Acta Biomaterialia
·
2023
·
IF 9.7
Qiying Lv,Kai Chi,Xiaolei Shi,Miaodeng Liu,Xiaoye Li,Cheng Zhou,Lin Shi,Huiling Fan,Huan Liu,Jia Liu,Yan Zhang,Shuai Wang,Lin Wang,Zheng Wang
Selectively generating active free radical (AFR) in tumor microenvironment (TME) can promote irreversible oxidation of biomolecules and damage tumor cells, resulting in effective tumor inhibition. However, therapeutic efficacy of AFR-based tumor suppression approaches is often limited by insufficient amount of H 2 O 2 or O 2 within TME. To overcome this obstacle, we design a pH/photothermal dual responsive nanosystem ( [email protected] ) for combined photothermal and nanocatalytic therapy in the near-infrared biowindow. Here the Fe single-atom dispersed N, S-doped carbon nanosheets (FeSA) nanozyme is dispersed by phospholipid-polyethylene glycol-amine (DSPE-PEG-NH 2 ), and further loads artesunate (AS) via an amide reaction. Upon 808-nm laser irradiation in TME, the AS is released and further be catalyzed by the FeSA nanozyme to produce cytotoxic C-centered AFRs, and further be accelerated due to the photothermal conversion performance of FeSA (23.35%). The nanocatalytic process of FeSA nanozyme is realized by density functional theory (DFT). The tumor inhibition rates of a CT26 xenograft model is 92% through a photothermal-enhanced nanocatalytic synergistic therapy, and negligible systematic toxicity is observed. This work offers a potential paradigm of multifunctional single atomic catalysts (SACs) for enhancing tumor nanocatalytic therapy. Statement of significance We designed a pH/photothermal dual responsive nanosystem ( [email protected] ) for nanocatalytic therapy: (1) the nanosystem responsively releases AS under 808-nm laser irradiation in TME; (2) FeSA in the nanosystem can act as heme mimetic to convert AS into high cytotoxic C-centered free radicals for nanocatalytic therapy; (3) the photothermal conversion performance of FeSA further enhances the catalytic process to yield abundant AFR. Both in vitro and in vivo results demonstrate that this nanosystem can efficiently inhibit tumor growth through a photothermal-enhanced nanocatalytic synergistic therapy.
研究领域:
癌症治疗
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纳米技术
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光热疗法
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2022
·
IF 5.364
Nan Zhang,Jing Li,Wenxia Gao,Wangwei Zhu,Jianqin Yan,Ziyun He,Li Li,Fang Wu,Yuji Pu,Bin He
The combined delivery of chemotherapeutics with checkpoint inhibitors of the PD-1/PD-L1 pathway provides a new approach for cancer treatment. Small-molecule peptide inhibitors possess short production cycle, low immunogenicity, and fewer side effects; however, their potential in cancer therapy is hampered by the rapid biodegradation and a nanocarrier is needed for efficient drug delivery. Herein, anticancer drug doxorubicin (DOX) and PD-L1 inhibitor peptide P-12 are co-loaded by a lipid polymer nanocomplex based on poly(lactic-co-glycolic acid) (PLGA) and DSPE-PEG. Octaarginine (R8)-conjugated DSPE-PEG renders the LPN efficient internalization by cancer cells. The optimal nanomedicine LPN-30-R82K@DP shows a diameter of 125 nm and a DOX and P-12 loading content of 5.0 and 6.2%, respectively. LPN-30-R82K@DP exhibits good physiological stability and enhanced cellular uptake by cancer cells. It successfully induces immunogenic cell death and PD-L1 blockade in CT26 cancer cells. The in vivo antitumor study further suggests that co-loaded nanomedicine efficiently suppresses CT26 tumor growth and elicits antitumor immune response. This study manifests that lipid polymer nanocomplexes are promising drug carriers for the efficient chemo-immunotherapy of cancer.
研究领域:
药学
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生物医学工程
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肿瘤学
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药物递送系统
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免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chemosensors
·
2024
·Vol. 12
·期 8
·166
·
IF 3.7
Xiangfang Lin,Qinhui Dong,Yalin Chang,Shusheng Zhang,Pengfei Shi
Luminescent Ag nanoclusters (Ag NCs) are a promising probe material for sensing and bioimaging applications. However, the intrinsic obstacle of poor water stability and photostability greatly restrict their practical application in biological systems. Herein, we report the intracellular hypochlorite (ClO−) detection with amphiphilic copolymer-modified luminescent Ag NCs with good biocompatibility and photostability. The Ag NCs were synthesized by using chemically inert hydrophobic ligands and then modified with an amphiphilic (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000]) (DSPE-PEG-2000) and sodium dodecyl sulfonate (SDS) for phase transfer. It was found that the approach of the removal of organic solvents during the phase transfer has remarkable influences on the properties of the Ag NCs, including their size, luminescence property, and aqueous stability. Furthermore, the silver core of Ag NCs could be oxidatively damaged by ClO−, thereby causing photoluminescence (PL) quenching. The ClO−-induced PL quenching was specific over the other common reactive oxygen species (ROS) as well as some common interferences. Finally, they have been successfully applied as a fluorescent nanoprobe for detecting exogenous and endogenous ClO−in living cells.
研究领域:
纳米技术
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分析化学
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生物化学
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材料科学
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生物传感
✓ 已验证
DOI
高影响因子
Materials Today
·
2023
·
IF 24.2
Xiao-Kang Jin,Jun-Long Liang,Shi-Man Zhang,Qian-Xiao Huang,Shun-Kang Zhang,Chuan-Jun Liu,Xian-Zheng Zhang
Owing to the deficiency of infiltrating immune cells and the accumulation of immunosuppressive cells in tumor microenvironment (TME), immunotherapy remains enormous challenges in colorectal cancer (CRC). Here, CRC was found to be sensitive to cuproptosis which could further evoke immune responses and mediate immune resistance. Thus, a cuproptosis-mediated immunotherapy nanoreactor (CCJD-FA) was constructed by encapsulating copper-based shell-coated CaO 2 and bromodomain-containing protein 4 inhibitor JQ-1 with DSPE-PEG-FA. Within tumor cells, CCJD-FA was disassembled under GSH environment, and the exposed CaO 2 could generate H 2 O 2 under the acidic condition, which reacted with the released Cu 2+ via Fenton-like reaction to produce O 2 for relieving hypoxia and Cu + for inducing cuproptosis. Furthermore, CCJD-FA could also inhibit intracellular glycolysis and ATP generation, then blocking the Cu + efflux protein ATP7B. Meanwhile, the IFN-γ-induced PD-L1 expression could be exactly reduced by the BRD4 suppression and oxygen supply. These effects sensitized cancer cells to cuproptosis, further evoking systemic immune responses and reshaping immunosuppressive TME to inhibit tumor growth.
研究领域:
肿瘤学
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免疫学
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纳米技术
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-21
·
IF 10.6
Chen Shang,He Yan,Huang Xin,Shen Yao,Zou Qingshuang,Yang Gun,Fu Li,Liu Quan,Luo Dixian
Tumor-associated macrophages (TAMs) are a promising target for cancer immunotherapy, but delivering therapeutic agents to TAMs within the tumor microenvironment (TME) is challenging. In this study, a photosensitive, dual-targeting nanoparticle system (M.RGD@Cr-CTS-siYTHDF1 NPs) was developed. The structure includes a shell of DSPE-modified RGD peptides targeting integrin receptors on tumor cells and carboxymethyl mannose targeting CD206 receptors on macrophages, with a core of chitosan adsorbing m6A reading protein YTHDF1 siRNA and chromium nanoparticles (Cr NPs). The approach is specifically designed to target TAM and cancer cells, utilizing the photothermal effect of Cr NPs to disrupt the TME and deliver siYTHDF1 to TAM. In experiments with tumor-bearing mice, M.RGD@Cr-CTS-siYTHDF1 NPs, when exposed to laser irradiation, effectively killed tumor cells, disrupted the TME, delivered siYTHDF1 to TAMs, silenced the YTHDF1 gene, and shifted the STAT3-STAT1 equilibrium by reducing STAT3 and enhancing STAT1 expression. This reprogramming of TAMs towards an anti-tumor phenotype led to a pro-immunogenic TME state. The strategy also suppressed immunosuppressive IL-10 production, increased expression of immunostimulatory factors (IL-12 and IFN-γ), boosted CD8 + T cell infiltration and M1-type TAMs, and reduced Tregs and M2-type TAMs within the TME. In conclusion, the dual-targeting M.RGD@Cr-CTS-siYTHDF1 NPs, integrating dual-targeting capabilities with photothermal therapy (PTT) and RNA interference, offer a promising approach for molecular targeted cancer immunotherapy with potential for clinical application. Graphical Abstract
研究领域:
癌症生物学
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纳米技术
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免疫疗法
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2018
·
IF 7.877
Jia Song,Chuchu Lin,Xuan Yang,Yanqi Xie,Ping Hu,Huatian Li,Wenbo Zhu,Haiyan Hu
Mitochondria are ideal anti-tumor target due to mitochondria's central regulation role in cell apoptosis and tumor resistance to apoptosis. There are several challenges for mitochondrial targeting drug delivery, including complex multistep preparations, low drug- loading and systemic toxicity from the carriers. To address these issues, we firstly constructed mitochondria-targeting nanodrugs self-assembled from 9-O-octadecyl substituted berberine derivative (BD) using simple nano-precipitation approach. BD-based nanodrugs were modified by DSPE-PEG2000 (distearylphosphatidylethanolamine- methoxypolyethylene glycol 2000) to increase stability. Negatively charged hyaluronic acid (HA) was further coated to conceal positive charges and achieve tumor targeting. PEG and HA dually modified BD NDs (HA/PEG/BD NDs) were prepared with surface charge of −25.8 mV and high drug loading >70%. The degradation of HA by hyaluronidase (HAase) at tumor tissue allowed the exposure of the positively charged PEG/BD NDs to the cells, which is beneficial for cell uptake and further lysosome escape and mitochondrial targeting. Then, HA/PEG/BD NDs were investigated to induce apoptosis through dissipating mitochondria membrane potential, releasing cytochrome C , increasing the activities of caspase 9/3, activating the pro-apoptotic Bax, suppressing the anti-apoptotic Bcl-2 and upregulating ROS levels. In the A549 xenografted tumor model, HA/PEG/BD NDs exhibited obvious tumor cell mitochondrial targeting and significant anti-tumor efficacy. Overall, comparing to conventional nanoparticles , mitochondrial targeting HA/PEG/BD NDs provide a new strategy for cancer treatment with enhanced drug-loading, relatively simplified preparation processes and reduced carrier toxicities.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
分子生物学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Xiao-Shuai Zhang,Kai Cheng,Jian-Shuang Wei,Zhuo-Yao Huang,Xiao-Lin Hou,Yong-Guo Hu,Xiao-Quan Yang,Fang Zhang,Xing Sun,Wei Chen,Bo Liu,Yuan-Di Zhao
In this paper, a mixture of lecithin, polyethylene glycol monostearate, and polyethylene glycol phospholipid (DSPE-PEG 2000 ) is used to wrap hydrophobic nano silver sulfide (Ag 2 S) and 3 ∼ 5 nm ultra-small gold nanoparticle (mAu) to form ∼ 150 nm hydrophilic nanocomposite probe Ag 2 S/ [email protected] 2000 (ASAuDP) with good stability and dispersion. The probe combines the functions of Ag 2 S and mAu, while mAu can significantly inhibit the fluorescence (FL) of Ag 2 S, thereby reducing the phototoxicity of probe when circulating in the body. When the ASAuDP probe is phagocytosed by tumor cell, Ag 2 S and mAu are separated due to the rupture of probe, thereby restoring the ability of FL imaging and ROS production. MTT test, blood analysis and organ pathology test prove that ASAuDP is a safe probe. In vitro and in vivo imaging experiments prove that the ASAuDP probe presents good FL, CT and photoacoustic imaging capabilities. In vitro and in vivo treatments prove that the ASAuDP probe has both photothermal and sonodynamic therapy abilities, and the synergy between them has the best therapeutic effect. Therefore, ASAuDP probe is a kind of integrated diagnostic and therapeutic probe with good safety, and it has a good application prospect in the treatment of tumor.
研究领域:
纳米技术
·
癌症研究
·
生物医学工程
·
材料科学
·
诊疗学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2023
·
IF 15.1
Qing Zheng,Hanghang Liu,Hao Zhang,Yaobao Han,Jiaxin Yuan,Tingting Wang,Yifan Gao,Zhen Li
Mitochondrial dysfunction of neurons is the core pathogenesis of incurable Parkinson's disease (PD). It is crucial to ameliorate the mitochondrial dysfunction of neurons for boosting the therapy of PD. Herein, the remarkable promotion of mitochondrial biogenesis to ameliorate mitochondrial dysfunction of neurons and improve the treatment of PD by using mitochondria-targeted biomimetic nanoparticles, which are Cu 2- x Se-based nanoparticles functionalized with curcumin and wrapped with DSPE-PEG 2000 -TPP-modified macrophage membrane (denoted as CSCCT NPs), is reported. These nanoparticles can efficiently target mitochondria of damaged neurons in an inflammatory environment, and mediate the signaling pathway of NAD + /SIRT1/PGC-1 α /PPAR γ /NRF1/TFAM to alleviate 1-methyl-4-phenylpyridinium (MPP + )-induced neuronal toxicity. They can reduce the mitochondrial reactive oxygen species, restore mitochondrial membrane potential (MMP), protect the integrity of mitochondrial respiratory chain, and ameliorate mitochondrial dysfunction via promoting mitochondrial biogenesis, which synergistically improve the motor disorders and anxiety behavior of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice. This study demonstrates that targeting mitochondrial biogenesis to ameliorate mitochondrial dysfunction has a great potential in the treatment of PD and mitochondria-related diseases.
研究领域:
神经科学
·
纳米技术
·
药理学
·
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）