Carrier-free nanoparticles of cathepsin B-cleavable peptide-conjugated doxorubicin prodrug for cancer targeting therapy

Shim, Man Kyu; Park, Jooho; Yoon, Hong Yeol; Lee, Sang‐Min; Um, Wooram; Kim, Jong Ho; Kang, Sung Soo; Seo, Joung Wook; Hyun, Soo Wang; Park, Jae Hyung; Byun, Youngro; Kwon, Ick Chan; Kim, Kwangmeyung

doi:10.1016/j.jconrel.2018.11.032

Cited by 135 publications

(90 citation statements)

References 38 publications

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“…Cathepsin B (C B ), a late endosomal and lysosomal cysteine protease, plays a major role in the progression of human tumors [170] . Taking advantage of this specificity, several C B -cleavable peptide sequences were developed such as VC (Valine-Citrulline) peptides, FRRG (Phenylalanine-Arginine-Arginine-Glycine) peptides and GFLG (Glycine-Phenylalanine-Leucine-Glycine) peptides [170] , [171] , [172] , [173] . Yu and colleagues designed a novel and safe micellar drug carrier for DOX delivery, which was made use of VC dipeptide conjugating hydrophilic mPEG and hydrophobic stearic segment [170] .…”

Section: Stimuli Triggered Drug Deliverymentioning

confidence: 99%

“…Thus, further exploration of the micellar system is needed for a satisfactory drug release behavior. Specially, in a recent study by Zhang et al, a novel type of amide bond-bearing cathepsin B-sensitive gemcitabine (GEM) prodrugs was reported, where the prodrug could in situ covalently target circulating albumin and then made a hitchhike to the tumor [173] . Such a sensitive linker was obtained via the conjugation of 6-maleimidocaproicacid and the amine group of gemcitabine [173] .…”

Section: Stimuli Triggered Drug Deliverymentioning

confidence: 99%

“…Specially, in a recent study by Zhang et al, a novel type of amide bond-bearing cathepsin B-sensitive gemcitabine (GEM) prodrugs was reported, where the prodrug could in situ covalently target circulating albumin and then made a hitchhike to the tumor [173] . Such a sensitive linker was obtained via the conjugation of 6-maleimidocaproicacid and the amine group of gemcitabine [173] . The group confirmed that various cancer cells overexpressed with C B , including HT-29, human breast adenocarcinoma (MDA-MB-231), human breast adenocarcinoma (MCF7) and human lung carcinoma (A549), resulting in successful prodrug activity in these tumor cells.…”

Section: Stimuli Triggered Drug Deliverymentioning

confidence: 99%

“…The group confirmed that various cancer cells overexpressed with C B , including HT-29, human breast adenocarcinoma (MDA-MB-231), human breast adenocarcinoma (MCF7) and human lung carcinoma (A549), resulting in successful prodrug activity in these tumor cells. In detail, in vivo albumin was capable of binding with the maleimide groups of the linker, thus carrying the prodrugs to these tumor [173] . Then triggered by the tumor overexpressed cathepsin B and acidic microenvironment, the system exhibited accelerated release of gemcitabine due to the degradation of amide-containing linker [173] .…”

Section: Stimuli Triggered Drug Deliverymentioning

confidence: 99%

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Tumor microenvironment responsive drug delivery systems

Chen

Yan

et al. 2020

Asian Journal of Pharmaceutical Sciences

156

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Conventional tumor-targeted drug delivery systems (DDSs) face challenges, such as unsatisfied systemic circulation, low targeting efficiency, poor tumoral penetration, and uncontrolled drug release. Recently, tumor cellular molecules-triggered DDSs have aroused great interests in addressing such dilemmas. With the introduction of several additional functionalities, the properties of these smart DDSs including size, surface charge and ligand exposure can response to different tumor microenvironments for a more efficient tumor targeting, and eventually achieve desired drug release for an optimized therapeutic efficiency. This review highlights the recent research progresses on smart tumor environment responsive drug delivery systems for targeted drug delivery. Dynamic targeting strategies and functional moieties sensitive to a variety of tumor cellular stimuli, including pH, glutathione, adenosine-triphosphate, reactive oxygen species, enzyme and inflammatory factors are summarized. Special emphasis of this review is placed on their responsive mechanisms, drug loading models, drawbacks and merits. Several typical multi-stimuli responsive DDSs are listed. And the main challenges and potential future development are discussed.

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Section: Stimuli Triggered Drug Deliverymentioning

confidence: 99%

Section: Stimuli Triggered Drug Deliverymentioning

confidence: 99%

Section: Stimuli Triggered Drug Deliverymentioning

confidence: 99%

Section: Stimuli Triggered Drug Deliverymentioning

confidence: 99%

See 2 more Smart Citations

Tumor microenvironment responsive drug delivery systems

Chen

Yan

et al. 2020

Asian Journal of Pharmaceutical Sciences

156

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“…They showed that the Iron Oxide nanocarrier enhances the anticancer effect of Cisplatin agent with minimized side effects. Even though nanocarrier‐based approaches enhanced therapeutic efficacy, there are still several issues which need to be addressed, including toxicity issues, low drug loading capacity, complexity of designing a multidrug nanovector and lack broad applicability . Instead of using any nanocarrier‐based drug delivery system, carrier‐free (self‐delivery) prodrugs have drawn many pharmacists attention due to their biocompatibility and simple structure .…”

Section: Introductionmentioning

confidence: 99%

Evaluation the synergistic antitumor effect of methotrexate–camptothecin codelivery prodrug from self‐assembly process to acid‐catalyzed both drugs release: A comprehensive theoretical study

2020

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Therapeutic efficiency of amphiphilic methotrexate-camptothecin (MTX-CPT) prodrug compared to free drug mixture (MTX/CPT) has been investigated using allatom molecular dynamics simulation and first principles density functional theory calculations. This comparison revealed that MTX-CPT prodrug tends to form spherical self-assembled nanoparticle (NP), while free MTX/CPT mixture forms rod-shape NP. These observations are attributed to a structural defect in the MTX-CPT prodrug and solvation free energies of MTX, CPT and MTX-CPT molecules. The results provided evidence that noncovalent interactions (NCIs) among the pharmaceutical drugs play a very important role in anticancer agents aggregation process, leading to enhanced stability of the self-assembled NPs. It is found that the stability of MTX-CPT self-assembled NP is greater than the MTX/CPT NP due to the synergistic effect of hydrogen bonding between monomers and solvent (water). Moreover, the noncatalyzed as well as catalyzed hydrolysis reactions of MTX-CPT prodrug are theoretically studied at the PCM(water)//M06-2X/6−31G(d,p) computational level to shed additional light on the role of acidic condition in tumor tissues. We found that the ester hydrolysis in mild acidic solutions is a concerted reaction. In an agreement between theory and experiment, we also confirmed that the activation energies of the catalyzed-hydrolysis steps are much lower than the activation energies of the corresponding steps in the noncatalyzed reaction. Thus, the MTX-CPT prodrug reveals very promising properties as a pH-controlled drug delivery system. K E Y W O R D Sacid-catalyzed ester hydrolysis,

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Implantable MicroLED‐Mediated Chemo‐Photodynamic Combination Therapy for Glioma Treatment

Kim,

Lee,

Park

et al. 2024

Adv Funct Materials

Self Cite

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Photodynamic therapy shows promise for glioma treatment with powerful efficacy and low resistance, however, its effectiveness is significantly lowered by inadequate light delivery through the skull. Herein, a needle‐type implantable microLED device and cathepsin B‐responsive prodrug nanoparticles (PNPs) are newly exploited for glioma's chemo‐photodynamic combination therapy. The microLED containing four small LEDs on the tip of its guide needle can be implanted into the center of glioma tissues without large area opening of skull, uniformly irradiating light to deep glioma tissues. PNPs are formulated via self‐assembly of heterobifunctional prodrug composed of doxorubicin, verteporfin, and cathepsin B‐cleavable peptide linker, wherein they stably maintain inactive nanoparticle structures in normal physiological conditions and specifically deliver therapeutic age to cathepsin B‐overexpressed glioma tissues. In vitro cellular assays, PNPs irradiated with showed the synergistic cytotoxicity of DOX and VFP only in cathepsin B‐overexpressed cancer cells rather than normal cells. In tumor‐bearing mice, PNPs showed high tumor accumulation via the nanoparticle‐driven enhanced permeation and retention (EPR) effect and they also exhibited remarkable therapeutic efficacy against glioma under microLED‐mediated light irradiation via chemo‐photodynamic combination therapy. Accordingly, applying microLED with PNPs is an outstanding strategy to defeat glioma with cooperative chemo‐photodynamic effects, minimal invasiveness, and desirable systemic/local safety.

show abstract

Carrier-free nanoparticles of cathepsin B-cleavable peptide-conjugated doxorubicin prodrug for cancer targeting therapy

Cited by 135 publications

References 38 publications

Tumor microenvironment responsive drug delivery systems

Tumor microenvironment responsive drug delivery systems

Evaluation the synergistic antitumor effect of methotrexate–camptothecin codelivery prodrug from self‐assembly process to acid‐catalyzed both drugs release: A comprehensive theoretical study

Implantable MicroLED‐Mediated Chemo‐Photodynamic Combination Therapy for Glioma Treatment

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