N-trimethyl chitosan nanoparticle-encapsulated lactosyl-norcantharidin for liver cancer therapy with high targeting efficacy

Guan, Mingyu; Zhou, Yi; Zhu, Qiao-Ling; Liu, Yang; Bei, Yi; Xue-nong, Zhang; Zhang, Qiang

doi:10.1016/j.nano.2012.01.009

Cited by 75 publications

(40 citation statements)

References 35 publications

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“…TMC was synthesized in our laboratory with a quaternization degree of 65% 14 and an average MW of 6.5 kD. Dulbecco's Modified Eagle's Medium was provided by Hyclone (GE Healthcare Bio-Sciences Corp., Piscataway, NJ, USA).…”

Section: Methodsmentioning

confidence: 99%

Liposomes coated with N-trimethyl chitosan to improve the absorption of harmine in vivo and in vitro

Chen¹,

Yuan²,

Liu³

et al. 2016

IJN

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In this study, harmine liposomes (HM-lip) were prepared through the thin-film hydration–pH-gradient method and then coated with N -trimethyl chitosan (TMC). Particle size, zeta potential, entrapment efficiency, and in vitro release of HM-lip and TMC-coated harmine liposomes (TMC-HM-lip) were also determined. Sprague Dawley rats were further used to investigate the pharmacokinetics in vivo. Retention behavior in mouse gastrointestinal tract (GIT) was studied through high-performance liquid chromatography and near-infrared imaging. Degradation was further evaluated through incubation with Caco-2 cell homogenates, and a Caco-2 monolayer cell model was used to investigate the uptake and transport of drugs. HM-lip and TMC-HM-lip with particle size of 150–170 nm, an entrapment efficiency of about 81%, and a zeta potential of negative and positive, respectively, were prepared. The release of HM from HM-lip and TMC-HM-lip was slower than that from HM solution and was sensitive to pH. TMC-HM-lip exhibited higher oral bioavailability and had prolonged retention time in GIT. HM-lip and TMC-HM-lip could also protect HM against degradation in Caco-2 cell homogenates. The uptake amount of TMC-HM-lip was higher than that of HM and HM-lip. TMC-HM-lip further demonstrated higher apparent permeability coefficient ( P app ) from the apical to the basolateral side than HM and HM-lip because of its higher uptake and capability to open tight junctions in the cell monolayers. TMC-HM-lip can prolong the retention time in the GIT, protect HM against enzyme degradation, and improve transport across Caco-2 cell monolayers, thus enhancing the oral bioavailability of HM.

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Section: Methodsmentioning

confidence: 99%

Liposomes coated with N-trimethyl chitosan to improve the absorption of harmine in vivo and in vitro

Chen¹,

Yuan²,

Liu³

et al. 2016

IJN

Self Cite

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“…Available data indicate that the number of cancer-related deaths is more than those caused by AIDS, malaria, and tuberculosis combined; about one in four deaths is due to cancer. A major reason for this high mortality rate lies in resistant nature of variety of tumors against anti-cancer agents and bystander toxicity on healthy tissues and organs [1][2][3][4]. Cancer is caused by complex processes, which are directly linked to 'cell division', the fundamental process of life.…”

Section: Introductionmentioning

confidence: 99%

Macrophages directed approaches are paramount for effective cancer immunotherapies

Nadella¹,

Singh²,

Prakash³

2016

Integr Cancer Sci Therap

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Macrophages are double edge sword component of immunity and display phenotypical and functional plasticity which enable them to both promote and eliminate established tumors. Under the influence of immunosuppressive tumor microenvironment, tumor infiltrating iNOS+ and CD11b+ M-1 regulatory macrophages get polarized to Tumor associated macrophages (TAM) which are Ym-1 and Arginase+ iNOS-(M-2) and tropic to variety of tumors. Increased density of TAM in the variety of tumors has been correlated with poor prognosis which is due to their influence on angiogenesis and tissue re-modelling by which TAM support tumorigenesis as well metastasis. Apart from this, TAMs are also responsible for the maintenance of tumor microenvironment by their virtue of inducing endothelium anergy, which actually represent physical barrier for majority of cancer directed immune / chemotherapies. Therefore functional retuning of TAM to an M-1 phenotype is paramount for effective immunotherapy against established tumors which could be afforded by total body gamma irradiation in neoadjuvant settings or adoptive transfer of iNOS+ macrophages. In this review, we will discuss both existing as well future cancer directed immuno / adjuvant therapies targetting immunosuppresive tumor microenviorment particularly tumor-associated macrophages (TAM) for enhancing immunty against solid tumors (adenocarcinoma).

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“…Chitosan (CS), the only natural alkaline polysaccharose, has good biodegradability and biocompatibility as well as antibacterial property and immunoregulation activity. However, the application of CS has been hampered largely by its solubility only in acidic environments with pH values lower than 6.0 (Guan et al, 2012a). To overcome this problem, N-trimethyl chitosan, a partially quaternized chitosan derivative was synthetized and it was soluble in the entire pH range (Guan et al, 2012a).…”

Section: Introductionmentioning

confidence: 99%

“…However, the application of CS has been hampered largely by its solubility only in acidic environments with pH values lower than 6.0 (Guan et al, 2012a). To overcome this problem, N-trimethyl chitosan, a partially quaternized chitosan derivative was synthetized and it was soluble in the entire pH range (Guan et al, 2012a). In our study, the hydrophilic group (ÀCOOH) was imported into the CS molecule via the alcoholysis reaction between NCTD and CS.…”

Section: Introductionmentioning

confidence: 99%

Primaryin vitroandin vivoevaluation of norcantharidin-chitosan/poly (vinyl alcohol) for cancer treatment

Lü

et al. 2013

Drug Delivery

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Two novel polymer-drug conjugates norcantharidin-poly(vinyl alcohol) and norcantharidinchitosan (NCTD-PVA and NCTD-CS) were synthesized via alcoholysis reaction and characterized by 1 H-NMR and FTIR. NCTD was released from the conjugates via hydrolysis, faster in PBS (pH 5.0) than that in PBS (pH 7.4). NCTD-PVA and NCTD-CS inhibited human esophageal carcinoma ECA-109 cell and murine breast cancer EMT6 cell growth in a dose-dependent manner. The IC 50 values of NCTD, NCTD-PVA and NCTD-CS on ECA-109 cell at 48 h were 9.4 AE 0.9, 55.3 AE 3.0 and 168.8 AE 8.9 mg/ml, respectively, and the IC 50 values of the three compounds on EMT6 cell were 3.1 AE 0.3, 30.5 AE 5.4 and 90.7 AE 8.1 mg/ml, respectively. The two conjugates both induced esophageal carcinoma ECA-109 cell apoptosis and arrested cell cycle at the S phase. Caspase-8 and caspase-3 were activated in the ECA-109 cell after incubating with NCTD-PVA or NCTD-CS. The primary in vivo antitumor activity was assessed in the EMT6 tumor-bearing mouse model. NCTD-PVA and NCTD-CS displayed higher tumor inhibition rates than that of free NCTD.

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N-trimethyl chitosan nanoparticle-encapsulated lactosyl-norcantharidin for liver cancer therapy with high targeting efficacy

Cited by 75 publications

References 35 publications

Liposomes coated with N-trimethyl chitosan to improve the absorption of harmine in vivo and in vitro

Liposomes coated with N-trimethyl chitosan to improve the absorption of harmine in vivo and in vitro

Macrophages directed approaches are paramount for effective cancer immunotherapies

Primaryin vitroandin vivoevaluation of norcantharidin-chitosan/poly (vinyl alcohol) for cancer treatment

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