Effects of tumor microenvironments on targeted delivery of glycol chitosan nanoparticles

Yhee, Ji Young; Jeon, Sangmin; Yoon, Hong Yeol; Shim, Man Kyu; Ko, Hyewon; Min, Jiwoong; Na, Jin Hee; Chang, Hyeyoun; Han, Hyounkoo; Kim, Jong Ho; Suh, Minah; Lee, Hyukjin; Park, Jae Hyung; Kim, Kwangmeyung; Kwon, Ick Chan

doi:10.1016/j.jconrel.2017.09.015

Cited by 67 publications

(32 citation statements)

References 39 publications

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“…To prepare glycol chitosan nanoparticles (CNPs), hydrophobic 5β-cholanic acid was chemically conjugated to the hydrophilic glycol chitosan through amide linkage formation in the presence of EDC and NHS [ 15 , 38 ]. Briefly, 150 mg of 5β-cholanic acid was dissolved in 120 mL of methanol and mixed with EDC (120 mg) and NHS (72 mg).…”

Section: Methodsmentioning

confidence: 99%

“…However, challenges remain to further improve the therapeutic efficacy of drug-loaded nanoparticles in heterogeneous tumors [ 10 , 11 , 12 ]. In particular, the delivery efficacy of drug-loaded nanoparticles is hampered greatly by limited deep tumor penetration in the complex tumor microenvironment [ 13 , 14 , 15 ]. It has been known that heterogeneous tumors differ in their vascular structure and perfusion rate [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the thick extracellular matrix (ECM) which consists of collagen and hyaluronan (HA) in the tumor tissue can inhibit the deep tissue penetration of drug-loaded nanoparticles [ 18 , 19 ]. This is because the dense ECM can act as a physical barrier to the accumulation and deep tissue penetration of drug-loaded nanoparticles [ 15 , 20 ]. Thus, the development of a way to ensure a deep penetration of drug-loaded nanoparticles into tumor tissue is an essential challenge to improve the therapeutic efficacy of nanoparticle-based drug delivery systems in cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

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Deep Tumor Penetration of Doxorubicin-Loaded Glycol Chitosan Nanoparticles Using High-Intensity Focused Ultrasound

et al. 2020

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The dense extracellular matrix (ECM) in heterogeneous tumor tissues can prevent the deep tumor penetration of drug-loaded nanoparticles, resulting in a limited therapeutic efficacy in cancer treatment. Herein, we suggest that the deep tumor penetration of doxorubicin (DOX)-loaded glycol chitosan nanoparticles (CNPs) can be improved using high-intensity focused ultrasound (HIFU) technology. Firstly, we prepared amphiphilic glycol chitosan-5β-cholanic acid conjugates that can self-assemble to form stable nanoparticles with an average of 283.7 ± 5.3 nm. Next, the anticancer drug DOX was simply loaded into the CNPs via a dialysis method. DOX-loaded CNPs (DOX-CNPs) had stable nanoparticle structures with an average size of 265.9 ± 35.5 nm in aqueous condition. In cultured cells, HIFU-treated DOX-CNPs showed rapid drug release and enhanced cellular uptake in A549 cells, resulting in increased cytotoxicity, compared to untreated DOX-CNPs. In ECM-rich A549 tumor-bearing mice, the tumor-targeting efficacy of intravenously injected DOX-CNPs with HIFU treatment was 1.84 times higher than that of untreated DOX-CNPs. Furthermore, the deep tumor penetration of HIFU-treated DOX-CNPs was clearly observed at targeted tumor tissues, due to the destruction of the ECM structure via HIFU treatment. Finally, HIFU-treated DOX-CNPs greatly increased the therapeutic efficacy at ECM-rich A549 tumor-bearing mice, compared to free DOX and untreated DOX-CNPs. This deep penetration of drug-loaded nanoparticles via HIFU treatment is a promising strategy to treat heterogeneous tumors with dense ECM structures.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Deep Tumor Penetration of Doxorubicin-Loaded Glycol Chitosan Nanoparticles Using High-Intensity Focused Ultrasound

et al. 2020

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“…It has been reported that there is a significant different in pH between normal tissue (pH 7.4) and tumor microenvironment (pH 6.8-5.0). 36,37 Therefore, pH-responsive drug release could not only increase drug release but also decrease nonspecific toxicity. In this study, pH-independent drug release behavior was investigated at different pH values (pH 7.4 and 5.0).…”

Section: In Vitro Drug Release From the Preparationsmentioning

confidence: 99%

Mitochondria-targeted delivery of doxorubicin to enhance antitumor activity with HER-2 peptide-mediated multifunctional pH-sensitive DQAsomes

Shi

Zhang

et al. 2018

IJN

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IntroductionMultidrug resistance (MDR) of breast cancer is the major challenge to successful chemotherapy while mitochondria-targeting therapy was a promising strategy to overcome MDR.Materials and methodsIn this study, HER-2 peptide-PEG2000-Schiff base-cholesterol (HPSC) derivate was synthesized successfully and incorporated it on the surface of the doxorubicin (DOX)-loaded dequalinium (DQA) chloride vesicle (HPS-DQAsomes) to treat drug-resistant breast cancer. Evaluations were performed using human breast cancer cell and DOX-resistant breast cancer cell lines (MCF-7 and MCF-7/ADR).ResultsThe particle size of HPS-DQAsomes was ~110 nm with spherical shape. In vitro cytotoxicity assay indicated that HPS-DQAsomes could increase the cytotoxicity against MCF-7/ADR cell line. Cellular uptake and mitochondria-targeting assay demonstrated that HPS-DQAsomes could target delivering therapeutical agent to mitochondria and inducing mitochondria-driven apoptosis process. In vivo antitumor assay suggested that HPS-DQAsomes could reach favorable antitumor activity due to both tumor targetability and sub-organelles’ targetability. Histological assay also indicated that HPS-DQAsomes showed a strong apoptosis-inducing effect. No obvious systematic toxicity of HPS-DQAsomes could be observed.ConclusionIn summary, multifunctional HPS-DQAsomes provide a novel and versatile approach for overcoming MDR via mitochondrial pathway in cancer treatment.

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“…GC-NABP was constructed by covalently conjugating the hydrophobic, H 2 O 2 -responsive and two-photon uorophore, NABP, onto side chains of glycol chitosan (GC), which is a water-soluble, low-cost, biocompatible and biodegradable polymer with the capability of pH-titratable charge. [39][40][41][42][43][44] GC-NABP exhibited an amphiphilic feature and could self-assemble into nanosized micelles in aqueous solution. Notably, taking advantage of pHtitratable amino groups on GC (pK a $ 6.5), the surface charge of the nanoprobe could transition from negative at physiologic pH to positive in the acidic tumor microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Tumor-acidity activated surface charge conversion of two-photon fluorescent nanoprobe for enhanced cellular uptake and targeted imaging of intracellular hydrogen peroxide

Chen

et al. 2019

Chem. Sci.

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Effects of tumor microenvironments on targeted delivery of glycol chitosan nanoparticles

Cited by 67 publications

References 39 publications

Deep Tumor Penetration of Doxorubicin-Loaded Glycol Chitosan Nanoparticles Using High-Intensity Focused Ultrasound

Deep Tumor Penetration of Doxorubicin-Loaded Glycol Chitosan Nanoparticles Using High-Intensity Focused Ultrasound

Mitochondria-targeted delivery of doxorubicin to enhance antitumor activity with HER-2 peptide-mediated multifunctional pH-sensitive DQAsomes

Tumor-acidity activated surface charge conversion of two-photon fluorescent nanoprobe for enhanced cellular uptake and targeted imaging of intracellular hydrogen peroxide

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