125074-46-6

Upstream product

• 26035-31-4 cisplatine 
• 7722-84-1 dihydrogen peroxide 
• 15663-27-1 cisplatin 
• 7732-18-5 water 
• 26035-31-4 transplatin 
• 7722-64-7 potassium permanganate 

Downstream Products

• 16893-05-3 cis-diaammineplatinum(IV) tetrachloride 
• 15663-27-1 cisplatin 

Relevant academic research and scientific papers

Chlorambucil-conjugated platinum(IV) prodrugs to treat triple-negative breast cancer in vitro and in vivo

Modification of platinum (II) into lipophilic platinum (IV) compounds by introducing biologically active molecules were widely employed to develop new platinum-based prodrugs in the past decade. In this paper, two chlorambucil platinum (IV) complexes, CLB-Pt and CLB-Pt-CLB, were synthesized and displayed very potent antiproliferative activity against all the tested cancer cell lines, such as A549, HeLa and MCF-7, especially to treat the well-known refractory triple-negative breast cancer. CLB-Pt-CLB significantly improved cell-killing effect in triple-negative subtype MDA-MB-231 cells, and showed much stronger cytotoxicity than either monotherapy or combination of cisplatin and chlorambucil. CLB-Pt-CLB prodrug entered cells in dramatically increased amount compared with cisplatin and enhanced DNA damage, inducing cancer cell apoptosis. It exhibited high anticancer activity and no observable toxicity in BALB/c nude mice bearing MDA-MB-231 tumors. The chlorambucil moiety not only greatly assisted the passive diffusion of CLB-Pt-CLB into cells, but also produced the synergism with cisplatin in targeting DNA.

Mesoporous NaYF4:Yb,Er@Au-Pt(iv)-FA nanospheres for dual-modal imaging and synergistic photothermal/chemo-anti-cancer therapy

In this report, mesoporous NaYF4:Yb,Er@Au-Pt(iv)-FA up-conversion nanoparticles (UCNPs) have been designed by attaching Au NPs and Pt(iv) pro-drugs on the surface of PEI hydrogel modified mesoporous NaYF4:Yb,Er nanospheres. Finally the molecules modified with folic acid (FA) improve the receptor-mediated endocytosis. Because of the doped rare earth ions in the host matrix, the as-synthesized platform exhibits excellent up-conversion luminescence (UCL) imaging and computed X-ray tomography (CT) imaging properties. Diverse methods including MTT assay, hemolysis experiments, and live/dead cell analysis were employed to evaluate the biocompatibility and ablation efficacy of the as-synthesized platform. It was found that the cytotoxicity of the platform can be tuned by eliminating the axial ligands reductively during intracellular endocytosis. Especially, under 980 nm near-infrared (NIR) irradiation, the platform shows excellent inhibition toward cancer cells due to the synergistic photothermal injury to enzymes and membrane integrity combined with the DNA binding of activated Pt(ii) to avoid cell proliferation. The developed nanocomposite may thus be a promising imaging-guided synergistic anti-cancer platform.

Synthesis and characterization of hyaluronic acid-platinum(IV) nanoconjugate with enhanced antitumor response and reduced adverse effects

A hyaluronic acid-platinum(iv) nanoconjugate with a high drug loading capacity was developed to mitigate the side effects of platinum(ii). Pt(iv), HA-EDA, and HA-EDA-Pt(iv) nanoconjugates were investigated by 1H NMR, 13C NMR, FT-NIR, and DSC. Negatively charged polymer-drug conjugates were of a uniform size around 186.4 nm and spherical in shape. In vitro antiproliferation and in vivo apoptosis assays proved that the nanomedicine possessed high cytotoxicity towards cancer cells. The enhanced antitumor effect was attributed to HA receptor-mediated endocytosis. Nanoscale conjugates exhibited desirable blood compatibility and negligible stimulation to blood vessels. The systemic toxicity study showed that polymer-drug conjugates were much safer than the parent drug evidenced by biochemical and histological analyses. The concise design of the nanoconjugate offers a simple way to overcome the toxicity and non-selectivity of cisplatin, which could improve therapeutical outcomes of platinum drugs in cancer therapy.

Impact of Mitochondrion-Targeting Group on the Reactivity and Cytostatic Pathway of Platinum(IV) Complexes

Platinum(IV) complexes are prodrugs of cisplatin with multiple potential advantages over platinum(II) drugs. Mitochondria play pivotal roles in producing energy and inducing death of cancer cells. Two platinum(IV) complexes, namely, c,c,t-[Pt(NH3)2Cl2(OH)(OCOCH2CH2CH2CH2PPh3)]Br and c,c,t-[Pt(NH3)2Cl2(OCOCH2CH2CH2CH2PPh3)2]Br2, were designed to explore the effect of mitochondrion-targeting group(s) on the bioactivity and cytotoxicity of platinum(IV) complexes. The complexes were characterized by electrospray ionization mass spectrometry, reverse-phase high-performance liquid chromatography, and multinuclear (1H, 13C, 31P, and 195Pt) NMR spectroscopy. The introduction of triphenylphosphonium targeting group(s) markedly influences the reactivity and cytotoxicity of the Pt(IV) complexes. The targeted complex displays more potent disruptive effect on mitochondria but less inhibitory effect on cancer cells than cisplatin. The lipophilicity of the Pt(IV) complexes is enhanced by the targeting group(s), while their reactivity to DNA is decreased. As a result, the mitochondrial morphology and adenosine triphosphate producing ability are impaired, which constitutes an alternative pathway to inhibit cancer cells. This study shows that both the reactivity of platinum(IV) center and the property of axial targeting ligand exert influences on the cytotoxicity of targeted Pt(IV) complexes. For targeting groups with pharmacological activities, their intrinsic function could enrich the anticancer mechanism of Pt(IV) complexes.

The dual-role of Pt(iv) complexes as active drug and crosslinker for micelles based on β-cyclodextrin grafted polymer

With a combination of RAFT and click chemistry an amphiphilic block copolymer with poly(ethylene glycol) methyl ether methacrylate (POEGMEMA) as hydrophilic block and poly(propargyl methacrylate) (PMA) as hydrophobic block has been successfully synthesized. To this, 6-azide-6-deoxy-β-cyclodextrin (N3-β-CD) was clicked creating a hosting environment for a hydrophobic small molecule platinum pro-drug. Oxoplatin, the oxidized version of cisplatin, has been modified on its axial ligand introducing cholic acid groups through esterification. This modified cisplatin forms a host-guest complex with β-cyclodextrin that has been characterised via NMR spectroscopy. The host-guest interaction that the drug established with the β-cyclodextrin grafted copolymer drove the self-assembly into nanoparticles of a diameter of 266 nm able to physical encapsulate the platinum-based drug. In the presence of ascorbic acid, 70% of the pro-drug is released over a period of 24 h. Cytotoxicity assays on ovarian cancer cells show that the polymer carrier improves the cytotoxicity of the platinum pro-drug. The IC50 value decreases from 37.7 μM with the pro-drug to 20.4 μM when the pro-drug is encapsulated into the polymer carrier. This is due to the fact that the uptake of the polymer carrier is up to 6 fold higher than the significantly smaller pro-drug by itself.

Supramolecular self-assembled nanoparticles for chemo-photodynamic dual therapy against cisplatin resistant cancer cells

Supramolecular self-assembled nanoparticles that can overcome cisplatin resistance were constructed by utilizing a platinum(iv) prodrug bridged β-cyclodextrin dimer and adamantyl group modified porphyrin as the host and guest molecules, respectively.

DNA Nanostructures as Pt(IV) Prodrug Delivery Systems to Combat Chemoresistance

Cisplatin is a first-line drug in clinical cancer treatment but its efficacy is often hindered by chemoresistance in cancer cells. Reduced intracellular drug accumulation is revealed to be a major mechanism of cisplatin resistance. Nanoscale drug delivery systems could help to overcome this problem because of their more active cellular uptake and more accurate tumor localization. DNA nanostructures have emerged as promising drug delivery systems because of their intrinsic biocompatibility and structural programmability. Herein, three diverse DNA nanostructures are constructed and their potential for cisplatin prodrug delivery is investigated. Results found that these DNA nanostructures could remarkably enhance the cellular internalization of platinum drugs and thus increase the anticancer activity, not only to regular lung cancer cells (A549), but more importantly to cisplatin-resistant cancer cells (A549cisR). Further, in vivo studies also demonstrate that cisplatin prodrug loaded DNA nanostructures could effectively suppress tumor growth in both regular and cisplatin-resistant tumor models. This study suggests that DNA nanostructures are effective carriers for platinum prodrug delivery to combat chemoresistance.

Naphthalimide Platinum(IV) Compounds as Antitumor Agents with Dual DNA Damage Mechanism to Overcome Cisplatin Resistance

A new series of naphthalimide platinum(IV) compounds with dual DNA damage mechanism were designed, synthesized and evaluated for antitumor activities. The platinum(IV) compounds could combine with DNA and cause DNA damage via naphthalimide fragment. Then the platinum(II) complexes released in reductive microenvironment would cause remarkable secondary DNA lesions. Some title compounds exhibit good antitumor activities and are of great potential in overcoming the drug resistance of cisplatin. Furthermore, naphthalimide platinum(IV) complexes could effectively combine with HSA by electrostatic force, which would influence the drug distribution and bioactivities in vivo. Moreover, the accumulation of the tested platinum(IV) compounds in whole cells and DNA is remarkably enhanced in comparison with cisplatin and oxaliplatin.

Multispecific Platinum(IV) Complex Deters Breast Cancer via Interposing Inflammation and Immunosuppression as an Inhibitor of COX-2 and PD-L1

Breast cancer (BC) is one of the most common malignancies in women and often accompanied by inflammatory processes. Cyclooxygenase-2 (COX-2) plays a vital role in the progression of BC, correlating with the expression of programmed death-ligand 1 (PD-L1). Overexpression of PD-L1 contributes to the immune escape of cancer cells, and its blockade would stimulate anticancer immunity. Two multispecific platinum(IV) complexes DNP and NP were prepared using non-steroidal antiinflammatory drug naproxen (NPX) as axial ligand(s) to inhibit the BC cells. DNP exhibited high cytotoxicity and antiinflammatory properties superior over NP, cisplatin and NPX; moreover, it displayed potent antitumor activity and almost no general toxicity in mice bearing triple-negative breast cancer (TNBC). Mechanistic studies revealed that DNP could downregulate the expression of COX-2 and PD-L1 in vitro and vivo, inhibit the secretion of prostaglandin, reduce the expression of BC-associated protein BRD4 and phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2), and block the oncogene c-Myc in BC cells. These findings demonstrate that DNP is capable of intervening in inflammatory, immune, and metastatic processes of BC, thus presenting a new mechanism of action for anticancer platinum(IV) complexes. The multispecificity offers a special superiority for DNP to treat TNBC by combining chemotherapy and immunotherapy in one molecule.

Synthesis and evaluation of bi-functional 7-hydroxycoumarin platinum(IV) complexes as antitumor agents

A series of bi-functional 7-hydroxycoumarin platinum(IV) complexes were synthesized, characterized, and evaluated for antitumor activities. The 7-hydroxycoumarin platinum(IV) complexes display moderate to effective antitumor activities toward the tested cell lines and show much potential in overcoming drug resistance of platinum(II) drugs. In reducing microenvironment, the title compounds could be reduced to platinum(II) complex accompanied with two equivalents of coumarin units. By a unique mechanism, the 7-hydroxycoumarin platinum(IV) complex attacks DNA via the released platinum(II) compound, meanwhile it also inhibits the activities of cyclooxygenase by coumarin fragment. This action mechanism might be of much benefit for reducing tumor-related inflammation in the progress of inhibiting tumor proliferation and overcoming cisplatin resistance. The incorporation of 7-hydroxycoumarin leads to significantly enhanced platinum accumulation in both whole tumor cells and DNA. The HSA interaction investigation reveals that the tested coumarin platinum(IV) compound could effectively combine with HSA via van der Waals force and hydrogen bond.