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
·
纳米技术
·
免疫疗法
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 23
·6754-6763
·
IF 6.183
Zhiming Zhang,Li Zhang,Chenlu Huang,Qing Guo,Yueyue Zuo,Nannan Wang,Xu Jin,Linhua Zhang,Dunwan Zhu
Chemophotothermal combination therapy has emerged as a novel and promising strategy to treat cancer. To improve anticancer effectiveness and reduce systemic toxicity, it is essential to trigger drug release at tumor sites or within tumor cells for maximal drug exposure. Herein, we constructed gas-generating mesoporous silica nanoparticles (MSNs) that can load ammonium bicarbonate (ABC) and doxorubicin (DOX) within the pores, encapsulate indocyanine green (ICG) onto the polydopamine (PDA) layer, and modify the RGD peptide on the outer surface [denoted as M(abc)-DOX@PDA-ICG-PEG-RGD] for triggered drug release and targeted chemophotothermal combination therapy. Upon hyperthermia or low pH value, the encapsulated ABC can efficiently generate CO2 gas, thus enhancing the damage to the PDA layer and accelerating DOX release. In vitro experiments showed that the M(abc)-DOX@PDA-ICG-PEG-RGD significantly enhanced cellular uptake and cytotoxicity, and laser irradiation further increased the endocytic and cytotoxic effects. An in vivo study indicated that the nanoparticles can effectively accumulate at the tumor site and significantly inhibited tumor growth with no side-effects to the normal organs. Thus, this gas-generating MSN-based nanocarrier that can trigger drug release in response to laser irradiation or low pH value holds great potential in enhancing cancer chemophotothermal combination therapy.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Weiwei Wu,Yan Yang,Yu Zhang,Yina Zeng,Zhuoying Liang,Xiling Song,Yadong Huang,Wei Xue,Siming Yu
Recently, enzyme dynamic therapy (EDT) has gained enormous attraction in cancer therapy. However, the efficiency of EDT is still largely restricted by the inefficient delivery efficiency of chloroperoxidase (CPO) and the insufficient hydrogen peroxide (H 2 O 2 ) content in the tumor microenvironment (TME). In the present work, a biodegradable cupper peroxide decorated hollow polydopamine nanocomposite (HPDCP) with surface functionalization of PEGlated tumor targeting peptide RGD (PEG-RGD) was designed for effective CPO delivery. The resultant nanosystem of HPDCP@CPO@PEG-RGD displayed high CPO delivery efficiency to breast tumors without comprising the enzyme activity. Moreover, the nanosystem can dissociate rapidly in acidic TME by supplying substantial H 2 O 2 and simultaneously releasing Cu 2+ and CPO, followed by initiating self-activated cascade reactions. At the one hand, the self-supplied H 2 O 2 greatly enhanced the singlet oxygen ( 1 O 2 ) generation via the CPO-mediated enzyme dynamic reaction. At the other hand, substantial hydroxyl radical (•OH) was produced via the Cu 2+ -driven Fenton reaction for chemodynamic therapy (CDT). Therefore, the anticancer efficiency of EDT was significantly enhanced due to the synergistic EDT/CDT effect. Mechanism study revealed that 1 O 2 /•OH generated by HPDCP@CPO@PEG-RGD synergistically inhibited breast cancer cells by firstly causing severe lipid peroxidation, followed by triggering mitochondria-mediated apoptosis and causing irreversible DNA damage by inhibiting the expression of DNA repair enzyme poly (ADP-ribose) polymerase 1 (PARP-1).
研究领域:
癌症治疗
·
纳米技术
·
酶工程
·
材料科学
·
生物化学
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Jianrong Wu,Zheying Meng,Agata A. Exner,Xiaojun Cai,Xue Xie,Bing Hu,Yu Chen,Yuanyi Zheng
Gas therapy as an emerging therapeutic modality for cancer treatment is still facing critical challenges such as precise delivery and controllable release of therapeutic gas. Herein, we report a “tumor-microenvironment remodeling” strategy for in situ sustained release of CO gas and magnetic resonance imaging (MRI)-monitored targeted/synergistic cancer gas/starvation nanotherapy by engineering cascade biodegradable nanocatalyst . The nanocatalyst integrates the enzyme catalyst glucose oxidase (GOD) and H 2 O 2 -sensitive molecule manganese carbonyl (MnCO) entrapped biodegradable hollow mesoporous organosilica nanoparticles (HMONs). Especially, GOD is initially exploited as a gatekeeper, followed by surface engineering with arginine-glycine-aspartic acid (RGD) for specifically targeting α v β 3 integrin-overexpressed cancer cells. The GOD is dissociated under reduced pH to release the loaded MnCO, and sequentially produce gluconic acid and H 2 O 2 to remodel the TME for facilitating the in situ generation of CO/Mn 2+ . As systematically demonstrated both at cellular level and in an animal tumor xenograft model, the engineered nanocatalyst achieves superior theranostics performance via combinatorial CO gas and starving-like nanotherapy. This work provides an effective strategy for augmenting CO-mediated antitumor efficacy by remodeling the tumor microenvironment .
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
材料科学
·
医学成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Zhongxi Xie,Xiaoran Deng,Bei Liu,Shanshan Huang,Pingan Ma,Zhiyao Hou,Ziyong Cheng,Jun Lin,Shifang Luan
Photoinduced reversible addition–fragmentation chain transfer (RAFT) polymerization generally adopts high-energy ultraviolet (UV) or blue light. In combination with photoredox catalyst, the excitation light wavelength was extended to the visible and even near-infrared (NIR) region for photoinduced electron transfer RAFT polymerization. In this report, we introduce for the first time a surface NIR-light-initiated RAFT polymerization on upconversion nanoparticles (UCNPs) without adding any photocatalyst and construct a functional inorganic core/polymer shell nanohybrid for application in cancer theranostics. The multilayer core–shell UCNPs (NaYF4:Yb/Tm@NaYbF4:Gd@NaNdF4:Yb@NaYF4), with surface anchorings of chain transfer agents, can serve as efficient NIR-to-UV light transducers for initiating the RAFT polymerization. A hierarchical double block copolymer brush, consisting of poly(acrylic acid) (PAA) and poly(oligo(ethylene oxide)methacrylate-co-2-(2-methoxy-ethoxy)ethyl methacrylate) (PEG for short), was grafted from the surface in sequence. The targeting arginine–glycine–aspartic (RGD) peptide was modified at the end of the copolymer through the trithiolcarbonate end group. After loading of doxorubicin, the UCNPs@PAA-b-PEG-RGD exhibited an enhanced U87MG cancer cell uptake efficiency and cytotoxicity. Besides, the unique upconversion luminescence of the nanohybrids was used for the autofluoresence-free cell imaging and labeling. Therefore, our strategy verified that UCNPs could efficiently activate RAFT polymerization by NIR photoirradiation and construct the complex nanohybrids, exhibiting prospective biomedical applications due to the low phototoxicity and deep penetration of NIR light.
研究领域:
材料科学
·
生物医学工程
·
高分子化学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY
·
2022
·
IF 6.76
Mengchao Ding,Xiaoying Kong,Weiyan Chen,Lei Yan,He Huang,Zunzhou Lv,Peng Jiang,Ali Mu,Congcong Huang,Jinsheng Shi
Single cancer starvation therapy (ST) strategy can’t achieve satisfactory anti-tumor effect, mainly due to the diversified nutritional sources of tumor cells. Herein, [email protected] 2 @2-Deoxy-D-glucose(2-DG)-CaCO 3 -RGD nanoparticles (CADCR NPs) were prepared for three-pathway blocking for efficient starvation therapy as well as reinforced photothermal therapy (PTT) and chemodynamic therapy (CDT). After CADCR NPs were targeted to tumor cells, CaCO 3 was ruptured in the acidic environment, releasing Ca 2+ to chelate glutamine and cutting off the glutamine metabolic pathway of the tumor. 2-DG was also released from mesoporous SiO 2 and restrained the glycolytic pathway of tumor cells. In addition, under the thermal stimulus of near-infrared irradiation, axitinib was released from CuS NPs, which inhibited the proliferation of tumor blood vessels, ultimately inhibiting the aerobic respiratory pathway of tumor cells. Interestingly, CADCR NPs also showed potential to reshape the tumor microenvironment (TME) and promoted the transformation of macrophages from M2 to M1 type, increasing the expression of CD8+ T cells in the tumor site. In conclusion, CADCR NPs achieve severe tumor starvation by simultaneously interfering with three energy metabolic pathways, and further enhance tumor treatment with the aid of PTT, CDT, and TME improvement, which exhibits great potential for clinical cancer therapy.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
·
肿瘤微环境
·
细胞代谢
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Guansong Hu,Junjian Chen,Yan Fan,Haiyan Zhou,Kunzhong Guo,Zhou Fang,Liangxu Xie,Lin Wang,Yingjun Wang
As an effective strategy to develop novel implants with a biomolecule, the efficiency of a copper-catalysed azide-alkyne cycloaddition (CuAAC) urgently requires improvement. Herein, we constructed a facile CuAAC system with catalytic CuSO 4 /sodium borohydride (CuAAC-Bor). As Cu nanoclusters (CuNCs) formed in situ , they showed stronger efficiency in immobilizing 41 types of peptides on Ti implants than traditional CuAAC with CuSO 4 /sodium ascorbate. Then, we mechanically revealed the significance of peptide size on CuAAC efficiency by all-atom molecular dynamics simulation and machine learning, and found that larger peptides preferred to adhere to Ti and CuNCs to increase their reaction opportunity. With CuAAC-Bor, HHC36-engineered implants strongly inhibited 5 types of clinical bacteria in vitro and prevented infection in vivo , and RGD-, DGEA-, QK- or YGFGG-engineered implants had high biocompatibilities with HUVECs / hBMSCs in vitro . Moreover, we demonstrated that QK-engineered implants prepared with CuAAC-Bor promoted the osteogenic differentiation of hBMSCs via the PI3K/Akt signalling pathway and triggered angiogenesis and osteogenesis in vivo . Our study shows that this facile and highly efficient CuAAC-Bor system holds high promise for the preparation of novel biomaterial surfaces.
研究领域:
生物材料
·
生物医学工程
·
分子生物学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Wenxiong Cao,Wei Wei,Bo Qiu,Yuan Liu,Shuang Xie,Qibo Fang,Xiaohong Li
Thrombosis seriously endangers human health with high incidence and mortality worldwide, and the clinical treatment is challenged by low bioavailability of thrombolytic agents, high bleeding risk and thrombosis relapse. Herein, ultrasound-powered Janus micromotors with stimuli-responsive multiple release capabilities are developed for efficient thrombolysis and inhibition of thrombosis recurrence. Resveratrol-loaded hyaluronic acid (HA Res ) nanoparticles (NPs) and urokinase plasminogen activator (uPA) were entrapped into H 2 O 2 -sensitive poly(1,4-cyclohexanedimethanol-co-oxalate) (POX) microparticles (MPs), followed by polydopamine capping and RGD grafting to obtain Janus rJPox@u-HA Res MPs. After RGD-mediated delivery to the thrombus site, the peroxalate ester bonds of POX are oxidized by the elevated H 2 O 2 to produce CO 2 , and the MP collapse accelerates the local release of uPA and HA Res NPs. The resulting CO 2 bubbles amplify the cavitation effect of ultrasound to promote thrombus penetration and site-specific uPA thrombolysis. The endothelial cell targeting and sustained resveratrol release from HA Res NPs dramatically improve endothelial cell viability, nitric oxide production and migration. Compared with free drug administration, the uPA loading into MPs significantly extends the half-life (15 folds) and bioavailability (7 folds), while the resveratrol inoculation into NPs increases the bioavailability 29 times. On an acute lower limb thrombosis model, the thrombus accumulation of MPs is promoted by RGD-mediated interactions with the activated platelets and ultrasound-driven penetration into thrombi, leading to almost full removal of blood clots. The H 2 O 2 -scavenging capability of POX, sustained resveratrol release and efficient thrombolysis alleviate oxidative stresses, eliminate coagulation biomarkers and repair the damaged endothelial layer to effectively inhibit thrombosis relapse. It is demonstrated that rJPox@u-HA Res /US treatment could not only achieve safe and site-specific thrombolytic therapy at the early stage but also restore vascular homeostasis to effectively prevent thrombosis recurrence.
研究领域:
生物医学工程
·
药学
·
治疗诊断学
·
纳米技术
·
药物递送系统
·
心血管疾病
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Zuyuan Luo,Siqi Zhang,Jijia Pan,Rui Shi,Hao Liu,Yalin Lyu,Xiao Han,Yan Li,Yue Yang,Zhixiu Xu,Yi Sui,En Luo,Yuanyuan Zhang,Shicheng Wei
The efficacy of stem cell-based bone tissue engineering has been hampered by cell death and limited fate control. A smart cell culture system with the capability of sequentially delivering multiple factors in specific growth stages, like the mechanism of the natural extracellular matrix modulating tissue formation, is attractive for enhancing cell activity and controlling cell fate. Here, a bone forming peptide-1 (BFP-1)-laden mesoporous silica nanoparticles ( [email protected] ) incorporated adhesion peptide, containing the arginine-glycine-aspartic acid (RGD) domain, modified alginate hydrogel (RA) system ( [email protected] ) was developed to promote the activity and stimulate osteo-differentiation of human mesenchymal stem cells (hMSCs) in sequence. The survivability and proliferation of hMSCs were enhanced in the adhesion peptide modified hydrogel. Next, BFP-1 released from [email protected] induced hMSCs osteo-differentiation after the proliferation stage. Moreover, BFP-1 near the cells was self-captured by the additional cell-peptide cross-linked networks formed by the ligands (RGD) binding to receptors on the cell surface, leading to long-term sustained osteo-stimulation of hMSCs. The results suggest that independent and sequential stimulation in proliferation and osteo-differentiation stages could synergistically enhance the survivability, expansion, and osteogenesis of hMSCs, as compared to stimulating alone or simultaneously. Overall, this study provided a new and valid strategy for stem cell expansion and osteo-differentiation in 2D or 3D culture systems, possessing potential applications in 3D bio-printing and tissue regeneration .
研究领域:
组织工程
·
干细胞生物学
·
生物医用材料
·
再生医学
✓ 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）