Novel Class of Ultrasound-Triggerable Drug Delivery Systems for the Improved Treatment of Tumors

Abstract

The controlled release of anticancer drugs at the tumor site is a central challenge in treating cancer. To achieve this goal, our strategy was based on tumor-specific targeting and ultrasound-triggered release of an anticancer agent from liposomal nanocarriers. To enhance the ultrasound-triggered drug release, we incorporated a lipophilic sonosensitizer, chlorin e6 (Ce6) ester, into the lipid bilayer of liposomes. Additionally, asparagine-glycine-arginine (NGR) that binds to CD13, which is overexpressed in tumor cells, was introduced into these liposomes. Under the navigation effects of the NGR, the novel ultrasound-triggerable NGR-modified liposomal nanocarrier (NGR/UT-L) accumulates in tumor sites. Once irradiated by ultrasound in tumor tissues, the sonodynamic effect produced by Ce6 could create more efficient disruptions of the lipid bilayer of the liposomal nanocarriers. After encapsulating doxorubicin (DOX) as the model drug, the ultrasound triggered lipid bilayer breakdown can spring the immediate release of DOX, making it possible for ultrasound-responsive chemotherapy with great selectivity. By combining tumor-specific targeting and stimuli-responsive controlled release into one system, NGR/UT-L demonstrated a perfect antitumor effect. Moreover, this report provides an example of controlled-release by means of a novel class of ultrasound triggering systems.

Nanomedicine in cancer therapy: promises and hurdles of polymeric nanoparticles

“…Specific characteristics of the tumor microenvironment and endosomes, including the acidic pH and metabolic products, have been exploited to trigger drug release. Furthermore, nanoparticles that release their cargo upon external stimuli such as exposure to ultrasound, light, temperature, or magnetic fields have shown promising as controlled drug release systems [59][60][61][62][63][64].…”

The Current Status of Chlorin e6-Based Nanoscale Delivery Systems for Cancer Therapy

“…Triggered release liposomes came into being, an intelligent system that releases drugs for local administration in response to external stimuli. Zhou and colleagues use ultrasound to trigger the release of drugs and enhance controlled-release and storage stability [28]. They designed a particular liposomal drug delivery system that mixed lipophilic Ce6 with lipids to synthesize ultrasound-triggered liposomes (UT-L).…”

Organic Nanocarriers for Delivery and Targeting of Therapeutic Agents for Cancer Treatment

“…Ultrasound has been used as an external trigger to release the cargoes from the nanocarrier systems. Sonodynamic therapy (SDT) is considered as an alternative to PDT, where chromophores such as Ce6 strongly absorb ultrasound and generate ROS . In this section, we have discussed a few examples where ultrasound is utilized for triggered drug release from the nanoformulations for cancer treatment.…”

“…developed CD13 receptor‐targeted liposomes which incorporate chlorin e6 (Ce6) ester in the lipophilic bilayer membrane as a sonosensitizer and encapsulating DOX in the inner core. After liposome accumulation in tumor sites, ultrasound was applied to the tumor tissues, Ce6 could breakdown the lipid bilayer and resulted in the release of DOX …”