DRUG DELIVERY
·
2022
·
IF 6.819
Ziyue Wang,Cuicui Wu,Jinren Liu,Shunxin Hu,Junli Yu,Qiangqiamg Yin,Hongda Tian,Zhipeng Ding,Guiqiang Qi,Li Wang,Liguo Hao
Sorafenib (SRF) presents undesirable effects in clinical treatment, due to the lack of targeting, poor water solubility, and obvious side effects. In this study, we constructed a novel nanodrug carrier system for accurate and efficient delivery of SRF, improving its therapeutic effects and achieving tumor-specific imaging. The hollow mesoporous MnO2 (H-MnO2) nanoparticles equipped with target substance aptamers (APT) on the surface were used to load SRF for the first time. The resulting H-MnO2-SRF-APT could specifically bound to glypican-3 (GPC3) receptors on the surface of hepatocellular carcinoma (HCC), rapidly undergoing subsequent degradation under decreased pH conditions in the tumor microenvironment (TME) and releasing the loaded SRF. In this process, Mn2+ ions were used for T1-weighted magnetic resonance imaging simultaneously. The in vitro cell experiments indicated that H-MnO2-SRF-APT showed much more effects on the inhibition in the proliferation of Huh7 and HepG2 HCC cells than that of the non-targeted H-MnO2-SRF and free SRF. Besides, the in vivo results further confirmed that H-MnO2-SRF-APT could effectively inhibit the growth of xenograft tumors Huh7 in the naked mouse with good biosafety. In conclusion, H-MnO2-SRF-APT could significantly enhance the therapeutic effect of SRF and is expected to be a new way of diagnosis and treatment of HCC.
研究领域:
纳米技术
·
药学
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Ziying Zhang,Weishen Zeng,Ning Guo,Mengnan Ran,Huixuan Gan,Quanxin Wu,Jiehua Xu,Hao Wang,Shisong Han,Yun Liu
As an emerging therapeutic method, the application of sonodynamic therapy (SDT) is hindered by its intrinsic unsatisfactory efficiency, the tumor hypoxia and low tumor specificity. Here, we reported the design of a tumor-targeting multifunctional nanodrug for O 2 -generation/O 2 -economization dually enhanced SDT/chemodynamic therapy (CDT) combination therapy. After the co-encapsulation of sonosensitizer indocyanine green (ICG) and oxidative phosphorylation inhibitor metformin (Met) into hollow MnO 2 (H-MnO 2 ) nanoparticles, ICG/Met@H-MnO 2 @MPN-FA (IMMMF) was conveniently prepared through the formation of metal–phenolic networks (MPNs) between Fe 3+ and folic acid (FA) immobilized tannic acid (TA, TA-FA) onto its surface. In vitro experiments indicated its selective uptake by 4T1 cells via the specific folate receptors-FA interactions. Responding to glutathione (GSH) and the acidic environment, the decomposition of IMMMF led to the release of Mn 2+ and Fe 2+ for enhanced CDT, and ICG for SDT. Furthermore, Met was continuously released to reduce O 2 consumption for enhanced SDT. More importantly, IMMMF catalyzed the endogenous H 2 O 2 into O 2 for further enhanced SDT. Expectedly, both in vitro and in vivo antitumor assays confirmed its satisfactory therapeutic efficiency via CDT/SDT synergistic therapy. Hence, this intelligent sonocatalytic nanoagent emerges as a promising candidate for CDT-enhanced SDT, which also provides a novel strategy for dually alleviating tumor hypoxia with better therapy.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xingbo Wang,Xiaoqing Han,Jiao Yan,Yanjing Wang,Panpan Song,Yaqing Kang,Xueyan Zhang,Xiaoman Shi,Guan Xue,Abdur Rauf,Daguang Zhang,Haiyuan Zhang
Reprogramming of tumor associated macrophages (TAMs) from M2 to M1 phenotype is becoming a feasible strategy for tumor immunotherapy, however, its efficacy is potentially constrained by the acellular components of immunosuppressive tumor microenvironment (TME). Herein, hollow MnO 2 (HMnO 2 ) nanoparticles were loaded with autophagy inhibitor chloroquine (CQ), carried both lactate oxidase (LOX) and glucose oxidase (GOX) on their surface, and further were camouflaged with tumor cell membrane, forming the final mCMLG nanoparticles for TME immunostimulation. After intravenous injection, mCMLG nanoparticles effectively accumulated in the tumor area and were taken up by tumor cells. Under the acidic conditions, MnO 2 reacted with endogenous hydrogen peroxide (H 2 O 2 ) to generate O 2 and Mn 2+ , resulting in the exposure of LOX and GOX as well as the release of CQ. The exposed enzymes reduced the level of lactate (a predominant acellular component), alleviating the inhibition on TAM reprogramming; hydroxyl radical (·OH) generated by Fenton-like reaction of Mn 2+ could directly promote this reprogramming, thus effectively facilitating the reprogramming of TME from immunosuppressive to immunostimulatory. Moreover, ·OH also induced chemodynamic therapy (CDT) effect against tumor cells, which was further amplified by CQ. This study corroborates that mCMLG nanoparticles can effectively inhibit tumor growth through the enhanced immunotherapy and CDT.
研究领域:
纳米技术
·
癌症免疫治疗
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
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