Superior antitumor efficiency of cisplatin-loaded nanoparticles by intratumoral delivery with decreased tumor metabolism rate.
cis-Dichlorodiamminoplatinum (II) (cisplatin) has demonstrated extraordinary activities against a variety of solid tumors. However, the clinical efficacy is contrasted by its toxicity profile. To reduce the toxicity and enhance the circulation time of cisplatin, core-shell structure nanoparticles were prepared from block copolymer of methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL). Cisplatin was incorporated into the nanoparticles with high encapsulation efficiency more than 75%. Controlled release of cisplatin was observed in a sustained manner. In vitro cytotoxicity studies proved the efficacy of cisplatin-loaded nanoparticles against BGC823 and H(22) cells in a dose and time-dependent manner. Furthermore, intratumoral administration was applied to improve the tumor-targeted delivery in the in vivo evaluation. Compared with free cisplatin, cisplatin-loaded nanoparticles exhibited superior antitumor effect by delaying tumor growth when delivered intratumorally, while no significant improvement was observed when they were administrated intraperitoneally. Positron emission tomography/computed tomography (PET/CT) imaging was utilized for the first time to detect the declined (18)F-labeled 2-fluoro-2-deoxy-d-glucose ((18)F-FDG) uptake of the tumor in mice receiving cisplatin-loaded nanoparticles intratumorally. These results suggest that polymeric nanoparticles with core-shell structures are promising for further studies as drug delivery carriers, and intratumoral delivery of drug-loaded nanoparticles could be a probable clinically useful therapeutic regimen.
Li
Xiaolin
X
Department of Oncology, Drum Tower Hospital Affiliated to Nanjing Medical University, Nanjing, 210008, PR China.
Li
Rutian
R
Qian
Xiaoping
X
Ding
Yitao
Y
Tu
Yunxia
Y
Guo
Rui
R
Hu
Yong
Y
Jiang
Xiqun
X
Guo
Wanhua
W
Liu
Baorui
B
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002945:Cisplatin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D006801:Humans; D015552:Injections, Intralesional; D007274:Injections, Intraperitoneal; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D049268:Positron-Emission Tomography; D012995:Solubility; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D011092:Polyethylene Glycols; D002945:Cisplatin