Tumor-targeted nano-delivery system of therapeutic RNA

Wang, Maonan; Zhao, J.; Jiang, Hui; Wang, Xuemei

doi:10.1039/d1mh01969d

Cited by 29 publications

(17 citation statements)

References 236 publications

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“…It is common knowledge that the EPR effect can increase the accumulation of local drug concentration. Compared with active targeting ( Wang et al, 2022b ), the delivery efficiency of EPR is lower, which is not enough to make the drug completely distributed in the tumor tissue. Moreover, due to the specificity of the tumor microenvironment, the tumor has a certain resistance to temperature changes and ROS, leading to the failure to eliminate all tumor cells.…”

Section: Resultsmentioning

confidence: 99%

Fe/MOF based platform for NIR laser induced efficient PDT/PTT of cancer

Liang

Chen

et al. 2023

Front. Bioeng. Biotechnol.

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Introduction: Photodynamic therapy (PDT) and photothermal therapy (PTT) are widely used in the treatment of tumors. However, their application in the treatment of clinical tumors is limited by the complexity and irreversible hypoxia environment generated by tumor tissues. To overcome this limitation, a nanoparticle composed of indocyanine green (ICG) and Fe-MOF-5 was developed.Methods: We prepared F-I@FM5 and measured its morphology, particle size, and stability. Its enzyme like ability and optical effect was verified. Then we used MTT, staining and flow cytometry to evaluated the anti-tumor effect on EMT-6 cells in vitro. Finally, the anti-tumor effect in vivo has been studied on EMT-6 tumor bearing mice.Results: For the composite nanoparticle, we confirmed that Fe-MOF-5 has the best nanozyme activity. In addition, it has excellent photothermal conversion efficiency and generates reactive oxygen species (ROS) under near-infrared light irradiation (808 nm). The composite nanoparticle showed good tumor inhibition effect in vitro and in vivo, which was superior to the free ICG or Fe-MOF-5 alone. Besides, there was no obvious cytotoxicity in major organs within the effective therapeutic concentration.Discussion: Fe-MOF-5 has the function of simulating catalase, which can promote the decomposition of excessive H2O2 in the tumor microenvironment and produce oxygen to improve the hypoxic environment. The improvement of tumor hypoxia can enhance the efficacy of PDT and PTT. This research not only provides an efficient and stable anti-tumor nano platform, but also has broad application prospects in the field of tumor therapy, and provides a new idea for the application of MOF as an important carrier material in the field of photodynamic therapy.

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Section: Resultsmentioning

confidence: 99%

Fe/MOF based platform for NIR laser induced efficient PDT/PTT of cancer

Liang

Chen

et al. 2023

Front. Bioeng. Biotechnol.

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“…As shown in Figure 5c, the cellular uptake of Bio‐PEG‐CN/DNA complexes was significantly decreased at low temperature compared to 37°C, suggesting that the internalization of these complexes was at least partially realized by energy‐dependent endocytosis 53 . It should be noted that endocytosis is considered to be the main route for non‐viral nanocarriers to enter cells, and it proceeds via different mechanisms: caveolae‐mediated endocytosis (CavME), clathrin‐mediated endocytosis (CME), and “lipid rafts”‐like endocytosis and micropinocytosis 54 . Herein, genistein (GE, CavME inhibitor), 55 amiloride hydrochloride (AM, macropinocytosis inhibitor), 53 methyl‐β‐cyclodextrin (MβCD, “lipid rafts”‐like endocytosis inhibitor), 56 and chlorpromazine (CPZ, CME inhibitor) 53 were utilized to identify the main mechanism of cellular uptake for this system.…”

Section: Resultsmentioning

confidence: 99%

“…53 It should be noted that endocytosis is considered to be the main route for non-viral nanocarriers to enter cells, and it proceeds via different mechanisms: caveolae-mediated endocytosis (CavME), clathrin-mediated endocytosis (CME), and "lipid rafts"-like endocytosis and micropinocytosis. 54 Herein, genistein (GE, CavME inhibitor), 55 amiloride hydrochloride (AM, macropinocytosis inhibitor), 53 methyl-β-cyclodextrin (MβCD, "lipid rafts"-like endocytosis inhibitor), 56 and chlorpromazine (CPZ, CME inhibitor) 53 were utilized to identify the main mechanism of cellular uptake for this system. As shown in Figure 5d, after the Bio-PEG-CN/DNA complexes were pre-incubated with GE or AM at 37 C, the fluorescence signal in the cells decreased significantly.…”

Section: Internalization Of Dna Complexesmentioning

confidence: 99%

Light controlled self‐escape capability of non‐cationic carbon nitride‐based nanosheets in lysosomes for hepatocellular carcinoma targeting stimulus‐responsive gene delivery

Liu

Jiang

et al. 2023

Bioengineering & Transla Med

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High positive charge‐induced toxicity, easy lysosomal degradation of nucleic acid drugs, and poor lesion sites targeting are major problems faced in the development of gene carriers. Herein, we proposed the concept of self‐escape non‐cationic gene carriers for targeted delivery and treatment of photocontrolled hepatocellular carcinoma (HCC) with sufficient lysosome escape and multiple response capacities. Functional DNA was bound to the surface of biotin‐PEG2000‐modified graphitic carbon nitride (Bio‐PEG‐CN) nanosheets to form non‐cationic nanocomplexes Bio‐PEG‐CN/DNA. These nanocomposites could actively target HCC tissue. Once these nanocomplexes were taken up by tumor cells, the accumulated reactive oxygen species (ROS) generated by Bio‐PEG‐CN under LED irradiation would disrupt the lysosome structure, thereby facilitating nanocomposites escape. Due to the acidic microenvironment and lipase in the HCC tissue, the reversible release of DNA could be promoted to complete the transfection process. Meanwhile, the fluorescence signal of Bio‐PEG‐CN could be monitored in real time by fluorescence imaging technology to investigate the transfection process and mechanism. In vitro and in vivo results further demonstrated that these nanocomplexes could remarkably upregulate the expression of tumor suppressor protein P53, increased tumor sensitivity to ROS generated by nanocarriers, and realized effective gene therapy for HCC via loading P53 gene.

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“…3 The mechanism of endocytosis could be respectively divided into: macropinocytosis, clathrin-mediated endocytosis (CME), caveolae-mediated endocytosis (CavME) and ‘‘lipid rafts’’-like endocytosis. 50 Subsequently, amiloride hydrochloride (AM, macropinocytosis inhibitor), 51 chlorpromazine (CPZ, CME inhibitor), 51 genistein (GE, caveolae-mediated endocytosis inhibitor), 52 and methyl-β-cyclodextrin (MβCD, ‘‘lipid rafts’’-like endocytosis inhibitor) 53 were used to determine the mechanism of cell internalization. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%