Characterization and cellular uptake of platinum anticancer drugs encapsulated in apoferritin.
Clinical application of platinum-based anticancer drugs is largely limited by severe general toxicity and drug resistance. Drug delivery systems with tumor-targeting potential are highly desired for improving the efficacy and applicability of these drugs. This study describes an alternative strategy for the delivery of platinum drugs (cisplatin, carboplatin and oxaliplatin) by encapsulating each of them in the cavity of apoferritin (AFt). The encapsulation was achieved through manipulating the pH-dependent unfolding-refolding process of AFt at pH 2.0 and 7.4, respectively, in saturated drug solution. UV-vis spectrometry, circular dichroism spectrometry, dynamic light scattering, and inductively coupled plasma mass spectrometry were used to characterize the AFt-drug complexes. The loading capacity of AFt varies with respective drugs and the structural integrity of the protein shell remains intact after encapsulation. In vitro assays on the rat pheochromocytoma cell line (PC12) show that AFt-cisplatin inhibits the cells in a slow but sustaining mode and the cellular uptake of platinum is enhanced by AFt. AFt-carboplatin and AFt-oxaliplatin complexes only exhibit a marginal cytotoxicity towards this cell line under similar concentrations.
Xing
Ruimin
R
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, PR China.
Wang
Xiaoyong
X
Zhang
Changli
C
Zhang
Yangmiao
Y
Wang
Qi
Q
Yang
Zhen
Z
Guo
Zijian
Z
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001052:Apoferritins / Q000008:administration & dosage* / Q000737:chemistry; D016190:Carboplatin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000077150:Oxaliplatin; D051381:Rats
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D001052:Apoferritins; D016190:Carboplatin; D002945:Cisplatin