Codelivery of doxorubicin and triptolide with reduction-sensitive lipid-polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment.
Codelivery is a promising strategy to overcome the limitations of single chemotherapeutic agents in cancer treatment. Despite progress, codelivery of two or more different functional drugs to increase anticancer efficiency still remains a challenge. Here, reduction-sensitive lipid-polymer hybrid nanoparticles (LPNPs) drug delivery system composed of monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16), soybean lecithin, and poly(D,L-lactide-co-glycolide) (PLGA) was used for codelivery of doxorubicin (DOX) and a Chinese herb extract triptolide (TPL). Hydrophobic DOX and TPL could be successfully loaded in LPNPs by self-assembly. More importantly, drug release and cellular uptake experiments demonstrated that the two drugs were reduction sensitive, released simultaneously from LPNPs, and taken up effectively by the tumor cells. DOX/TPL-coloaded LPNPs (DOX/TPL-LPNPs) exhibited a high level of synergistic activation with low combination index (CI) in vitro and in vivo. Moreover, the highest synergistic therapeutic effect was achieved at the ratio of 1:0.2 DOX/TPL. Further experiments showed that TPL enhanced the uptake of DOX by human oral cavity squamous cell carcinoma cells (KB cells). Overall, DOX/TPL-coencapsulated reduction-sensitive nanoparticles will be a promising strategy for cancer treatment.
Department of Radiology, Zhongnan Hospital of Wuhan University; Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, People's Republic of China.
Bo
B
Wu
Department of Radiology, Zhongnan Hospital of Wuhan University.
Shu-Ting
ST
Lu
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, People's Republic of China.
Liu-Jie
LJ
Zhang
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, People's Republic of China.
Ren-Xi
RX
Zhuo
Department of Radiology, Zhongnan Hospital of Wuhan University.
Hai-Bo
HB
Xu
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, People's Republic of China.
Shi-Wen
SW
Huang
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000008:administration & dosage* / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D004357:Drug Synergism; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D005434:Flow Cytometry; D006801:Humans; D019344:Lactic Acid; D008055:Lipids / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy*; D010084:Oxidation-Reduction / Q000187:drug effects; D010316:Particle Size; D010616:Phenanthrenes / Q000008:administration & dosage* / Q000627:therapeutic use*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D000970:Antineoplastic Agents; D004224:Diterpenes; D004852:Epoxy Compounds; D008055:Lipids; D010616:Phenanthrenes; C001899:triptolide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin
codelivery; reduction sensitive; synergistic effect; triptolide