RESUMO
As one of the leading and most important metal-based drugs, platinum-based pharmaceuticals are widely used in the treatment of solid malignancies. Despite significant side effects and acquired drug resistance have limited their clinical applications, platinum has shown strong inhibitory effects for a wide assortment of tumors. Drug delivery systems using emerging technologies such as liposomes, dendrimers, polymers, nanotubes and other nanocompositions, all show promise for the safe delivery of platinum-based compounds. Due to the specificity of nano-formulations; unwanted side-effects and drug resistance can be largely averted. In addition, combinational therapy has been shown to be an effective way to improve the efficacy of platinum based anti-tumor drugs. This review first introduces drug delivery systems used for platinum and combinational therapeutic delivery. Then we highlight some of the recent advances in the field of drug delivery for combinational therapy; specifically progress in leveraging the cytotoxic nature of platinum-based drugs, the combinational effect of other drugs with platinum, while evaluating the drug targeting, side effect reducing and sitespecific nature of nanotechnology-based delivery platforms.
Assuntos
Sistemas de Liberação de Medicamentos , Antineoplásicos , Humanos , Neoplasias , Platina , Compostos de PlatinaRESUMO
Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a well-characterized tumour-suppressor gene that is lost or mutated in about half of metastatic castration-resistant prostate cancers and in many other human cancers. The restoration of functional PTEN as a treatment for prostate cancer has, however, proven difficult. Here, we show that PTEN messenger RNA (mRNA) can be reintroduced into PTEN-null prostate cancer cells in vitro and in vivo via its encapsulation in polymer-lipid hybrid nanoparticles coated with a polyethylene glycol shell. The nanoparticles are stable in serum, elicit low toxicity and enable high PTEN mRNA transfection in prostate cancer cells. Moreover, significant inhibition of tumour growth is achieved when delivered systemically in multiple mouse models of prostate cancer. We also show that the restoration of PTEN function in PTEN-null prostate cancer cells inhibits the phosphatidylinositol 3-kinase (PI3K)-AKT pathway and enhances apoptosis. Our findings provide proof-of-principle evidence of the restoration of mRNA-based tumour suppression in vivo.
Assuntos
Nanopartículas/química , PTEN Fosfo-Hidrolase/genética , RNA Mensageiro/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Lipídeos/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , PTEN Fosfo-Hidrolase/deficiência , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Polietilenoglicóis/química , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/química , Transdução de Sinais , Distribuição Tecidual , Transfecção/métodosRESUMO
The authors wish to add the following sentence into the 'Competing interests' section of this Article: "P.W.K. has investment interest in Context Therapeutics LLC, DRGT, Placon, Seer Biosciences and Tarveda Therapeutics, is a company board member for Context Therapeutics LLC, is a consultant and scientific advisory board member for BIND Biosciences, Inc., BN Immunotherapeutics, DRGT, GE Healthcare, Janssen, Metamark, New England Research Institutes, Inc., OncoCellMDX, Progenity, Sanofi, Seer Biosciences, Tarveda Therapeutics and Thermo Fisher, and serves on data safety monitoring boards for Genentech/Roche and Merck." This has now been included.