSC recruitment and reprogrammed phenotype of TAMs in the tumor mass. Upon cell isolation, reversed immunosuppressive phenotypes of MDSCs and TAMs are identified. In addition, Zr-CeO alone or combination therapy enhances T lymphocyte infiltration and IFN- γ production within the TME. Collectively, a promising strategy to impair the quantity and function of immunosuppressive myeloid cells and sensitize immunotherapy in both renal and breast cancers is provided.
研究领域:
癌症免疫治疗
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纳米医学
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免疫学
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肿瘤微环境
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产品关联
DOI
PubMed
高影响因子
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