Sequential Intra‐Intercellular Nanoparticle Delivery System for Deep Tumor Penetration

Ju, Caoyun; Mo, Ran; Xue, Jingwei; Zhang, Lei; Zhao, Zekai; Xue, Lingjing; Ping, Qineng; Zhang, Can

doi:10.1002/anie.201311227

Cited by 221 publications

(160 citation statements)

References 39 publications

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“…It could be predicted that the more nanoparticles penetrated into tumor cells and the higher possibility that nanoparticles penetrated deeply into tumors, the better anti-tumor efficacy could be obtained. Since the cancer stem cells could regenerate the tumor after therapy and existed in the deep region of tumors 36 , the nanoparticles penetrated into the deep region of tumors might also cause the necrosis of cancer stem cells and prevent the regeneration of tumors.…”

Section: Disscussionsmentioning

confidence: 99%

High Tumor Penetration of Paclitaxel Loaded pH Sensitive Cleavable Liposomes by Depletion of Tumor Collagen I in Breast Cancer

Zhang

Wang

Yang

et al. 2015

ACS Appl. Mater. Interfaces

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The network of collagen I in tumors could prevent the penetration of drugs loaded in nanoparticles, and this would lead to impaired antitumor efficacy. In this study, free losartan (an angiotensin inhibitor) was injected before treatment to reduce the level of collagen I, which could facilitate the penetration of nanoparticles. Then the pH-sensitive cleavable liposomes (Cl-Lip) were injected subsequently to exert the antitumor effect. The Cl-Lip was constituted by PEG(5K)-Hydrazone-PE and DSPE-PEG(2K)-R8. When the Cl-Lip reached to the tumor site by the enhanced permeability and retention (EPR) effect, PEG(5K)-Hydrazone-PE was hydrolyzed from the Cl-Lip under the low extra-cellular pH conditions of tumors, then the R8 peptide was exposed, and finally liposomes could be internalized into tumor cells by the mediation of R8 peptide. In vitro experiments showed both the cellular uptake of Cl-Lip by 4T1 cells and cytotoxicity of paclitaxel loaded Cl-Lip (PTX-Cl-Lip) were pH sensitive. In vivo experiments showed the Cl-Lip had a good tumor targeting ability. After depletion of collagen I, Cl-Lip could penetrate into the deep place of tumors, the tumor accumulation of Cl-Lip was further increased by 22.0%, and the oxygen distributed in tumor tissues was also enhanced. The antitumor study indicated free losartan in combination with PTX-Cl-Lip (59.8%) was more effective than injection with PTX-Cl-Lip only (37.8%) in 4T1 tumor bearing mice. All results suggested that depletion of collagen I by losartan dramatically increased the penetration of PTX-Cl-Lip and combination of free losartan and PTX-CL-Lip could lead to better antitumor efficacy of chemical drugs. Thus, the combination strategy might be a promising tactic for better treatment of solid tumors with a high level of collagen I.

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Section: Disscussionsmentioning

confidence: 99%

High Tumor Penetration of Paclitaxel Loaded pH Sensitive Cleavable Liposomes by Depletion of Tumor Collagen I in Breast Cancer

Zhang

Wang

Yang

et al. 2015

ACS Appl. Mater. Interfaces

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“…Furthermore, lipophilic SA on the surface (so-called minor core) [10] and the positive charge enabled the micelle strongly interact with cell membrane, which could drag micelles to the membrane of more inner cells. In consideration that CSCs were usually harbored in the center of a tumor [16], taking the DDS as a strategy would be accessible for drugs to reach them. For direct observation of the internal drug distribution, 3D cross-sectional images (Figure 3D) and videos (Supplementary materials) were showed.…”

Section: Resultsmentioning

confidence: 99%

Multi-cycle chemotherapy with the glycolipid-like polymeric micelles evade cancer stem cell enrichment in breast cancer therapy

Meng

Wen

et al. 2016

Oncotarget

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Multi-cycle chemotherapy is commonly used in the clinic, while the phenomena of enrichment of cancer stem cells (CSCs) and enhanced multi-drug resistance (MDR) are commonly involved. This research was designed for evaluating this successive administration. Chitosan oligosaccharide-g-stearic acid (CSOSA) polymer was used as the drug delivery system (DDS) to perform tri-cycle chemotherapy on a new tumor model induced by mammosphere cells. In vitro, on CSCs enriched mammospheres model, the doxorubicin-loaded CSOSA (CSOSA/DOX) displayed an improved growth inhibition effect measured by acid phosphatase assay (APH). While in vivo, the CSOSA/DOX micelles blocked tumor progression and led to a marked decrease of CSCs proportion as well as MDR capacity. What's more, the CSOSA/DOX helped decay the microenvironment and attenuate systemic side effects. We concluded that the CSOSA polymer could be a potential DDS for long-term multi-cycle chemotherapy in antitumor research.

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“…In recent years, a sufficient number of studies have been accumulated to substantiate the prospects for the use of nano-materials in microelectronics [1], energy physics [2], chemical [3], food [4], pharmaceutical [5], medical industry [6][7][8]. Nanoparticles (NPs) of metals are also of great practical importance in agriculture (in particular, in plant growing and for increasing soil fertility), where they can be used as nano-herbicides [9], nano-pesticides [10], as plant growth stimulants [11] and nano-fertilizers [12].…”

Section: Introductionmentioning

confidence: 99%

EFFECT OF Al2O3 NANOPARTICLES ON SOIL MICROBIOCENOSIS, ANTIOXIDANT STATUS AND INTESTINAL MICROFLORA OF RED CALIFORNIAN WORM (Eisenia foetida)

Yausheva¹,

Sizova²,

Gavrish³

et al. 2017

S-h. biol.

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A b s t r a c tWith the accumulation of experimental data it is evident that nanomaterials, which are widely used in human activity, look promising for agronomy. However, available publications on a comprehensive assessment of biological risks arising from nanoherbicides, nanofertilizers, etc., in particular on how the metal nanoparticles affect geobionts, are very limited. In the model experiments with California red worms Eisenia foetida as test organisms we studied the influence of aluminum oxide nanoparticles on soil biocoenosis and their biodegradation. We found an increase in mortality of worms up to 20 % at the maximum dosage of aluminum oxide nanoparticles introduced into the soil. Assay of antioxidant defense enzyme activity in the E. foetida revealed an increased superoxide dismutase and catalase level as influenced by the studied nanoparticles. The positive effect of their vermicomposting was shown. At increasing content of aluminum oxide nanoparticles (the nanoparticle dosage of 50, 100, 300, and 3000 mg/kg in the groups 1, 2, 3, and 4, respectively), the 61.7-67.6 % reduction in soil microorganism counts was found without vermicomposting vs. 55.6-61.3 % under vermicomposting. The number of microorganisms in the soil decreased in the groups 1, 2, 3 and 4 by 42.8, 52.4, 61.9 and 76.2 % for fungi, by 64.3, 77.9, 78.6 and 85.7 % for nitrogen-fixing bacteria, and by 22.7, 38.6, 84.1 and 86.4 % for bacteria cultured on starch-and-ammonia agar. The number of cellulolytic bacteria increased by 6.9 % in the group 1 and decreased by 16.7, 12.5 and 25.0 % in the groups 2, 3 and 4, respectively. A similar trend was observed under the influence of aluminum oxide nanoparticles on the E. foetida intestinal microflora. As the soil content of aluminum oxide nanoparticles increased from 50 to 3000 g/kg, the total number of microorganisms in the E. foetida intestine decreased by 9.7 to 43.2 %. In this, fungi decreased in the groups 1, 2, 3 and 4 by 18.0, 20.0, 39.0 and 40.0 % as compared to control. The number of nitrogen-fixing bacteria was insignificant in the control samples and decreased in the E. foetida intestine in the groups 1, 2, 3 and 4 by 16.0, 60.0, 78.8 and 80.0 %. The cellulolytic bacteria counts increased in the intestine of E. foetida (by 16.0 %) at minimum nanoparticle dosages, whereas in the groups 2, 3 and 4 this index was lower by 8.0, 32.0, 25.0 and 40.0 %. The number of bacteria cultured on starch-and-ammonia agar decreased in the E. foetida intestine in groups 1, 2, 3 and 4 by 13.3, 46.7, 60.0 and 73.3 %. Therefore, our data indicate dose-dependent effects of aluminum oxide nanoparticles and gradual development of their toxicity toward soil and intestinal microflora at increasing levels in the soil. The negative impact of the aluminum oxide nanoparticles on soil biocenosis was shown that was manifested in its depletion, leading to soil degradation and decreased fertility. We confirmed the necessity for complex assessment of nanoparticle biotoxicity in a variety of habitats. The antioxidant syst...

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Sequential Intra‐Intercellular Nanoparticle Delivery System for Deep Tumor Penetration

Cited by 221 publications

References 39 publications

High Tumor Penetration of Paclitaxel Loaded pH Sensitive Cleavable Liposomes by Depletion of Tumor Collagen I in Breast Cancer

High Tumor Penetration of Paclitaxel Loaded pH Sensitive Cleavable Liposomes by Depletion of Tumor Collagen I in Breast Cancer

Multi-cycle chemotherapy with the glycolipid-like polymeric micelles evade cancer stem cell enrichment in breast cancer therapy

EFFECT OF Al2O3 NANOPARTICLES ON SOIL MICROBIOCENOSIS, ANTIOXIDANT STATUS AND INTESTINAL MICROFLORA OF RED CALIFORNIAN WORM (Eisenia foetida)

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