NIR responsive liposomal system for rapid release of drugs in cancer therapy

Abstract

To design a rapid release liposomal system for cancer therapy, a NIR responsive bubble-generating thermosensitive liposome (BTSL) system combined with photothermal agent (Cypate), doxorubicin (DOX), and NH 4 HCO 3 was developed. Cypate/DOX-BTSL exhibited a good aqueous stability, photostability, and photothermal effect. In vitro release suggested that the amounts of DOX released from BTSL were obviously higher than that of (NH 4 ) 2 SO 4 liposomes at 42°C. After NIR irradiation, the hyperthermic temperature induced by Cypate led to the decomposition of NH 4 HCO 3 and the generation of a large number of CO 2 bubbles, triggering a rapid release of drugs. Confocal laser scanning microscope and acridine orange staining indicated that Cypate/DOX-BTSL upon irradiation could facilitate to disrupt the lysosomal membranes and realize endolysosomal escape into cytosol, improving the intracellular uptake of DOX clearly. MTT and trypan blue staining implied that the cell damage of Cypate/DOX-BTSL with NIR irradiation was more severe than that in the groups without irradiation. In vivo results indicated that Cypate/DOX-BTSL with irradiation could dramatically increase the accumulation of DOX in tumor, inhibit tumor growth, and reduce systemic side effects of DOX. These data demonstrated that Cypate/DOX-BTSL has the potential to be used as a NIR responsive liposomal system for a rapid release of drugs in thermochemotherapy.

Real-time fluorescence imaging for visualization and drug uptake prediction during drug delivery by thermosensitive liposomes

“…These factors include the device/method of HT (since the device affects tumor temperature distribution) (19), the applied temperature, and the HT duration (11, 20, 21). Prior preclinical studies with TSL employed varying HT durations ranging from 2 to 60 min (9, 24, 12, 22, 25, 19, 26, 20), with all studies limited to a single duration except for three recent reports that examined two HT durations (11, 20, 21). In the current study we demonstrated that the amount of Dox delivered to tumors quantified by HPLC increased with HT duration, for the three durations of 15, 30 and 60 min (Fig.…”

“…In addition, the duration of HT dictates drug uptake (20, 21). Both the duration and method of HT in preclinical animal studies differ considerably, with HT duration ranging from 2 to 12 min for RFA (12, 20), 2 to 40 min for HIFU (22, 23), 60 min for heated water bath (9, 24, 25) and cold light lamp (19), and 5 to 60 min when a laser was used as heat source (19, 26).…”

Dual-Targeting and Stimuli-Triggered Liposomal Drug Delivery in Cancer Treatment

“…The wavelengths preferred in biomedical applications are in the NIR regions (∼700−1100 nm) because at this wavelength the light penetration is more than 1 cm. 72 Chen et al 95 designed a NIR responsive bubble-generating thermosensitive liposome (BTSL) system entrapping the reactive carbocyanine dye (Cypate), DOX, and NH 4 HCO 3 . Cypate is a NIR fluorescent dye with an absorbance maximum at 778 nm and an emission maximum at 805 nm with a high extinction coefficient of 224,000 (mol/L) −1 cm −1 .…”

A Promising Biocompatible Platform: Lipid-Based and Bio-Inspired Smart Drug Delivery Systems for Cancer Therapy

“…For example, laser irradiation can be used to produce fluorescence or luminescence images, and to simultaneously induce drug release [141]. Chen et al developed a near-infrared (NIR) responsive liposomal system for rapid drug release [142]. Lipid carriers containing ammonium bicarbonate and cypate dye were found to immediately generate bubbles when exposed to NIR irradiation, which enhanced lipid bilayer permeability and drug release.…”