Thermosensitive, Near-Infrared-Labeled Nanoparticles for Topotecan Delivery to Tumors

TY - JOUR

T1 - Thermosensitive, Near-Infrared-Labeled Nanoparticles for Topotecan Delivery to Tumors

AU - Rosca, Elena V.

AU - Wright, Michael

AU - Gonitel, Roman

AU - Gedroyc, Wladyslaw

AU - Miller, Andrew D.

AU - Thanou, Maya

PY - 2015/5/4

Y1 - 2015/5/4

N2 - Liposomal nanoparticles have proven to be versatile systems for drug delivery. However, the progress in clinic has been slower and less efficient than expected. This suggests a need for further development using carefully designed chemical components to improve usefulness under clinical conditions and maximize therapeutic effect. For cancer chemotherapy, PEGylated liposomes were the first nano-medicine to reach the market and have been used clinically for several years. Approaches toward targeted drug delivery using next generation "thermally triggered" nanoparticles are now in clinical trials. However, clinically tested thermosensitive liposomes (TSLs) lack the markers that allow tumor labeling improved imaging for tissue specific applied hyperthernia. Here we describe the development of optically labeled TSLs for image guidance drug delivery and proof-of-concept results for their application in the treatment of murine xenograft tumors using the anticancer drug topotecan. These labeled TSLs also allow the simultaneous, real-time diagnostic imaging of nanoparticle biodistribution using a near-infrared (NIR; 750-950 nm) fluorophore coupled to a lipidic component of the lipid bilayer. When combined with multispectral fluorescence analysis, this allows for specific and high sensitivity tracking of the nanoparticles in vivo. The application of NIR fluorescence-labeled TSLs could have a transformative effect on future cancer chemotherapy.

AB - Liposomal nanoparticles have proven to be versatile systems for drug delivery. However, the progress in clinic has been slower and less efficient than expected. This suggests a need for further development using carefully designed chemical components to improve usefulness under clinical conditions and maximize therapeutic effect. For cancer chemotherapy, PEGylated liposomes were the first nano-medicine to reach the market and have been used clinically for several years. Approaches toward targeted drug delivery using next generation "thermally triggered" nanoparticles are now in clinical trials. However, clinically tested thermosensitive liposomes (TSLs) lack the markers that allow tumor labeling improved imaging for tissue specific applied hyperthernia. Here we describe the development of optically labeled TSLs for image guidance drug delivery and proof-of-concept results for their application in the treatment of murine xenograft tumors using the anticancer drug topotecan. These labeled TSLs also allow the simultaneous, real-time diagnostic imaging of nanoparticle biodistribution using a near-infrared (NIR; 750-950 nm) fluorophore coupled to a lipidic component of the lipid bilayer. When combined with multispectral fluorescence analysis, this allows for specific and high sensitivity tracking of the nanoparticles in vivo. The application of NIR fluorescence-labeled TSLs could have a transformative effect on future cancer chemotherapy.

KW - thermosensitive liposomes

KW - topotecan

KW - anticancer

KW - focused ultrasound

KW - multispectral fluorescence imaging

KW - INTENSITY FOCUSED ULTRASOUND

KW - TEMPERATURE-SENSITIVE LIPOSOMES

KW - TARGETED DRUG-DELIVERY

KW - IN-VIVO

KW - MILD HYPERTHERMIA

KW - SOLID TUMORS

KW - ENHANCED PERMEABILITY

KW - ANTITUMOR-ACTIVITY

KW - CONTROLLED-RELEASE

KW - TRIGGERED RELEASE

U2 - 10.1021/mp5002679

DO - 10.1021/mp5002679

M3 - Article

SN - 1543-8384

VL - 12

SP - 1335

EP - 1346

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

IS - 5

ER -