alternately adsorbed onto the templateviaa layer-by-layer technique, to render CMCS-cationic liposome-coated DNA/protamine/DNA complexes (CLDPD).
In vitro test with isolated tumor (HepG2) cells and in vivo evaluation into tumor-bearing mice confirmed the transfection efficiency. Other reports also confirmed the relevance of the fusogenic properties of the pH-sensitive liposomal membranes for intra-cellular gene transfection.43–45
The pH-sensitive stealth liposomes have been reported as suitable vectors for targeting therapeutic peptides to the nucleous.46 Cellular uptake of peptide- loaded liposomes has been investigated in Hs578t human epithelial cells from breast carcinoma, MDA-MB-231 human breast carcinoma cells and WI-26 human diploid lung fibroblast cells. Two different formulations were tested:
long circulating classical liposomes [soybean phosphatidylcholine : CHOL : PEG-750-DSPE (47 : 47 : 6 molar% ratio)] and pH-sensitive stealth liposomes [DOPE : CHEMS : CHOL : PEG750-DSPE (43 : 21 : 30 : 6 molar% ratio)]. The difference between both formulations in terms of peptide delivery from the endosome to the cytoplasm and even to the nucleus was observed as a function of time. Using pH-sensitive stealth liposomes, the peptide was able to reach the nucleus of tumorigenic and non-tumorigenic breast cancer cells.46In summary, the available information demonstrates the utility of pH-sensitive liposomes as intra-cellular carrier for bioactives.
3.4.3 Tumor Diagnosis
Liposomes are excellent candidates for the development of theranostic agents and multi-modal imaging probes, since they can release the entrapped imaging probe/radioactive agent/drug in response to a change of physico-chemical variables like pH, redox potential or concentration of specific enzymes that usually occur in the early asymptomatic stage of several diseases such as cancer.47 The pH-sensitive liposomes trapping 99mTc have been used for biodistribution studies and scintigraphic imaging in Ehrlich tumor-bearing mice. They accumulate in tumor tissue with high tumor-to-muscle ratio and can be useful for diagnosis of tumors.48
Paramagnetic pH-sensitive liposomes have also been developed as imaging tools for visualizing drug-delivery and release processes by means of Magnetic Resonance Imaging (MRI). The proposed formulation allowed the fast and full release of gadoteridol at pH 5.5. The leakage of the imaging reporter from the vesicles was associated with a relaxivity enhancement that allowed its visual- ization by MRI. It was observed that the release mechanism implies the protonation of the basic sites that leads to vesicle aggregation, thus enabling the expression of the fusogenic property.49
in nanomedicine and nanobiotechnology dealing with tumor and cardio- vascular diseases. Particularly, the pH-sensitive liposomes enable efficient intra- cellular delivery of drugs and genes. Furthermore, most components used for their design have been proved to be safe, which may pave the way for the approval and commercialization of pH-sensitive liposomes.
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