Tyroservatide-TPGS-paclitaxel liposomes: Tyroservatide as a targeting ligand for improving breast cancer treatment

doi:10.1016/j.nano.2016.10.017

Nanomedicine: Nanotechnology, Biology and Medicine

Volume 13, Issue 3, April 2017, Pages 1105-1115

https://doi.org/10.1016/j.nano.2016.10.017 Get rights and content

Abstract

Tyroservatide (YSV) is a tripeptide that has been approved for clinical testing, as a new anticancer drug. In the current study, YSV-stearic acid (YSV-SA) was inserted into the surface of d-alpha-tocopheryl polyethylene glycol 1000 succinate monoester (TPGS)-modified paclitaxel (PTX) liposomes (TP-Lip) to form YSV-conjugated TP-Lip (TYP-Lip). Both in vivo imaging and in vitro cell uptake analysis indicated that these modifications could increase tumor-targeting and cell uptake of the liposomes. Optimal antitumor effects were achieved via tail vein injections of TYP-Lip in MB-231 tumor-bearing nude mice. Overall, the formed TYP-Lip not only achieved a synergistic anticancer effect through YSV and PTX, but also improved tumor-targeting and exhibited further antitumor capabilities. These results indicated that combining biological (YSV) and chemotherapeutic (PTX) agents is an efficient combinatorial delivery strategy for enhanced tumor targeting and synergistic antitumor effects.

Graphical Abstract

1
Tyroservatide is an effective targeting ligand for breast cancer treatment.
2
TYP-Lip is a promising strategy that combines tyroservatide-targeting with a well-known paclitaxel into a single nanovehicle for co-delivery with targeted and synergistic effects.
3
This co-delivery approach enhanced efficacy and reduced toxicity both in vitro and in vivo.

Section snippets

Materials

YSV and YSV-SA were synthesized according to standard solid phase peptide synthesis processes by Shanghai ZiYu Biotech Co, Ltd. (Shanghai, China). PTX was purchased from Aladdin Scientific Inc. (Shanghai, China). Egg yolk lecithin was purchased from Shanghai Advanced Vehicle Technology Ltd. Co. (Shanghai, China). The reagents 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR), coumarin 6 (C6), amiloride, nystatin, and hypertonic sucrose were purchased from Aladdin Scientific

In vivo imaging

As seen in Figure 1, A and Supplementary Figure 1 (performed again), in vivo fluorescent optical imaging revealed weak fluorescence intensity in the tumor tissue for DiR-T-Lip group, which was increased after YSV modification. Meanwhile, the fluorescence of DiR-TY-Lip (2% YSV) was targeted to the tumor at 2 h and reached a peak at 12 h, thereby achieving the best tumor targeting. However, DiR-TY-Lip (1% and 5% YSV) groups did not show stronger targeting to the tumor versus the liver. The weak

Discussion

Liposomes have shown promising potential for targeted delivery of anticancer drugs in clinical use, such as paclitaxel, doxorubicin, and vincristine.31, 32 Moreover, the large surfaces of liposomes make them modifiable, which can lend functionalities such as accurate active targeting, long retention time, and high permeability.33, 34, 35, 36 Thus, here T-Lip were tested for PTX delivery and their antitumor effect toward breast cancer cells was evaluated. To inhibit tumors efficiently, both YSV

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A subsequent cytotoxic capacity in the 4T1 cells was noted which was further corroborated in the in vivo studies (Song et al., 2015). A synergism between tyroservatide (YSV), a tripeptide that adversely affects the proliferation, invasion and adhesion of tumor cells, and PTX were explored by Jin et al. (2016). TPGS-stearic acid conjugated liposomes were formulated to also investigate the competence of YSV-stearic acid for efficient tumor targeting.
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: Conflict of interest: There are no disclosures or any conflict of interests.

: Funding sources: This study was supported by the National Natural Science Foundation projects of China (Grant No. 81403119), 333 project of Jiangsu Province and the Science and Technology Support Project of Suqian (S210520).

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Original ArticleTyroservatide-TPGS-paclitaxel liposomes: Tyroservatide as a targeting ligand for improving breast cancer treatment

Abstract

Graphical Abstract

Section snippets

Materials

In vivo imaging

Discussion

Ann Oncol

Colloids Surf B Biointerfaces

Eur J Pharm Biopharm

Int J Pharm

Biomaterials

Trends Biotechnol

Nanomedicine

Clin Lung Cancer

Maturitas

Nanomedicine

J Biol Chem

Colloids Surf B Biointerfaces

Trends Biotechnol

Nanomedicine

Nanomedicine

Biomaterials

J Control Release

Prog Lipid Res

Adv Drug Deliv Rev

Global cancer statistics, 2012

CA Cancer J Clin

Paclitaxel-induced cell death: where the cell cycle and apoptosis come together

Cancer

A hyaluronic acid-taxol antitumor bioconjugate targeted to cancer cells

Biomacromol

Original Article
Tyroservatide-TPGS-paclitaxel liposomes: Tyroservatide as a targeting ligand for improving breast cancer treatment