Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles.
OBJECTIVE
Two unexplored aspects for irinotecan and cisplatin (I&C) combination chemotherapy are: actively targeting both drugs to a specific diseased cell type, and delivering both drugs on the same vehicle to ensure their synchronized entry into the cell at a well-defined ratio. In this work, the authors report the use of targeted polymeric nanoparticles (NPs) to coencapsulate and deliver I&C to cancer cells expressing the prostate-specific membrane antigen.


METHODS
Targeted NPs were prepared in a single step by mixing four different precursors inside microfluidic devices.


RESULTS
I&C were encapsulated in 55-nm NPs and showed an eightfold increase in internalization by prostate-specific membrane antigen-expressing LNCaP cells compared with nontargeted NPs. NPs coencapsulating both drugs exhibited strong synergism in LNCaP cells with a combination index of 0.2.


CONCLUSIONS
The strategy of coencapsulating both I&C in a single NP targeted to a specific cell type could potentially be used to treat different types of cancer.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Pedro M
PM
Valencia
Eric M
EM
Pridgen
Brian
B
Perea
Suresh
S
Gadde
Christopher
C
Sweeney
Philip W
PW
Kantoff
Neil H
NH
Bander
Stephen J
SJ
Lippard
Robert
R
Langer
Rohit
R
Karnik
Omid C
OC
Farokhzad
D000954:Antigens, Surface / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004357:Drug Synergism; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism; D006801:Humans; D000077146:Irinotecan; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000954:Antigens, Surface; D000970:Antineoplastic Agents; D011108:Polymers; D000077146:Irinotecan; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D002945:Cisplatin; D002166:Camptothecin