The performance of expansile nanoparticles in a murine model of peritoneal carcinomatosis.
Carcinomatosis from peritoneal surface malignancies, such as mesothelioma, appendiceal carcinoma or ovarian metastases, significantly decreases survival and quality of life. Given a 60-80% locoregional recurrence rate after surgical debulking for mesothelioma, the current study explores the use of polymeric nanoparticles, specifically engineered to expand and locally deliver chemotherapeutic agents at endosomal pH, for the prevention of progressive carcinomatosis. Anti-tumor efficacy of paclitaxel-loaded pH-responsive expansile nanoparticles (Pax-eNP) was evaluated in vitro and in in vivo murine models of malignant peritoneal mesothelioma. Pax-eNP inhibited mesothelioma growth in vitro, markedly decreased tumor growth and disease severity in vivo, prevented initial intraperitoneal tumor implants, and significantly prolonged survival compared to other intraperitoneal drug delivery methods. These outcomes suggest that the mechanism of pH-triggered drug delivery and tumor affinity associated with eNP may effectively improve the local control of residual microscopic disease following surgical debulking of locoregionally aggressive malignancies.
Division of Thoracic Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA. ycolson@partners.org
Yolonda L
YL
Colson
Rong
R
Liu
Emily B
EB
Southard
Morgan D
MD
Schulz
Jacqueline E
JE
Wade
Aaron P
AP
Griset
Kimberly Ann V
KA
Zubris
Robert F
RF
Padera
Mark W
MW
Grinstaff
D000418:Albumins / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D017239:Paclitaxel / Q000627:therapeutic use*; D010534:Peritoneal Neoplasms / Q000188:drug therapy*
C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D000970:Antineoplastic Agents; D017239:Paclitaxel