| Cancer has already seriously threatened human health and lives. The existing three cancer treatments approaches, including surgery, radiotherapy, chemical treatment. In the chemical treatment, platinum drugs are very important. But because of its disadvantage of diffusion distribution in vivo, rapid metabolic elimination and side effects seriously restrict platinum drugs further development. Recently, polymer platinum drug conjugate was conceived which canprotect the drug before it arrive destination, improve the stability of drugs, prolong the blood circulation and reduce the toxicity.So which have gained extensive attention.This dissertation designes and synthesizes a photosensitive platinum(IV) prodrug(UVA-Pt2)andabiodegradablepolymer(methoxyl-poly(ethyleneglycol)-block-poly(lactide-co-2-methyl-2-carboxyl-propylene carbonate-ethanol amine),PE) and thereafter attaching UVA-Pt2 to PE. Then the conjugate was self-assembled to micelles(NP-UVA-Pt2). UV-vis,drug release,MALDI-TOF-MS studies the product of light release,which illustrates the mechanism of drug release. MTT assay of NP-UVA-Pt2 demonstrated an improved cytotoxicity against SKOV-3 cells than that of cisplatin. Confocal laser scanning microscopy(CLSM) indicated that NP-UVA-Pt2 were endocytosed rather than internalized by passive diffusion, and thus, this process has nothing to do with copper transporter protein(Ctr1) as reported for cisplatin, which is closely related to drug resistance of Pt based drugs. Intracellular platinum content measured by ICP-MS result suggested that NP-UVA-Pt2 expressed higher platinum intracellular uptake than cisplatin. NP-UVA-Pt2 demonstrated fastand robust response to photo irradiation while the nanoparticles were very stable in the dark. The great drug efficacy of NP-UVA-Pt2 under UVA irradiation and the ineffectiveness in the dark makes NP-UVA-Pt2 an ideal light responsive on-demand drug delivery system. Hence, NP-UVA-Pt2 will be a promising platinum based drug in the near future. |
PDF Full Text Request