A novel nanoassembled doxorubicin prodrug with a high drug loading for anticancer drug delivery

Xu, Zhigang; Zhang, Kelin; Hou, Chunmei; Wang, Dongdong; Liu, Xiaoyan; Guan, Xiao; Zhang, Xiaoyu; Zhang, Haixia

doi:10.1039/c4tb00128a

Cited by 43 publications

(35 citation statements)

References 38 publications

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“…As such, we further determined the intercalating efficacy to enable us to compare our DNA TH effectiveness as a cancer drug carrier with other current nanomedicine formulations available. Our result indicated that our DOX intercalating efficacy (or also known as loading efficiency) on the DNA TH was ≈79 wt%, which is slightly higher than the polyethylene glycol based (80 nm) nanomedicine's DOX loading efficiency of 67 wt% . However, our DNA TH showed far superior loading efficiency when compared to many other nanomedicine formulations of the same size.…”

Section: Resultsmentioning

confidence: 67%

DNA Nanostructures Carrying Stoichiometrically Definable Antibodies

Setyawati

Kutty

Leong

2016

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105

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Targeted drug delivery is one of the key challenges in cancer nanomedicine. Stoichiometric and spatial control over the antibodies placement on the nanomedicine vehicle holds a pivotal role to overcome this key challenge. Here, a DNA tetrahedral is designed with available conjugation sites on its vertices, allowing to bind one, two, or three cetuximab antibodies per DNA nanostructure. This stoichiometrically definable cetuximab conjugated DNA nanostructure shows enhanced targeting on the breast cancer cells, which results with higher overall killing efficacy of the cancer cells.

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Section: Resultsmentioning

confidence: 67%

DNA Nanostructures Carrying Stoichiometrically Definable Antibodies

Setyawati

Kutty

Leong

2016

Small

105

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“…Xu et al reported a novel graft polymer-Dox conjugate with a Dox-loading content as high as 40 wt%, namely, PEG monomethylether-b-poly(methacrylamide tert-butyl carbazate-Dox) (MPEG-b-Dox) ( Figure 6). 156 The MPEG in this conjugate functioned as the hydrophilic part, and methacrylamide tert-butyl carbazate, which was conjugated to Dox via an acid-labile hydrazine bond, acted as the hydrophobic part. The amphiphilic conjugates selfassembled into micelles with average hydrodynamic size of 80 nm.…”

mentioning

confidence: 99%

High drug-loading nanomedicines: progress, current status, and prospects

Shen

Liu

et al. 2017

IJN

438

268

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Drug molecules transformed into nanoparticles or endowed with nanostructures with or without the aid of carrier materials are referred to as “nanomedicines” and can overcome some inherent drawbacks of free drugs, such as poor water solubility, high drug dosage, and short drug half-life in vivo. However, most of the existing nanomedicines possess the drawback of low drug-loading (generally less than 10%) associated with more carrier materials. For intravenous administration, the extensive use of carrier materials might cause systemic toxicity and impose an extra burden of degradation, metabolism, and excretion of the materials for patients. Therefore, on the premise of guaranteeing therapeutic effect and function, reducing or avoiding the use of carrier materials is a promising alternative approach to solve these problems. Recently, high drug-loading nanomedicines, which have a drug-loading content higher than 10%, are attracting increasing interest. According to the fabrication strategies of nanomedicines, high drug-loading nanomedicines are divided into four main classes: nanomedicines with inert porous material as carrier, nanomedicines with drug as part of carrier, carrier-free nanomedicines, and nanomedicines following niche and complex strategies. To date, most of the existing high drug-loading nanomedicines belong to the first class, and few research studies have focused on other classes. In this review, we investigate the research status of high drug-loading nanomedicines and discuss the features of their fabrication strategies and optimum proposal in detail. We also point out deficiencies and developing direction of high drug-loading nanomedicines. We envision that high drug-loading nanomedicines will occupy an important position in the field of drug-delivery systems, and hope that novel perspectives will be proposed for the development of high drug-loading nanomedicines.

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“…However, the number of researchers exploring this area and developing new approaches has greatly expanded over the last six years as the field of nanomedicine gathered momentum. For instance, Zhong, 55 Zhang, 56 and Xie 57 took advantage of improvements in polymer synthesis to construct their respective self-assembling PDCs. Both the Zhong and Zhang groups utilized reversible addition-fragmentation chain-transfer (RAFT) polymerization to produce polymer backbones with low polydispersity and controlled molecular weight.…”

Section: Macromolecular Sapdsmentioning

confidence: 99%

“…Zhang, on the other hand, synthesized a hydrazide-bearing monomer forming the polymer MPEG-MBAH 6 (methacrylamide Boc-hydrazide). 56 Removal of the Boc protecting group then enabled DOX incorporation through hydrazone formation (Figure 4b). Xie and co-workers used anionic ring opening polymerization (ROP) to create a vinyl-functionalized polymer, PEG- b -PAGE (poly(allyl glycidyl ether)), which was then converted to a carboxylate-bearing polymer for the attachment of PTX (Figure 4c).…”

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 novel nanoassembled doxorubicin prodrug with a high drug loading for anticancer drug delivery

Abstract: A novel doxorubicin (DOX) prodrug (MPEG-b-DOX) was synthesized that reduces the proportion of inactive materials and minimizes drug leak.

Cited by 43 publications

References 38 publications

DNA Nanostructures Carrying Stoichiometrically Definable Antibodies

DNA Nanostructures Carrying Stoichiometrically Definable Antibodies

High drug-loading nanomedicines: progress, current status, and prospects

Self-assembling prodrugs

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