A Polymer–(Tandem Drugs) Conjugate for Enhanced Cancer Treatment

Zhou, Dongfang; Xiao, Haihua; Meng, F.; Li, Xiaoyuan; Li, Yuxin; Jing, Xiabin; Huang, Yubin

doi:10.1002/adhm.201200385

Cited by 48 publications

(39 citation statements)

References 37 publications

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“…Recently, demethylcantharidin (DMC), as protein phosphatase 2A (PP2A) inhibitor, showed enhanced antitumor activity with DNA‐damaging agents by specifically inhibition of PP2A without evident acute or chronic toxicity . Previous studies have shown that combination use of cisplatin and DMC could synergize cancer therapy …”

Section: Methodsmentioning

confidence: 99%

“…The key features in DDBSP and DD‐NP include: (i) Dual synergistic drugs were combined at a fixed and precise ratio in DD‐NP for precise nanomedicine with extraordinary high drug loading that can hardly be achieved in other delivery systems via conventional drug conjugation/encapsulation. (ii) The backbone‐type polymer was site‐specifically chain‐shattered via reduction of Pt(IV) to Pt(II) and acidolysis of DMC‐containing β‐carboxylic amide to DMC in the endosomal/lysosomal reductive and acidic microenvironments, making the drug release in a controlled but triggered manner . (iii) The exceptional high content of Pt heavy metals in the polymer chain assures possible monitoring of the spatial/temporal dynamic distribution as well as metabolism of NPs via Pt‐based drug‐mediated computer tomography (DMCT).…”

Section: Methodsmentioning

confidence: 99%

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Dual Drug Backboned Shattering Polymeric Theranostic Nanomedicine for Synergistic Eradication of Patient‐Derived Lung Cancer

et al. 2018

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Most of the current nanoparticle-based therapeutics worldwide failing in clinical trials face three major challenges: (i) lack of an optimum drug delivery platform with precise composition, (ii) lack of a method of directly monitoring the fate of a specific drug rather than using any other labelling molecules as a compromise, and (iii) lack of reliable cancer models with high fidelity for drug screen and evaluation. Here, starting from a PP2A inhibitor demethylcantharidin (DMC) and cisplatin, the design of a dual sensitive dual drug backboned shattering polymer (DDBSP) with exact composition at a fixed DMC/Pt ratio for precise nanomedicine is shown. DDBSP self-assembled nanoparticle (DD-NP) can be triggered intracellularly to break down in a chain-shattering manner to release the dual drugs payload. Moreover, DD-NP with extremely high Pt heavy metal content in the polymer chain can directly track the drug itself via Pt-based drug-mediated computer tomography and ICP-MS both in vitro and in vivo. Finally, DD-NP is used to eradicate the tumor burden on a high-fidelity patient-derived lung cancer model for the first time.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Dual Drug Backboned Shattering Polymeric Theranostic Nanomedicine for Synergistic Eradication of Patient‐Derived Lung Cancer

et al. 2018

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Section: Platinum (Iv) Complex‐based Delivery Systemsmentioning

confidence: 99%

“…Compared to cisplatin, Pt (IV) complexes are more inert, but there are still some limitations, such as instability in blood, rapid removal by kidney, and wide distribution in normal tissues. 125,126 It is desired that most of Pt (IV) complexes are reduced to Pt (II) complexes within tumor cells. However, once Pt (IV) complexes entered the blood, most of them were irreversibly bound to plasma proteins and the effective therapeutical dosage was reduced.…”

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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“…93 The nano-sized conjugate exhibited superior activity and safety over the free drugs in mice bearing orthotopic mammary adenocarcinomas. An interesting example of this strategy is provided by Zhou et al 94 Rather than conjugating the two drugs—cisplatin (CIS) and demethylcantharidin (DMC)—to individual sites on the polymer chain, they took advantage of the redox activity of Pt to oxidise the four-coordinate Pt(II) to six-coordinate Pt(IV) and then complex it with DMC. This tandem drug complex, Z-DMC-CIS, was then conjugated to a PEG- b -P(LA- co -MCC/OH) copolymer via the DMC’s second carboxylate group, creating a PDC that assembled through nanoprecipitation into micelles 200–240 nm in diameter.…”

Section: Macromolecular Sapdsmentioning

confidence: 99%

Self-assembling prodrugs

et al. 2017

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Covalent modification of therapeutic compounds is a clinically proven strategy to devise prodrugs with enhanced treatment efficacies. This prodrug strategy relies on modified drugs that possess advantageous pharmacokinetic properties and administration routes over their parent drug. Self-assembling prodrugs represent an emerging class of therapeutic agents capable of spontaneously associating into well-defined supramolecular nanostructures in aqueous solutions. The self-assembly of prodrugs expands the functional space of conventional prodrug design, providing a possible pathway to more effective therapies as the assembled nanostructure possesses distinct physicochemical properties that can be tailored to specific administration routes and disease treatment. In this review, we will discuss the various types of self-assembling prodrugs in development, providing an overview of the methods used to control their structure and function and, ultimately, our perspective on their current and future potential.

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A Polymer–(Tandem Drugs) Conjugate for Enhanced Cancer Treatment

Cited by 48 publications

References 37 publications

Dual Drug Backboned Shattering Polymeric Theranostic Nanomedicine for Synergistic Eradication of Patient‐Derived Lung Cancer

Dual Drug Backboned Shattering Polymeric Theranostic Nanomedicine for Synergistic Eradication of Patient‐Derived Lung Cancer

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

Self-assembling prodrugs

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