Endogenous stimuli-responsive linkers in nanoliposomal systems for cancer drug targeting

Maleki, Mahdi Faal; Jafari, Arash; Mirhadi, Elaheh; Askarizadeh, Anis; Golichenari, Behrouz; Hadizadeh, Farzin; Moghimi, Seyed Mohammad Jalilzadeh; Aryan, Reihaneh; Mashreghi, Mohammad; Jaafari, Mahmoud Reza

doi:10.1016/j.ijpharm.2019.118716

Cited by 30 publications

(8 citation statements)

References 207 publications

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“…Considering ethical aspects, mice were removed in case tumor growth was > 1000 mm 3 , or > 20% weight loss or sign of weakness was observed.…”

Section: In Vivo Antitumor Activitymentioning

confidence: 99%

“…Lack of the ability to penetrate in the dense extra cellular matrix (ECM) of tumor, return of the released drug to circulation and heterogeneity of tumors are the reasons responsible for this failure [2]. Different strategies have been used to improve tumor accumulation of NDDSs using endogenous and exogenous stimuli [3]. These NDDSs could response to the exogenous stimuli such as light and have the capacity to use in tumor imaging [4].…”

Section: Introductionmentioning

confidence: 99%

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Anti-Epcam Aptamer (Syl3c)-Functionalized Liposome for Targeted Delivery Of Doxorubicin: In Vitro And In Vivo Antitumor Studies in Mice Bearing C26 Colon Carcinoma

et al. 2020

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In this study, we have surface-functionalized PEGylated-nanoliposomal doxorubicin (DOX) with anti-EpCAM (epithelial cell adhesion molecule) aptamer via post-insertion of anti-EpCAM aptamer-conjugated DSPE-mPEG 2000 into Caelyx® (ED-lip). The size, charge, release profile, and cytotoxicity and cellular uptake of formulation were determined. The characterization of the ED-lip demonstrated the slightly increase in size and PDI along with the decrease in zeta potential which indicated that post-insertion efficiently done. The results of flow cytometry and fluorescent microscopy have shown that ED-lip enhanced the rate of cell uptake on C26 cell line compared to Caelyx®. The ED-lip also had more cytotoxic effects than Caelyx® which indicated the efficacy of anti-EpCAM aptamer as targeting ligand. The pharmacokinetic and tissue biodistribution of formulations in mice bearing C26 tumors demonstrated that ED-lip did not affect the distribution profile of DOX compared to Caelyx® in animal model. In addition, ED-lip effectively improved the tumor accumulation of DOX and promoted survival of animals compared to Caelyx®. These results suggest that the functionalization of Caelyx® with anti-EpCAM aptamer is promising in cancer treatment and merits further investigation.

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“…Considering ethical aspects, mice were removed in case tumor growth was > 1000 mm 3 , or > 20% weight loss or sign of weakness was observed.…”

Section: In Vivo Antitumor Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti-Epcam Aptamer (Syl3c)-Functionalized Liposome for Targeted Delivery Of Doxorubicin: In Vitro And In Vivo Antitumor Studies in Mice Bearing C26 Colon Carcinoma

et al. 2020

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“…, aminopeptidase), etc. have been investigated to construct enzyme-responsive DDS for tumor-tropism drug delivery 24 . The enzyme-responsive DDS could act in the following ways: (i) Enzyme-triggered drug release either by constructing nanocarriers with a structural scaffold susceptible to specific enzymes or by using an enzyme-sensitive linker between the nanocarrier and therapeutics.…”

Section: Strategies and Mechanisms Of Smart Drug Loading And Releasementioning

confidence: 99%

Smart drug delivery systems for precise cancer therapy

Wang

et al. 2022

Acta Pharmaceutica Sinica B

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“…The hypoxic areas are the main initiators of the successive above-mentioned stages and the formation of new blood vessels [14]. In this regard, azo-based molecules have the ability to target hypoxic regions and have been used in azoderivative chemotherapeutics as theragnostic agents in cancer [15,16]. It was revealed that azobenzene derivatives have reduction potentials in the range of that of hypoxic environments, which leads to reduction and consequently cleaving of N=N bonds [17].…”

Section: Introductionmentioning

confidence: 99%

Preparation and Characterization of Hypoxia Sensitive Cationic Liposomal Doxorubicin and Evaluation Its Anti-tumor Activity in Mice Bearing C26 Tumors

Mashreghi

Maleki

Askarizadeh

et al. 2021

Preprint

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The goal of this study was to prepare cationic nanoliposomal doxorubicin in which PEG molecule attached to the liposome via a hypoxia-sensitive azo linker. The cost-effective hypoxia-sensitive molecule (HSM) was synthesized composing of C18H37 lipophilic tail, azo-linker, and PEG2000 hydrophilic molecule. The NMR and FTIR were employed to characterize the HSM. Then, this compound was post-inserted into the cationic liposome (Cat-lip), and PEG-Azo-Cat-lip was prepared and characterized using DLS. In vitro release and cytotoxicity studies were performed in normoxic and hypoxic conditions. In vivo biodistribution and anti-tumor activities of the formulations were studied on mice bearing C-26 colon carcinoma tumor model and compared with PEGylated liposomal doxorubicin (Caelyx®). Besides, the histological test confirmed the formulation biosafety on healthy mice. The results of NMR and FTIR indicated the synthesis of HSM. The decrease in the zeta-potential of formulation from +18.4 mV for Cat-lip to +6.1 mV along with the increase in the size of the PEG-Azo-Cat-lip indicated the successful post-insertion of HSM. The release study showed that PEGylation results in the more stable PEG-Azo-Cat-lip compared to the Cat-lip. The increased cytotoxicity of the PEG-Azo-Cat-lip in the hypoxic condition also indicated the cleavage of the azo-linker in the hypoxic environment. In vivo biodistribution using animal imaging has shown higher tumor accumulation of the PEG-Azo-Cat-lip than Cat-lip during the 120 h of the study. The results of anti-tumor activities and biosafety of the formulations also showed the higher efficiency of the PEG-Azo-Cat-lip compared with the Cat-lip. The results of this study, indicated the anti-tumor efficacy of this hypoxia-sensitive which merits further investigation.

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Endogenous stimuli-responsive linkers in nanoliposomal systems for cancer drug targeting

Cited by 30 publications

References 207 publications

Anti-Epcam Aptamer (Syl3c)-Functionalized Liposome for Targeted Delivery Of Doxorubicin: In Vitro And In Vivo Antitumor Studies in Mice Bearing C26 Colon Carcinoma

Anti-Epcam Aptamer (Syl3c)-Functionalized Liposome for Targeted Delivery Of Doxorubicin: In Vitro And In Vivo Antitumor Studies in Mice Bearing C26 Colon Carcinoma

Smart drug delivery systems for precise cancer therapy

Preparation and Characterization of Hypoxia Sensitive Cationic Liposomal Doxorubicin and Evaluation Its Anti-tumor Activity in Mice Bearing C26 Tumors

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