Polymeric nanovehicles for anticancer drugs with triggering release mechanisms

Oh, Kyung Taek; Yin, Hongxi; Lee, Eun Seong; Bae, You Han

doi:10.1039/b707142f

Cited by 184 publications

(148 citation statements)

References 144 publications

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“…80 The amide group linking the PEG chains to the DOX molecules was designed so that it could be cleaved under the desired conditions, that is, by a specific enzyme present in the cell's lysosomes. 81,82 Nowadays, it is acknowledged that the efficacy of chemotherapeutic drugs is in many cases hindered not only by dose-limiting side effects but also by poor bioavailability at the disease site. In the specific case of DOX, the chemical structure of this chemotherapeutic agent presents a primary amine with a basic pK a .…”

Section: Discussionmentioning

confidence: 99%

Targeted polyethylene glycol gold nanoparticles for the treatment of pancreatic cancer: from synthesis to proof-of-concept in vitro studies

Spadavecchia¹,

Movia²,

Moore³

et al. 2016

IJN

167

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International audienceThe main objective of this study was to optimize and characterize a drug delivery carrier for doxorubicin, intended to be intravenously administered, capable of improving the therapeutic index of the chemotherapeutic agent itself, and aimed at the treatment of pancreatic cancer. In light of this goal, we report a robust one-step method for the synthesis of dicarboxylic acid-terminated polyethylene glycol (PEG)-gold nanoparticles (AuNPs) and doxorubicin-loaded PEG-AuNPs, and their further antibody targeting (anti-Kv11.1 polyclonal antibody [pAb]). In in vitro proof-of-concept studies, we evaluated the influence of the nanocarrier and of the active targeting functionality on the anti-tumor efficacy of doxorubicin, with respect to its half-maximal effective concentration (EC50) and drug-triggered changes in the cell cycle. Our results demonstrated that the therapeutic efficacy of doxorubicin was positively influenced not only by the active targeting exploited through anti-Kv11.1-pAb but also by the drug coupling with a nanometer-sized delivery system, which indeed resulted in a 30-fold decrease of doxorubicin EC50, cell cycle blockage, and drug localization in the cell nuclei. The cell internalization pathway was strongly influenced by the active targeting of the Kv11.1 subunit of the human Ether-à-go-go related gene 1 (hERG1) channel aberrantly expressed on the membrane of pancreatic cancer cells. Targeted PEG-AuNPs were translocated into the lysosomes and were associated to an increased lysosomal function in PANC-1 cells. Additionally, doxorubicin release into an aqueous environment was almost negligible after 7 days, suggesting that drug release from PEG-AuNPs was triggered by enzymatic activity. Although preliminary, data gathered from this study have considerable potential in the application of safe-by-design nano-enabled drug-delivery systems (ie, nanomedicines) for the treatment of pancreatic cancer, a disease with a poor prognosis and one of the main current burdens of today’s health care bill of industrialized countries

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Section: Discussionmentioning

confidence: 99%

Targeted polyethylene glycol gold nanoparticles for the treatment of pancreatic cancer: from synthesis to proof-of-concept in vitro studies

Spadavecchia¹,

Movia²,

Moore³

et al. 2016

IJN

167

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“…In all measurements (involving either invasive or noninvasive methods) of the pH e of human and animal solid tumors, more than 80% of all measured values consistently fall below a pH of 7.2 [27][28][29]. The development of pH-sensitive drug-carriers therefore maybe a unique strategy and confer advantages over using external stimuli, such as hyperthermia [5] and ultrasound [6] which require exact location of tumors for triggered release [30].…”

Section: Introductionmentioning

confidence: 99%

Tumor pH-responsive flower-like micelles of poly(l-lactic acid)-b-poly(ethylene glycol)-b-poly(l-histidine)

Lee

Kim

et al. 2007

Journal of Controlled Release

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412

267

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Polymeric micelles were constructed from poly(L-lactic acid) (PLA; M n 3K)-b-poly(ethylene glycol) (PEG; M n 2K)-b-poly(L-histidine) (polyHis; M n 5K) as a tumor pH-specific anticancer drug carrier. Micelles (particle diameter: ~ 80 nm; critical micelle concentration (CMC): 2 µg/ml) formed by dialysis of the polymer solution in dimethylsulfoxide (DMSO) against pH 8.0 aqueous solution, are assumed to have a flower-like assembly of PLA and polyHis blocks in the core and PEG block as the shell. The pH-sensitivity of the micelles originates from the deformation of the micellar core due to the ionization of polyHis at a slightly acidic pH. However, the co-presence of pH-insensitive lipophilic PLA block in the core prevented disintegration of the micelles and caused swelling/ aggregation. A fluorescence probe study showed that the polarity of pyrene retained in the micelles increased as pH was decreased from 7.4 to 6.6, indicating a change to a more hydrophilic environment in the micelles. Considering that the size increased up to 580 nm at pH 6.6 from 80 nm at pH 7.4 and that the transmittance of micellar solution increased with decreasing pH, the micelles were not dissociated but rather swollen/aggregated. Interestingly, the subsequent decline of pyrene polarity below pH 6.6 suggested re-self-assembly of the block copolymers, most likely forming a PLA block core while polyHis block relocation to the surface. Consequently, these pH-dependent physical changes of the PLA-b-PEG-b-polyHis micelles provide a mechanism for triggered drug release from the micelles triggered by the small change in pH (pH 7.2-6.5).

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“…Among organic nanoparticles we can find dendrimers [43], liposomes [44,45], polymers [46,47], and virus-like particles [48].…”

Section: Their Applications As Drug Delivery Systemsmentioning

confidence: 99%

Mesoporous Silica Nanoparticles: Their Projection in Nanomedicine

Vallet‐Regí

2012

ISRN Materials Science

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Mesoporous silica nanoparticles are receiving growing attention by the scientific biomedical community. Among the different types of inorganic nanomaterials, mesoporous silica nanoparticles have emerged as promising multifunctional platforms for nanomedicine. Since their introduction in the drug delivery landscape in 2001, mesoporous materials for drug delivery are receiving growing scientific interest for their potential applications in the biotechnology and nanomedicine fields. The ceramic matrix efficiently protects entrapped guest molecules against enzymatic degradation or denaturation induced by pH and temperature as no swelling or porosity changes take place as a response to variations in the surrounding medium. It is possible to load huge amounts of cargo into the mesopore voids and capping the pore entrances with different nanogates. The application of a stimulus provokes the nanocap removal and triggers the departure of the cargo. This strategy permits the design of stimuliresponsive drug delivery nanodevices.

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Polymeric nanovehicles for anticancer drugs with triggering release mechanisms

Cited by 184 publications

References 144 publications

Targeted polyethylene glycol gold nanoparticles for the treatment of pancreatic cancer: from synthesis to proof-of-concept in vitro studies

Targeted polyethylene glycol gold nanoparticles for the treatment of pancreatic cancer: from synthesis to proof-of-concept in vitro studies

Tumor pH-responsive flower-like micelles of poly(l-lactic acid)-b-poly(ethylene glycol)-b-poly(l-histidine)

Mesoporous Silica Nanoparticles: Their Projection in Nanomedicine

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