Prodrugs Forming High Drug Loading Multifunctional Nanocapsules for Intracellular Cancer Drug Delivery

Shen, Youqing; Jin, Erlei; Zhang, Bo; Murphy, Caitlin J.; Sui, Meihua; Zhao, Jian; Wang, Jinqiang; Tang, Jianbin; Fan, Maohong; Kirk, Edward Van; Murdoch, William J.

doi:10.1021/ja909475m

Cited by 544 publications

(369 citation statements)

References 76 publications

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“…As reported previously, combined use of a small molecule drugs and genes with vectors, including liposomes, polymeric micelles, and inorganic nanoparticles, is a promising approach for disease therapy. However, the drug‐loading of these vectors has been low, not greater than 10%,30 thereby discounting therapeutic outcomes. Here, the drug‐loading in CNPs reached up to 500%, and thus this combined strategy has the potential to overcome this limitation of commonly utilized vectors.…”

Section: Discussionmentioning

confidence: 99%

Rod‐Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery

et al. 2017

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Efficient microRNAs (miRNA) delivery into cells is a promising strategy for disease therapy, but is a major challenge because the available conventional nonviral vectors have significant drawbacks. In particular, after these vectors are entrapped in lysosomes, the escape efficiency of genes from lysosomes into the cytosol is less than 2%. Here, a novel approach for lethal‐7a (let‐7a) replacement therapy using rod‐shaped active pure drug nanoparticles (≈130 nm in length, PNPs) with a dramatically high drug‐loading of ≈300% as vectors is reported. Importantly, unlike other vectors, the developed PNPs/let‐7a complexes (≈178 nm, CNPs) can enter cells and bypass the lysosomal route to localize to the cytosol, achieving efficient intracellular delivery of let‐7a and a 50% reduction in expression of the target protein (KRAS). Also, CNPs prolong the t 1/2 of blood circulation by ≈threefold and increase tumor accumulation by ≈1.5–2‐fold, resulting in significantly improved antitumor efficacies. Additionally, no damage to normal organs is observed following systemic injection of CNPs. In conclusion, rod‐shaped active PNPs enable efficient and safe delivery of miRNA with synergistic treatment for disease. This nanoplatform would also offer a viable strategy for the potent delivery of proteins and peptides in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Rod‐Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery

et al. 2017

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“…To surmount these limitations, Shen, et al used hydrophobic drugs as a hydrophobic part of the block copolymer or nanoparticles that could minimize the use of other inert materials and increase the drug loading content. [42] For example, SN38 was conjugated to oligo-PEG via a thioether and phenol ester bond formation. [43] In aqueous solutions, the drug conjugates formed polymersomes sensitive to glutathione and reactive oxygen species due to the presence of phenol ester and thioether groups.…”

Section: Co-delivery Of Chemical Drugs Using Polymeric Vesiclesmentioning

confidence: 99%

Co‐Delivery of Drugs and Genes Using Polymeric Nanoparticles for Synergistic Cancer Therapeutic Effects

Thambi

Lee

2017

Adv Healthcare Materials

104

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Drug and gene delivery systems based on nanoparticles, microparticles and hydrogels have been widely studied for cancer treatment in the past decade. To achieve an efficient and safe delivery, selection of drug and gene delivery carrier is critical. Biocompatible polymeric nanoparticles are considerably promising carrier candidates in delivery of drugs and genes because of their unique chemical and physical properties. However, delivery of a drug or gene sometimes cannot achieve a satisfactory treatment effect. Therefore, co‐delivery of dual drugs or co‐delivery of a drug and a gene in a polymeric nanoparticle has attracted attention. Such co‐delivery systems can overcome multi‐drug resistance of chemical drugs and achieve a synergistic therapeutic effect. In this progress report, we summarize recent progress in the preparation and application of polymeric drug and gene co‐delivery nanosystems. The remaining challenges and future trends in this field are also included.

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“…Shen etc took the advantage of the strong hydrophobicity of camptothecin and conjugated it with short oligo ethylene glycol (OEG) (42). Both single and dual CPT conjugates (OEG-CPT, OEG-DiCPT) self-assem- bled into liposome-like nanoparticles with drug loading as high as 58 wt% (Figure 2c).…”

Section: Introductionmentioning

confidence: 99%

Nanosized Camptothecin Conjugates for Single and Combined Drug Delivery

Chen¹,

Sun²,

Wang³

et al. 2016

Eur J Bio Med Res

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Camptothecin (CPT), a natural DNA topoisomerase 1 inhibitor, is commonly used as a model hydrophobic compound for anticancer drug delivery research. Nanoparticle loaded with active drugs has the potential to selectively deliver the therapeutic agents into tumor cells without affecting the normal tissues, and hence is attracting tremendous attention from biomedical scientists. Nanoparticles can benefit from the enhanced permeability and retention effect (EPR) of the tumor tissues that allows nanoparticles to be transported through the leaky blood vessels and retained for a longer time compared with traditional small molecule drugs. In particular, covalent camptothecin conjugates are of extensive interest due to their robust stability by covalent chemical bonding. In this mini-review, recent progress of nanosized camptothecin conjugates will be discussed with the focus on the difference of delivery materials as well as their potential of combined drug delivery for the therapy of cancer.

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Prodrugs Forming High Drug Loading Multifunctional Nanocapsules for Intracellular Cancer Drug Delivery

Cited by 544 publications

References 76 publications

Rod‐Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery

Rod‐Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery

Co‐Delivery of Drugs and Genes Using Polymeric Nanoparticles for Synergistic Cancer Therapeutic Effects

Nanosized Camptothecin Conjugates for Single and Combined Drug Delivery

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