Ratiometric delivery of cisplatin and doxorubicin using tumour-targeting carbon-nanotubes entrapping platinum(<scp>iv</scp>) prodrugs

Chin, Chee Fei; Yap, Siew Qi; Li, Jian; Pastorin, Giorgia; Ang, Wee Han

doi:10.1039/c3sc53106f

Cited by 70 publications

(52 citation statements)

References 51 publications

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“…A prodrug was designed that is capable of releasing one equivalent of doxorubicin for every equivalent of cisplatin released (Chart 18). 424 This feat was achieved by forming an amide bond between the amine group of doxorubicin and the succinate of cis,cis,trans -[Pt(NH 3 ) 2 Cl 2 (O 2 CC 6 H 5 )(O 2 CCH 2 CH 2 CO 2 H)]. The final complex is sufficiently hydrophobic to be encapsulated within the nanotubes and importantly releases the two chemotherapeutic agents at relative concentrations close to those administered during combination chemotherapy.…”

Section: Nanodelivery Of Platinum(iv) Complexesmentioning

confidence: 99%

The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs

2016

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The platinum drugs, cisplatin, carboplatin, and oxaliplatin, prevail in the treatment of cancer,, but new platinum agents have been very slow to enter the clinic. Recently, however, there has been a surge of activity, based on a great deal of mechanistic information, aimed at developing non-classical platinum complexes that operate via mechanisms of action distinct from those of the approved drugs. The use of nanodelivery devices has also grown and many different strategies have been explored to incorporate platinum warheads into nanomedicine constructs. In this review, we discuss these efforts to create the next generation of platinum anticancer drugs. The introduction provides the reader with a brief overview of the use, development, and mechanism of action of the approved platinum drugs to provide the context in which more recent research has flourished. We then describe approaches that explore non-classical platinum(II) complexes with trans geometry and with a monofunctional coordination mode, polynuclear platinum(II) compounds, platinum(IV) prodrugs, dual-treat agents, and photoactivatable platinum(IV) complexes. Nanodelivery particles designed to deliver platinum(IV) complexes will also be discussed, including carbon nanotubes, carbon nanoparticles, gold nanoparticles, quantum dots, upconversion nanoparticles, and polymeric micelles. Additional nanoformulations including supramolecular self-assembled structures, proteins, peptides, metal-organic frameworks, and coordination polymers will then be described. Finally, the significant clinical progress made by nanoparticle formulations of platinum(II) agents will be reviewed. We anticipate that such a synthesis of disparate research efforts will not only help to generate new drug development ideas and strategies, but also reflect our optimism that the next generation of platinum cancer drugs is about to arrive.

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Section: Nanodelivery Of Platinum(iv) Complexesmentioning

confidence: 99%

The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs

2016

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“…Once Pt (IV) complex coupled to nanocarriers, the complexes could be specifically delivered to the tumor site, with improved stability in blood, minimized off‐target distribution, and controlled payload release. Additionally, the nanocarrier could protect Pt (IV) complex from binding with plasma proteins and prereduction in the blood circulation . In general, Pt (IV) complexes were coupled to nanocarriers via two methods: covalent conjugation and physical encapsulation.…”

Section: Platinum (Iv) Complex‐based Delivery Systemsmentioning

confidence: 99%

“…Additionally, the nanocarrier could protect Pt (IV) complex from binding with plasma proteins and prereduction in the blood circulation. 127,128 In general, Pt (IV) complexes were coupled to nanocarriers via two methods: covalent conjugation and physical encapsulation. Physical encapsulation was one of the common methods to load the hydrophobic drugs within nanocarriers.…”

Section: Pt (Iv) Complexes Coupled To Nanocarriersmentioning

confidence: 99%

Recent Advances in Platinum (IV) Complex‐Based Delivery Systems to Improve Platinum (II) Anticancer Therapy

Han

Sun

Wang

et al. 2015

Medicinal Research Reviews

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Cisplatin and its platinum (Pt) (II) derivatives play a key role in the fight against various human cancers such as testicular, ovarian, head and neck, lung tumors. However, their application in clinic is limited due to dose- dependent toxicities and acquired drug resistances, which have prompted extensive research effort toward the development of more effective Pt (II) delivery strategies. The synthesis of Pt (IV) complex is one such an area of intense research fields, which involves their in vivo conversion into active Pt (II) molecules under the reducing intracellular environment, and has demonstrated encouraging preclinical and clinical outcomes. Compared with Pt (II) complexes, Pt (IV) complexes not only exhibit an increased stability and reduced side effects, but also facilitate the intravenous-to-oral switch in cancer chemotherapy. The overview briefly analyzes statuses of Pt (II) complex that are in clinical use, and then focuses on the development of Pt (IV) complexes. Finally, recent advances in Pt (IV) complexes in combination with nanocarriers are highlighted, addressing the shortcomings of Pt (IV) complexes, such as their instability in blood and irreversibly binding to plasma proteins and nonspecific distribution, and taking advantage of passive and active targeting effect to improve Pt (II) anticancer therapy.

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“…Collectively we infer that the presence of linkers between MWCNTs and HKII( pep) does not impact the peptide's bioactivity. 39 To ascertain that the cytotoxicity observed with HKII( pep) conjugated MWCNT constructs was due to the activity of HKII-( pep) rather than the intrinsic toxicity of MWCNTs, we performed the WST-1 assay on cells exposed to the empty carrier (Fig. We reason that as HKII( pep) contains fifteen amino acids, the presence of a mere 6-carbon TEG linker might be insignificant in decreasing steric hindrance.…”

Section: Cytotoxicity Assay Of Hkii( Pep)-functionalized Mwcntsmentioning

confidence: 99%

Mitochondria-acting hexokinase II peptides carried by short-length carbon nanotubes with increased cellular uptake, endosomal evasion, and enhanced bioactivity against cancer cells

et al. 2015

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Type II hexokinase (HKII) has emerged as a viable therapeutic target due to its involvement in metabolic reprogramming and also apoptosis prevention. The peptide derived from the fifteen amino acid sequence in the HKII N-terminal region [HKII(pep)] can compete with endogenous proteins for binding on mitochondria and trigger apoptosis. However, this peptide is not cell-permeable. In this study, multi-walled carbon nanotubes (MWCNTs) were used to effectively deliver HKII(pep) across cellular barriers without compromising their bioactivity. The peptide was conjugated on either oxidized MWCNTs or 2,2'-(ethylenedioxy)bis(ethylamine)-functionalized MWCNTs, yielding MWCNT-HKII(pep) and MWCNT-TEG-HKII(pep), respectively. Both conjugates were shown to be internalized by breast cancer MCF-7 cells using confocal microscopy. Moreover, these nanoconjugates seemed to have escaped from endosomes and be in the vicinity of mitochondria. The WST-1 cytotoxicity assay conducted on MCF-7 and colon carcinoma HCT116 cells revealed that MWCNT-peptide conjugates were significantly more effective in curbing cancer cell growth compared to a commercially available cell permeable HKII fusion peptide. In addition, both nanoconjugates displayed an enhanced ability in eliciting apoptosis and depleting the ATP level in HCT116 cells compared to the mere HKII peptide. Importantly, hexokinase II release from mitochondria was demonstrated in MWCNT-HKII(pep) and MWCNT-TEG-HKII(pep) treated cells, highlighting that the structure and bioactivity of HKII(pep) were not compromised after covalent conjugation to MWCNTs.

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Ratiometric delivery of cisplatin and doxorubicin using tumour-targeting carbon-nanotubes entrapping platinum(iv) prodrugs

Abstract: A hydrophobic platinum(iv) prodrug was entrapped in tumour-targeting multiwalled carbon nanotubes for synchronous and ratiometric delivery of drug combinations.

Cited by 70 publications

References 51 publications

The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs

The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs

Recent Advances in Platinum (IV) Complex‐Based Delivery Systems to Improve Platinum (II) Anticancer Therapy

Mitochondria-acting hexokinase II peptides carried by short-length carbon nanotubes with increased cellular uptake, endosomal evasion, and enhanced bioactivity against cancer cells

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