A novel intralymphatic nanocarrier delivery system for cisplatin therapy in breast cancer with improved tumor efficacy and lower systemic toxicity in vivo.
BACKGROUND
A lymphatically delivered nanoconjugate of cisplatin was evaluated in an orthotopic mouse model of locoregionally metastatic breast cancer (LABC) to determine if it can overcome some of the limitations of standard cisplatin therapy such as high systemic toxicity.


METHODS
Human breast cancer cells (10(7) MDA-MB-468LN) were injected into the mammary fat pad of female nu/nu mice. Once tumor volume reached 50 mm(3), intravenous cisplatin or subcutaneous hyaluronan-cisplatin (HA-cisplatin) nanoconjugate was given 1/week x 3 weeks at 3.3 mg/kg (platinum basis).


RESULTS
Nanoconjugates colocalized with the tumors after subcutaneous peritumoral injection and showed improved efficacy to intravenous cisplatin. After 1 month, renal tubular hemorrhage and edema were more prevalent in the intravenous formulation compared with subcutaneous HA-cisplatin nanoconjugates.


CONCLUSIONS
This nanocarrier delivery platform focuses on delivering drugs to the areas in which tumor burden is greatest, potentially reducing systemic toxicity, and has future applicability as a neoadjuvant or adjuvant therapy for LABC.
Cohen
Mark S
MS
Department of Surgery, University of Kansas, Medical Center, Kansas City, KS, USA.
Cai
Shuang
S
Xie
Yumei
Y
Forrest
M Laird
ML
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D008208:Lymphatic System; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D009368:Neoplasm Transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000970:Antineoplastic Agents; D002945:Cisplatin