Research Article – Pharmaceutical NanotechnologyTumor-Targeted Paclitaxel Delivery and Enhanced Penetration Using TAT-Decorated Liposomes Comprising Redox-Responsive Poly(Ethylene Glycol)
Section snippets
INTRODUCTION
Nanotechnology-based targeted drug delivery systems have drawn much attention for improved efficacy and reduced toxicity by reducing side effects resulted from non-specific tissue distribution of free therapeutic molecules.1 To date, many nanocarriers have been prepared, such as micelles,2., 3. nanoparticles,4., 5. liposomes,6., 7. and so on. Liposomes have shown promising results in clinical and preclinical studies such as Doxil8 and DaunoXome,9 owing to their good biocompatibility, ease of
Materials
Paclitaxel was purchased from AP Pharmaceutical Company, Ltd. (Chongqing, China). Soybean phosphatidylcholine (SPC) was purchased from Shanghai Taiwei Chemical Company (Shanghai, China). Cholesterol (CHO) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) were purchased from Chengdu Kelong Chemical Company (Chengdu, China). Reduced GSH was purchased from Merck & Company, Inc. (Whitehouse Station, New Jersey).
Characterization of Liposomes
All liposomes exhibited a mean particle size between 100.43 and 113.10 nm and an average polydispersity index between 0.215 and 0.270 (Table 2), being adequate for a passive targeting based on EPR effect as the effective drug delivery using liposomes by EPR effect is highly dependent on size ranging from 100 to 200 nm in diameter.42 Compared with the positive potential of PTX-TAT-LP, PTX-C-TAT-LP showed a negative zeta potential (Table 2) because of the comodification of cleavable PEG on the
CONCLUSIONS
In our study, the PTX-loaded exogenous-GSH triggered TAT-presenting liposomes (PTX-C-TAT-LP) were constructed. Owing to the cleavable PEG which masks the TAT moieties, PTX-loaded liposomes have a long circulation time for enhanced tumor accumulation under normal physiologic condition. In the presence of GSH, however, PEG was removed and TAT was exposed, triggering a fast cellular uptake. The endocytosis inhibition study revealed that the active endocytosis of C-TAT-LP was mediated by
ACKNOWLEDGMENTS
This research was supported by the National Natural Science Foundation of China (81373337) and the National Basic Research Program of China (973 Program, 2013CB932504).
REFERENCES (83)
- et al.
pH-responsive release of proteins from biocompatible and biodegradable reverse polymer micelles
J Control Release
(2014) - et al.
siRNA delivery from triblock copolymer micelles with spatially-ordered compartments of PEG shell, siRNA-loaded intermediate layer, and hydrophobic core
Biomaterials
(2014) - et al.
Glioma-homing peptide with a cell-penetrating effect for targeting delivery with enhanced glioma localization, penetration and suppression of glioma growth
J Control Release
(2013) - et al.
pH-Responsive polymer-liposomes for intracellular drug delivery and tumor extracellular matrix switched-on targeted cancer therapy
Biomaterials
(2014) - et al.
Thermally triggered release of a pro-osteogenic peptide from a functionalized collagen-based scaffold using thermosensitive liposomes
J Control Release
(2014) Doxil ®—The first FDA-approved nano-drug: Lessons learned
J Control Release
(2012)- et al.
Increased tumor targeted delivery using a multistage liposome system functionalized with RGD, TAT and cleavable PEG
Int J Pharm
(2014) - et al.
The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect
Adv Drug Deliv Rev
(2011) - et al.
A multifunctional envelope type nano device (MEND) for gene delivery to tumours based on the EPR effect: A strategy for overcoming the PEG dilemma
Adv Drug Deliv Rev
(2011) - et al.
Systemic delivery of siRNA to tumors using a lipid nanoparticle containing a tumor-specific cleavable PEG-lipid
Biomaterials
(2011)
Cell-penetrating peptides: Mechanism and kinetics of cargo delivery
Adv Drug Deliv Rev
FGFR-targeted gene delivery mediated by supramolecular assembly between $-cyclodextrin-crosslinked PEI and redox-sensitive PEG
Biomaterials
Toward synthetic viruses: Endosomal pH-triggered deshielding of targeted polyplexes greatly enhances gene transfer in vitro and in vivo
Mol Ther
Masking and triggered unmasking of targeting ligands on nanocarriers to improve drug delivery to brain tumors
Biomaterials
p53 mediated apoptosis by reduction sensitive shielding ternary complexes based on disulfide linked PEI ternary complexes
Biomaterials
Biological evaluation of new antitumor taxoids: Alteration of substitution at the C-7 and C-10 of docetaxel
Bioorg Med Chem Lett
The paradox of paclitaxel neurotoxicity: Mechanisms and unanswered questions
Neuropharmacol
Paclitaxel and its formulations
Int J Pharm
A pH-responsive α-helical cell penetrating peptide-mediated liposomal delivery system
Biomaterials
The efficiency of tumor-specific pH-responsive peptide-modified polymeric micelles containing paclitaxel
Biomaterials
Paclitaxel loaded liposomes decorated with a multifunctional tandem peptide for glioma targeting
Biomaterials
The use of cholesterol-containing biodegradable block copolymers to exploit hydrophobic interactions for the delivery of anticancer drugs
Biomaterials
Preparation and in vitro anticancer activity of wheat germ agglutinin (WGA)-conjugated PLGA nanoparticles loaded with paclitaxel and isopropyl myristate
J Control Release
Intracellular targeting delivery of liposomal drugs to solid tumors based on EPR effects
Adv Drug Deliv Rev
Cell-penetrating and cell-targeting peptides in drug delivery
Biochim Biophys Acta
Enhanced solubility and stability of PEGylated liposomal paclitaxel: In vitro and in vivo evaluation
Int J Pharm
Plasma membrane poration induced by ultrasound exposure: Implication for drug delivery
J Control Release
Immunotoxicity derived from manipulating leukocytes with lipid-based nanoparticles
Adv Drug Deliv Rev
Multicellular tumor spheroids: An underestimated tool is catching up again
J Biotechnol
Glioma therapy using tumor homing and penetrating peptide-functionalized PEG–PLA nanoparticles loaded with paclitaxel
Biomaterials
The effect of actin disrupting agents on contact guidance of human embryonic stem cells
Biomaterials
Hepatitis B virus preS1-derived lipopeptide functionalized liposomes for targeting of hepatic cells
Biomaterials
Challenges in design of translational nanocarriers
J Control Release
Role of clathrin-and caveolae-mediated endocytosis in gene transfer mediated by lipo-and polyplexes
Mol Ther
Investigating the uptake and intracellular fate of pH-sensitive liposomes by flow cytometry and spectral bio-imaging
J Control Release
Monitoring the transport of polymeric micelles across MDCK cell monolayer and exploring related mechanisms
J Control Release
A rapid method for measuring apoptosis and dual-color immunofluorescence by single laser flow cytometry
J Immunol Methods
Stealth nanoparticles: High density but sheddable PEG is a key for tumor targeting
J Control Release
‘Stealth’corona-core nanoparticles surface modified by polyethylene glycol (PEG): Influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption
Colloids Surf B Biointerfaces
Reduction-triggered delivery using nucleoside-lipid based carriers possessing a cleavable PEG coating
J Control Release
Redox-sensitive micelles self-assembled from amphiphilic hyaluronic acid-deoxycholic acid conjugates for targeted intracellular delivery of paclitaxel
Biomaterials
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