Chemotherapeutic drug delivery to cancer cells using a combination of folate targeting and tumor microenvironment-sensitive polypeptides

Gao, Wei; Xiang, Bingren; Meng, Tao; Lin, Feng; Qi, Xian

doi:10.1016/j.biomaterials.2013.02.014

Cited by 222 publications

(127 citation statements)

References 39 publications

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“…Strategies such as using ultra-small nanoparticles [46], incorporating cell penetrating peptide (CPP) [47] or tumour penetrating peptide [48] could be used to increase tumour penetration in future studies. Therefore, liposomes incorporating both the active targeting and tumour penetration enhancement will be desirable to achieve better drug delivery efficiency.…”

Section: Cellular Uptake and Penetration Of Liposomes In Tumour Sphermentioning

confidence: 99%

Microfluidic synthesis of multifunctional liposomes for tumour targeting

Ran

Middelberg

Zhao

2016

Colloids and Surfaces B: Biointerfaces

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Graphical abstract Highlights Targeted liposomes can be prepared in the one-step microfluidic device  Size and surface properties can be controlled easily  This microfluidic method directed targeted liposomes possess selective cell uptake enhancement in both 2D and 3D model.  At the same time, these liposomes can reduce phagocytosis. AbstractNanotechnology has started a new era in engineering multifunctional nanoparticles for diagnosis and therapeutics by incorporating therapeutic drugs, targeting ligands, stimuliresponsive release and imaging molecules. However, more functionality requires more complex synthesis processes, resulting in poor reproducibility, low yield and high production cost, hence difficulties in clinical translation. Herein we report a one-step microfluidic method for making multifunctional liposomes. Three formulations were prepared using this simple method, including plain liposomes, PEGylated liposomes and folic acid functionalised liposomes, all with a fluorescence dye encapsulated for imaging. The size and surface properties of these liposomes can be precisely controlled by simply tuning the flow rate ratio and the ratio of the lipids to PEGylated lipid (DSPE-PEG2000) and to the DSPE-PEG2000-Folate, respectively. The synthesised liposomes remained stable under mimic serum conditions.Compared to the plain liposomes and PEGylated liposomes, the targeted folic acid functionalised liposomes exhibited enhanced cellular uptake by the FA receptor positive SKOV3 cells, but not the negative MCF7 cells, and this enhanced uptake could be inhibited by adding excess free folic acid, indicating high specificity of FA ligand-receptor endocytosis.Further evaluation using the 3D tumour spheroid model also showed higher internalisation of the targeted liposome formulation in comparison with the PEGylated one. To the best of our knowledge, this work demonstrates for the first time the versatility of this microfluidic method for making different liposome formulations in a single step, their superior physicochemical properties as well as the enhanced cellular uptake and tumour spheroid uptake of the targeted liposomes.

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Section: Cellular Uptake and Penetration Of Liposomes In Tumour Sphermentioning

confidence: 99%

Microfluidic synthesis of multifunctional liposomes for tumour targeting

Ran

Middelberg

Zhao

2016

Colloids and Surfaces B: Biointerfaces

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“…Tween-80 (0.5% w/v) was added in phosphate-buffered saline (PBS) (pH 7.4) as the release medium due to the poor solubility of IRI and sink condition requirement of the release test. 37 Briefly, 1 mL sample was added to the dialysis bag and incubated with 20 mL release …”

Section: In Vitro Releasementioning

confidence: 99%

Efficient co-delivery of immiscible hydrophilic/hydrophobic chemotherapeutics by lipid emulsions for improved treatment of cancer

Zhang¹,

Song²,

Wang³

et al. 2017

IJN

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Combinational nanomedicine is becoming a topic of much interest in cancer therapy, although its translation into the clinic remains extremely challenging. One of the main obstacles lies in the difficulty to efficiently co-deliver immiscible hydrophilic/hydrophobic drugs into tumor sites. The aim of this study was to develop co-loaded lipid emulsions (LEs) to co-deliver immiscible hydrophilic/hydrophobic drugs to improve cancer therapy and to explore the co-delivery abilities between co-loaded LEs and mixture formulation. Multiple oxaliplatin/irinotecan drug–phospholipid complexes (DPCs) were formulated. Co-loaded LEs were prepared using DPC technique to efficiently encapsulate both drugs. Co-loaded LEs exhibited uniform particle size distribution, desired stability and synchronous release profiles in both drugs. Co-loaded LEs demonstrated superior anti-tumor activity compared with the simple solution mixture and the mixture of single-loaded LEs. Furthermore, co-loaded nanocarriers could co-deliver both drugs into the same cells more efficiently and exhibited the optimized synergistic effect. These results indicate that co-loaded LEs could be a desired formulation for enhanced cancer therapy with potential application prospects. The comparison between co-loaded LEs and mixture formulation is significant for pharmaceutical designs aimed at co-delivery of multiple drugs.

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“…In this study, the overall targeting efficiency (TE), targeting index (TI), and relative overall targeting efficiency (RTE) were calculated to evaluate the in vivo targeting of the NGR-SWCNTPaclitaxel complex (Gao et al, 2013;Germano et al, 2013;Shahin et al, 2013). The TE indicates the percentage of tissue distribution, the TI indicates the variation in the medicine concentration between the experimental and control group tissues, and the RTE represents the relativity value of the variation.…”

Section: Analysis Of Tissue Distributionmentioning

confidence: 99%

Preparation and biological activity of a paclitaxel-single-walled carbon nanotube complex

Fu¹,

Zhang²,

Wang³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Single-walled carbon nanotubes (SWCNTs) have unique transmembrane abilities. The huge superficial area and abundance of π electrons confer SWCNTs perfect absorptive capability toward proteins, nucleates, and many drugs. These characteristics make SWCNTs a new and efficient drug carrier. The purpose of this study was to disperse SWCNTs in water and have paclitaxel absorbed onto them in order to construct an asparagine-glycine-arginine (NGR)-SWCNT-Paclitaxel complex as a targeting nanoparticle system. The NGR-SWCNTPaclitaxel complex was systematically studied, and analytical methods, including spectrophotometry for SWCNTs and high-performance liquid chromatography for paclitaxel, were employed. The preparation and the prescription of the NGR-SWCNT-Paclitaxel complex lyophilized powder were investigated. MCF-7 cancer cells, Sprague-Dawley rats, and S180 tumor-bearing mice were used as experimental subjects to evaluate the in vitro and in vivo activity of NGR-SWCNT-Paclitaxel complex dispersion. The complex dispersion showed obvious inhibition activity against MCF-7 cancer cells. Within 1 h, the NGR-SWCNT-Paclitaxel complex could be transferred to cells, and sustained the release of drugs. In addition, the tumor and liver targeting and improved therapeutic effects of the NGR-SWCNT-Paclitaxel complex were confirmed.

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Chemotherapeutic drug delivery to cancer cells using a combination of folate targeting and tumor microenvironment-sensitive polypeptides

Cited by 222 publications

References 39 publications

Microfluidic synthesis of multifunctional liposomes for tumour targeting

Microfluidic synthesis of multifunctional liposomes for tumour targeting

Efficient co-delivery of immiscible hydrophilic/hydrophobic chemotherapeutics by lipid emulsions for improved treatment of cancer

Preparation and biological activity of a paclitaxel-single-walled carbon nanotube complex

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