Liposomal CpG-ODN: An in vitro and in vivo study on macrophage subtypes responses, biodistribution and subsequent therapeutic efficacy in mice models of cancers

Nikoofal-Sahlabadi, Sara; Riahi, Maryam Matbou; Sadri, Kayvan; Badiee, Ali; Nikpoor, Amin Reza; Jaafari, Mahmoud Reza

doi:10.1016/j.ejps.2018.04.018

Cited by 43 publications

(26 citation statements)

References 42 publications

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“…The percent of tumor growth delay (%TGD) was obtained from following formula: %TGD = (the mean TTE of treatment group -the mean TTE of the control group)/the mean TTE of the control group ×100 60,61 . Furthermore, increased life span (%ILS) for each treatment group was calculated according to the following equation: %ILS = (mean survival time of treatment group/mean survival time of PBS group × 100)−100 62,63 .…”

Section: Ee(%)mentioning

confidence: 99%

Optimization of Docetaxel Loading Conditions in Liposomes: proposing potential products for metastatic breast carcinoma chemotherapy

Vakili‐Ghartavol

Rezayat

Faridi‐Majidi

et al. 2020

Sci Rep

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Docetaxel (DtX) was loaded in nanoliposomes based on a new remote loading method using mannitol and acetic acid as hydration buffer. DTX loading conditions were optimized, and the final formulations were prepared according to the best parameters which were HSPC/mPEG2000-DSPE/Chol (F1), HSPC/mPEG2000-DSPE/DPPG/Chol (F2), HSPC/mPEG2000-DSPE/DSPG/Chol (F3), at molar ratios of 85/5/10, 80/5/5/10, 80/5/5/10, respectively. DTX-liposomes were found of desired size (~115 nm) and homogeneity (pDi ≤ 0.2), high drug encapsulation efficacy (34-67%) and DTX concentration, and favorable stability. Passive loaded counterparts liposomes showed three times lower encapsulation efficacy compared to the remote loaded liposomes. The drug release of remote loaded liposomes in plasma 50% was significantly more controlled and less in comparison with their passive loaded counterparts (p < 0.0001). The IC50 values of formulations were determined on MCF-7, 4T1, TUBO, NIH/3T3 cell lines. The biodistribution of iodinated docetaxel as free or liposomal form exhibited significantly greater accumulation of DTX-liposomes in tumors than that of free docetaxel due to the EPR effect. In vivo experiment with BALB/c mice bearing 4T1 or TUBO breast carcinoma tumors also showed that DTX-liposomes could significantly delay tumor growth and prolonged the survival time in comparison with control and Taxotere groups at the similar dose of 8 mg/kg. F1 and F2 formulations were stable and showed good anti-tumor activity and merit further investigation. Taxanes have extremely low solubility in water and pharmaceutical concerns caused by their bulky polycyclic structure 1,2. Nanocarriers, including liposomes, micelles, and polymeric or inorganic nanoparticles have been developed to prepare a higher therapeutic efficacy, lower toxicity, and controlled delivery of chemotherapeutic agents 1,3-8. Among them, liposomes, composed of phospholipids, have been explored for their use in clinically approved formulations for more than five decades 6,9-15. Liposomes, compared with other nanocarriers, present specific advantages and promising capabilities in delivering a plethora of otherwise inefficient drugs by modifying their physicochemical characteristics and biodistribution, and by reducing the toxic effects of drugs 6,16,17. Moreover, chemical and biological stability under different storage conditions of agents and during blood circulation, and biocompatible characteristics recommend them as carriers for therapeutic agents 6,9,17,18. There are currently two liposomal formulations of docetaxel (DTX) in clinical development. LE-DT (NeoPharm, Inc.) and ATI-1123 (Azaya Therapeutics, Inc.) have undergone phase I studies and appears to be well tolerated (ClinicalTrials.gov in May 2019). In general, drug loading into the liposomes is attained by either passive or active (remote) methods 19. In passive loading method, dried thin film is hydrated in aqueous solutions containing the drug of interest. In contrast, remote loading technique is loading of a drug into performed lip...

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Section: Ee(%)mentioning

confidence: 99%

Optimization of Docetaxel Loading Conditions in Liposomes: proposing potential products for metastatic breast carcinoma chemotherapy

Vakili‐Ghartavol

Rezayat

Faridi‐Majidi

et al. 2020

Sci Rep

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“…As an alternative to conjugation, liposomal delivery of CpGODN has been demonstrated to offer important advantages including protection from DNase degradation, extension of retention time inside the body, improved cellular uptake, delivery to target tissues and slow release over a long period of time [17]. Various types of liposomal CpGODN have been developed to achieve immunostimulation, and encapsulation or co-administration of CpG motifs into/with liposomes have been shown to dramatically enhance the potency of immunogens compared to free CpGODN [18][19][20][21].…”

Section: Graphical Abstract 1 Introductionmentioning

confidence: 99%

Design of a novel vaccine nanotechnology-based delivery system comprising CpGODN-protein conjugate anchored to liposomes

Chatzikleanthous

Schmidt

Buffi

et al. 2020

Journal of Controlled Release

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Although the well-known Toll like receptor (TLR9) agonist CpGODN has shown promising results as vaccine adjuvant in preclinical and clinical studies, its in vivo stability and potential systemic toxicity remain a concern. In an effort to circumvent these issues, different strategies have been employed to increase its stability, localise action and reduce dosage. These include conjugation of CpGODN with proteins or encapsulation/adsorption of CpGODN into/onto liposomes and have resulted in enhanced immunopotency compared to co-administration of free CpGODN and antigen. Here, we designed a novel delivery system of CpGODN based on its conjugation to serve as anchor for liposomes. Thiolmaleimide chemistry was utilised to covalently ligate the Group B Streptococcus (GBS) GBS67 protein antigen with the CpGODN TLR9 agonist. This treatment did not alter protein's ability to be recognised by specific antibodies or the CpGODN to function as a TLR9 agonist. Due to its negative charge, the protein conjugate readily electrostatically bound cationic liposomes composed of 1, 2-distearoyl-snglycero-3-phosphocholine (DSPC), cholesterol and dimethyldioctadecylammonium bromide (DDA).The novel cationic liposomes-protein conjugate complex (GBS67-CpGODN+L) shared similar vesicle characteristics (size and charge) compared to free liposomes but exhibited different structure and morphology. Following intramuscular immunisation, GBS67-CpGODN+L formed a vaccine depot at the injection site and induced a remarkable increase of functional immune responses against GBS compared to the simple co-administration of GBS67, CpGODN and liposomes. This work demonstrates that the conjugation of CpGODN to GBS67 in conjunction with adsorption on cationic liposomes, can promote co-delivery leading to the induction of a multifaceted immune response at low antigen and CpGODN doses. Our findings highlight the potential for harnessing the immunostimulatory properties of different adjuvants to develop more effective nanostructure-based vaccine platforms.

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“…These problems are expected to resolve by encapsulating single-strand (ss) nucleic acid into a delivery carrier or making it self-assemble into a nanostructure that improves its stability in vivo as well as more efficient internalization ratio to innate immune cells. Currently, various carriers such as cationic polymer polyethylenimines (PEI) [6], liposomes [7, 8], and microparticles [9] were utilized to the delivery of CpG-ODN; there are still some drawbacks that remain to be improved, such as its cytotoxicity, limited loading rate and etc.…”

Section: Introductionmentioning

confidence: 99%

Potent anti-tumor immunostimulatory biocompatible nanohydrogel made from DNA

et al. 2019

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Unmethylated CpG oligodeoxynucleotides are potent immunostimulatory motifs in activating both innate and acquired immune system by inducing Th1 type antigen-specific T cell responses, but their instability in serum greatly influences their immunostimulant efficiency. Here, we constructed a novel immuno-DNA nanohydrogels consisting of tandem repeat sequences of CpG units named CpG-MCA nanohydrogels through multi-primed chain amplification. CpG-MCA nanohydrogels were proved to resist degradation and increase the proliferation and migration of murine macrophage-like RAW264.7 cells. Furthermore, CpG-MCA nanohydrogels effectively induced high expression of tumor necrosis factor-α and interleukin-6, and remarkably inhibited the proliferation of U251 cells, suggesting that CpG-MCA nanohydrogels are expected to be employed as the potent anti-cancer immunostimulant. Electronic supplementary material The online version of this article (10.1186/s11671-019-3032-9) contains supplementary material, which is available to authorized users.

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Liposomal CpG-ODN: An in vitro and in vivo study on macrophage subtypes responses, biodistribution and subsequent therapeutic efficacy in mice models of cancers

Cited by 43 publications

References 42 publications

Optimization of Docetaxel Loading Conditions in Liposomes: proposing potential products for metastatic breast carcinoma chemotherapy

Optimization of Docetaxel Loading Conditions in Liposomes: proposing potential products for metastatic breast carcinoma chemotherapy

Design of a novel vaccine nanotechnology-based delivery system comprising CpGODN-protein conjugate anchored to liposomes

Potent anti-tumor immunostimulatory biocompatible nanohydrogel made from DNA

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