Alliance with EPR Effect: Combined Strategies to Improve the EPR Effect in the Tumor Microenvironment

Park, Jooho; Choi, Yongwhan; Chang, Hyeyoun; Um, Wooram; Ryu, Jee Hoon; Kwon, Ick Chan

doi:10.7150/thno.37198

Cited by 255 publications

(197 citation statements)

References 144 publications

(157 reference statements)

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“…However, clinical studies demonstrated that compared to murine experimental tumors the EPR level in human tumors was less pronounced and could differ substantially not only between the same type tumors in different patients, but also between various sites of metastasis in a single patient [156]. In attempts to overcome instability of nanoparti cles it was suggested to make them functionally addressed by, for example, attaching EGFR specific ligands [157,158].…”

Section: The Use Of Egfr As a Delivery Systemmentioning

confidence: 99%

Epidermal Growth Factor Receptor: Key to Selective Intracellular Delivery

Rosenkranz

Slastnikova

2020

Biochemistry Moscow

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Epidermal growth factor receptor (EGFR) is an integral surface protein mediating cellular response to a number of growth factors. Its overexpression and increased activation due to mutations is one of the most common traits of many types of cancer. Development and clinical use of the agents, which block EGFR activation, became a prime example of the personalized targeted medicine. However, despite the obvious success in this area, cancer cure remains unattainable in most cases. Because of that, as well as the result of the search for possible ways to overcome the difficulties of treatment, a huge number of new treatment methods relying on the use of EGFR overexpression and its changes to destroy cancer cells. Modern data on the structure, functioning, and intracellular transport of EGFR, its natural ligands, as well as signaling cascades triggered by the EGFR activation, peculiarities of the EGFR expression and activation in oncological disorders, as well as applied therapeutic approaches aimed at blocking EGFR signaling pathway are summarized and analyzed in this review. Approaches to the targeted delivery of various chemotherapeutic agents, radionuclides, immunotoxins, photosensitizers, as well as the prospects for gene therapy aimed at cancer cells with EGFR overexpression are reviewed in detail. It should be noted that increasing attention is being paid nowadays to the development of multifunctional systems, either carrying several different active agents, or possessing several environment-dependent transport functions. Potentials of the systems based on receptor-mediated endocytosis of EGFR and their possible advantages and limitations are discussed.

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Section: The Use Of Egfr As a Delivery Systemmentioning

confidence: 99%

Epidermal Growth Factor Receptor: Key to Selective Intracellular Delivery

Rosenkranz

Slastnikova

2020

Biochemistry Moscow

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“…or internal (pH, enzymatic, redox, etc.) stimulus to produce the local release of the drug [7,8]. In particular, pH has been used for a long time as a critical feature for the differentiation between healthy tissues and abnormal tissues.…”

Section: Introductionmentioning

confidence: 99%

Characterization and Therapeutic Effect of a pH Stimuli Responsive Polymeric Nanoformulation for Controlled Drug Release

et al. 2020

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Despite the large number of polymeric nanodelivery systems that have been recently developed, there is still room for improvement in terms of therapeutic efficiency. Most reported nanodevices for controlled release are based on drug encapsulation, which can lead to undesired drug leakage with a consequent reduction in efficacy and an increase in systemic toxicity. Herein, we present a strategy for covalent drug conjugation to the nanodevice to overcome this drawback. In particular, we characterize and evaluate an effective therapeutic polymeric PEGylated nanosystem for controlled pH-sensitive drug release on a breast cancer (MDA-MB-231) and two lung cancer (A549 and H520) cell lines. A significant reduction in the required drug dose to reach its half maximal inhibitory concentration (IC50 value) was achieved by conjugation of the drug to the nanoparticles, which leads to an improvement in the therapeutic index by increasing the efficiency. The genotoxic effect of this nanodevice in cancer cells was confirmed by nucleus histone H2AX specific immunostaining. In summary, we successfully characterized and validated a pH responsive therapeutic polymeric nanodevice in vitro for controlled anticancer drug release.

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“…Hyaluronic acid (HA) terminal groups were attached to PAMAM core through PLGLAG peptide linkages, which can be cleaved by MMP-2 at tumor sites, and the dendrimer will shrink from ~200 to ~10 nm. The size shrinkage property benefits the cleaved dendrimers in the enhanced permeability and retention (EPR) effect, thus improving the cellular uptake of nanoparticles [ 132 , 133 ]. Liu et al also employed MMP2-sensitive peptide (GPLGIAGQ) in generation 4 PAMAM dendrimers for delivering cytotoxic peptide KLAK [ 118 ].…”

Section: Dendrimersmentioning

confidence: 99%

Dendrimers as Modulators of Brain Cells

2020

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Nanostructured hyperbranched macromolecules have been extensively studied at the chemical, physical and morphological levels. The cellular structural and functional complexity of neural cells and their cross-talk have made it rather difficult to evaluate dendrimer effects in a mixed population of glial cells and neurons. Thus, we are at a relatively early stage of bench-to-bedside translation, and this is due mainly to the lack of data valuable for clinical investigations. It is only recently that techniques have become available that allow for analyses of biological processes inside the living cells, at the nanoscale, in real time. This review summarizes the essential properties of neural cells and dendrimers, and provides a cross-section of biological, pre-clinical and early clinical studies, where dendrimers were used as nanocarriers. It also highlights some examples of biological studies employing dendritic polyglycerol sulfates and their effects on glia and neurons. It is the aim of this review to encourage young scientists to advance mechanistic and technological approaches in dendrimer research so that these extremely versatile and attractive nanostructures gain even greater recognition in translational medicine.

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Alliance with EPR Effect: Combined Strategies to Improve the EPR Effect in the Tumor Microenvironment

Cited by 255 publications

References 144 publications

Epidermal Growth Factor Receptor: Key to Selective Intracellular Delivery

Epidermal Growth Factor Receptor: Key to Selective Intracellular Delivery

Characterization and Therapeutic Effect of a pH Stimuli Responsive Polymeric Nanoformulation for Controlled Drug Release

Dendrimers as Modulators of Brain Cells

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