A Heat‐Activated Drug‐Delivery Platform Based on Phosphatidyl‐(oligo)‐glycerol Nanocarrier for Effective Cancer Treatment

Abstract

The potential of cancer drugs is not fully exploited due to low tumor uptake and occurrence of systemic side effects, limiting maximum tolerated dose. Actively targeted nanocarriers improve efficacy while minimizing off‐target toxicity. Herein, it is the first time a drug‐delivery platform for heat‐triggered intravascular drug release is described, based on synthetic phosphatidyl‐(oligo)‐glycerols from organic synthesis to preclinical investigation in feline patients. For the nanocarrier formulated doxorubicin (DOX), superior tumor drug delivery and antitumor activity compared with free DOX, conventional liposomal DOX (Caelyx), and temperature‐sensitive lysolipid‐containing DOX‐liposomes in rat sarcoma are demonstrated. In a comparative oncological study with neoadjuvant treatment of feline sarcoma, a metabolic response determined with 18 F‐FDG‐positron emission tomography/magnetic resonance imaging (PET/MRI) and histopathological response after tumor resection are significantly better compared with free DOX, potentially by overcoming drug resistance based on improved intratumoral drug distribution. This novel drug‐delivery platform has great potential for the treatment of locally advanced tumors in humans.

DPPG2-based thermosensitive liposomes as drug delivery system for effective muscle-invasive bladder cancer treatment in vivo

“…In humans, T2-T4 bladder tumors are generally found on the lateral (39%) or posterior wall (19%) [40] and T2 tumors have a median tumor size of 3.0 cm [41]. Despite obvious differences between rats and humans, we believe that the application of DPPG 2 -TSL with HT has potential for MIBC T2-T4a because the working mechanism of the nanocarriers is exploiting heat-triggered vascular drug release [42]. Up to date, experience with HT for MIBC only exists using the deep regional HT method (only with very small sample sizes) [43,44], not yet with intravesical HT.…”

Recent Preclinical and Clinical Progress in Liposomal Doxorubicin

“…It was shown that DOX leakage from DPPG-TSL did not exceed 5% after 1 h of incubation in serum at 37 °C compared to approximately 30% leakage from LTLD. Furthermore, DPPG-TSL exhibited a DOX release profile similar to LTLD at 42 °C in vitro, indicating that the fast and complete release of DOX can be achieved without the inclusion of lysolipids [ 129 , 130 ].…”

“…Hossann et al revealed that DOX accumulation was higher in tumors but lower in the heart of sarcoma-bearing rats after treatment with DPPG-TSLDOX+ HT compared to LTLD+ HT. Consequently, rats treated with DPPG-TSL had the highest survival rate [ 130 ]. Similarly, DPPG-TSLDOX was evaluated in cats suffering from feline sarcoma [ 130 , 131 ].…”

Size effect of liposomes on centimeter-deep ultrasound-switchable fluorescence imaging and ultrasound-controlled release

“…For example, doxorubicin (DOX)-encapsulated liposomes were used for targeted drug delivery. [18][19][20] However, the lack of drug release control is considered an issue. 21 Ultrasound-mediated drug release of liposomes is one of the potential solutions for overcoming this barrier.…”