Theranostic Liposome–Nanoparticle Hybrids for Drug Delivery and Bioimaging

Abstract

Advanced theranostic nanomedicine is a multifunctional approach which combines the diagnosis and effective therapy of diseased tissues. Here, we investigated the preparation, characterization and in vitro evaluation of theranostic liposomes. As is known, liposome-quantum dot (L-QD) hybrid vesicles are promising nanoconstructs for cell imaging and liposomal-topotecan (L-TPT) enhances the efficiency of TPT by providing protection against systemic clearance and allowing extended time for it to accumulate in tumors. In the present study, hydrophobic CdSe/ZnS QD and TPT were located in the bilayer membrane and inner core of liposomes, respectively. Dynamic light scattering (DLS), zeta potential (ζ) measurements and fluorescence/absorption spectroscopy were performed to determine the vesicle size, charge and spectroscopic properties of the liposomes. Moreover, drug release was studied under neutral and acidic pH conditions. Fluorescence microscopy and flow cytometry analysis were used to examine the cellular uptake and intracellular distribution of the TPT-loaded L-QD formulation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was utilized to investigate the in vitro cytotoxicity of the formulations on HeLa cells. According to the results, the TPT-loaded L-QD hybrid has adequate physicochemical properties and is a promising multifunctional delivery vehicle which is capable of a simultaneous co-delivery of therapeutic and diagnostic agents.

Rapid Microfluidic Preparation of Niosomes for Targeted Drug Delivery

“…The zeta potential of the bare niosomes was measured as −27.80 mV. TPT loading did not significantly influence the zeta potential of the plain vesicles (−27.00 mV) as a result of any TPT intercalation in the vesicle membrane [7]. Conjugation of tLyp-1 increased the hydrodynamic diameter of niosome, corresponding to the presence of the peptide on the niosomal surface.…”

“…TPT release profiles from PEGNIO/TPT/tLyp-1 showed a faster release of TPT under acidic environments than that at neutral pH (Figure 2). This can be explained by increasing solubility of TPT with decreasing pH as a result of protonation [7,41]. Moreover, the quantity of released TPT was significantly enhanced at pH 5.6, and there seemed to be a saturation effect under neutral conditions.…”

“…The major limitation of this drug is that TPT is unstable in physiological conditions and undergoes a pH-dependent rapid and reversible hydrolysis from a closed lactone ring to the inactive carboxylated open-ring form, which causes the loss of the antitumor activity of the drug [4]. To protect TPT from hydrolysis, the encapsulation into different types of nanoparticles such as liposomes, lipid nanoparticles, and mesoporous silica has been presented [5,6,7,8].…”

<p>Review of the Application of Nanovesicles and the Human Interstitial Fluid in Gastrointestinal Premalignant Lesion Detection, Diagnosis, Prognosis and Therapy</p>

“…These hybrid NVs can be used for accurate cancer diagnosis and monitoring. QDs can be implanted on the bilayer membrane surface or inner core of the vesicle to form conjugated NVs, which can be labeled with fluorescent QDs and tracked by specific marker antibodies89 to define their physical characteristics and determine their concentration 90. NVs that are synthesized through the sol-gel method possess hydrophilic and hydrophobic microdomains, which enable the co-delivery of both water-soluble and water-insoluble drugs for maximum anti-tumor efficacy 89.…”

“…QDs can be implanted on the bilayer membrane surface or inner core of the vesicle to form conjugated NVs, which can be labeled with fluorescent QDs and tracked by specific marker antibodies89 to define their physical characteristics and determine their concentration 90. NVs that are synthesized through the sol-gel method possess hydrophilic and hydrophobic microdomains, which enable the co-delivery of both water-soluble and water-insoluble drugs for maximum anti-tumor efficacy 89. For example, the topotecan (TPT)-loaded liposome-QD hybrid was shown to be able to transport both therapeutic and diagnostic agents simultaneously, thereby functioning as a multifunctional delivery vehicle 89.…”