Drug Delivery Systems with a “Tumor-Triggered” Targeting or Intracellular Drug Release Property Based on DePEGylation

Ren, Zhe; Liao, Tao; Li, Cao; Kuang, Ying

doi:10.3390/ma15155290

Cited by 6 publications

(4 citation statements)

References 147 publications

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“…In another approach, PEG-coated nanoparticles, which are stable in blood and normal physiological conditions but can be degraded in the TME, can achieve a depegylation-based targeted delivery in the TME and intracellular drug delivery leading to more efficient drug delivery and decreased side effects [62].…”

Section: Nanoparticles Targeting the Acidic Tumor Microenvironmentmentioning

confidence: 99%

Design of Nanoparticles in Cancer Therapy Based on Tumor Microenvironment Properties

et al. 2022

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Cancer is one of the leading causes of death worldwide, and battling cancer has always been a challenging subject in medical sciences. All over the world, scientists from different fields of study try to gain a deeper knowledge about the biology and roots of cancer and, consequently, provide better strategies to fight against it. During the past few decades, nanoparticles (NPs) have attracted much attention for the delivery of therapeutic and diagnostic agents with high efficiency and reduced side effects in cancer treatment. Targeted and stimuli-sensitive nanoparticles have been widely studied for cancer therapy in recent years, and many more studies are ongoing. This review aims to provide a broad view of different nanoparticle systems with characteristics that allow them to target diverse properties of the tumor microenvironment (TME) from nanoparticles that can be activated and release their cargo due to the specific characteristics of the TME (such as low pH, redox, and hypoxia) to nanoparticles that can target different cellular and molecular targets of the present cell and molecules in the TME.

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Section: Nanoparticles Targeting the Acidic Tumor Microenvironmentmentioning

confidence: 99%

Design of Nanoparticles in Cancer Therapy Based on Tumor Microenvironment Properties

et al. 2022

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“…Furthermore, there is a difference in tumor extracellular and intracellular pH values (pH ex = 6.5–7.2 and pH in = 4.5–6.5). The pH‐sensitive linkages, such as hydrazine, 28 benzoic‐imine, 29 thioketal, 30 acetal, 31 and orthoester 32 have been used for conjugation of PEG to carriers. To improve cellular uptake, the shedding of shell should be able to restore the positive surface charge of the nanocarriers at the target site.…”

Section: Introductionmentioning

confidence: 99%

Shell‐sheddable and charge switchable magnetic nanoparticle as pH‐sensitive nanocarrier for targeted drug delivery applications

Aram,

Sadeghi‐Abandansari,

Radmanesh

et al. 2024

Polymers for Advanced Techs

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A pH‐sensitive shell‐sheddable magnetic nanocarrier was prepared based on Fe3O4@SiO2 nanoparticles coated with polyethyleneimine (PEI) and polyethyleneglycol (PEG). The PEI was coated on Fe3O4@SiO2 nanoparticles through an electrostatic attraction and the PEG chains were connected to the PEI via pH‐sensitive benzoic‐imine bonds. The synthesized products and final nanocarrier were characterized with FT‐IR, 1H NMR, dynamic light scattering (DLS), zeta‐potential, TEM, and vibrating‐sample magnetometer (VSM). The PEI, as a middle layer, was used to load the curcumin (an anticancer drug) via van der Waals interactions and the shedding of PEG as a hydrophilic corona at the tumor pH (acidic) could induce the release of the drug. The curcumin loading content was found to be ~15% and curcumin‐loaded magnetic nanoparticles (C‐LMNs) showed more triggered release at the tumor pH (5.6) than physiological pH (7.4). In comparison to pure magnetic nanoparticles (MNs), the C‐LMNs showed more cytotoxicity to human prostate cancer cell (PC‐3) and also resulted in an increased rate of late apoptotic/necrotic PC‐3 cells, assessed by flow cytometry analysis. In conclusion, the C‐LMN as pH‐ and magnetic responsive nanocarrier showed good potential for targeted curcumin delivery in therapy of prostate cancer.

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“…“Dynamic protection” strategies have proven to be an effective method for ensuring the specific phagocytosis of “stealthy” DDSs by cancer cells in the past decade. , DePEGylation is one of the important “dynamic protection” strategies, which depends on the modification of PEG on the surface of DDSs by dynamic chemical bonds. − These dynamic bonds remain stable during blood circulation, ensuring DDS protection by PEG. However, tumor tissues can lead to DePEGylation due to their weakly acidic environment or overexpressed enzymes, exposing the positive charge or targeting ligands. − This, in turn, enhances the uptake of DDSs by cancer cells. Zhang et al proposed the concept of “tumor-triggered targeting” using this approach. , They modified the mesoporous silica nanoparticle (MSN)-based DDS with PEG through a Gly-Gly-Pro-Leu-Gly-Val-Arg-Gly-Arg-Gly-Asp-Lys (GGPLGVRGRGDK) peptide.…”

Section: Introductionmentioning

confidence: 99%

Degradable Mesoporous Silica Nanoparticle/Peptide-Based “Trojan Horse”-like Drug Delivery System for Deep Intratumoral Penetration and Cancer Therapy

Liao,

Liu,

et al. 2024

ACS Appl. Nano Mater.

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For conventional anticancer drug delivery systems (DDSs), it is difficult to endow them with both long circulation in vivo and easy cellular endocytosis by cancer cells as well as the ability to accumulate in tumors through the enhanced permeability and retention (EPR) effect and deep intratumoral penetration. Therefore, their in vivo treatment effects are inadequate. Previous studies have shown that "dynamic protection" strategies can effectively address the difficulty of DDS entry into cancer cells as a result of modifying "stealthy" molecules such as poly(ethylene glycol) (PEG). In this work, a "Trojan horse"-like DDS was fabricated by employing the "dynamic protection" strategy. The DDS was developed using ultrasmall, degradable mesoporous silica nanoparticles (DS-MSN) that were bridged by a degradable peptide and cross-linked with 4-arm PEG-N 3 through click chemistry. This resulted in DOX-DS-MSN-CD-peptide-PEG with a size of ∼300 nm, which could accumulate in the tumor, following adequate blood circulation. The peptide could be degraded by matrix metalloproteinase-2 (MMP-2), an overexpressed enzyme in tumors, leading to the release of small-sized, tumor-permeable DS-MSN-based carriers. The remaining Arg-Gly-Asp (RGD) peptide on the surface provides the carriers with a "tumor-triggered targeting" capability. DS-MSN, which includes disulfide bonds in its backbone, could be degraded due to glutathione (GSH) in cancer cells and release of the loaded doxorubicin hydrochloride (DOX). In vitro and in vivo experiments showed that DOX-DS-MSN-CD-peptide-PEG had a prolonged circulation time and tumor accumulation ability, excellent tumor penetration ability, and controlled drug release ability. It operated like a "Trojan horse", overcoming obstacles to deliver the "Greek soldier" DOX to the interior of cancer cells, resulting in effective tumor suppression. This study offers interesting concepts for designing effective and safe drug delivery systems.

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Drug Delivery Systems with a “Tumor-Triggered” Targeting or Intracellular Drug Release Property Based on DePEGylation

Cited by 6 publications

References 147 publications

Design of Nanoparticles in Cancer Therapy Based on Tumor Microenvironment Properties

Design of Nanoparticles in Cancer Therapy Based on Tumor Microenvironment Properties

Shell‐sheddable and charge switchable magnetic nanoparticle as pH‐sensitive nanocarrier for targeted drug delivery applications

Degradable Mesoporous Silica Nanoparticle/Peptide-Based “Trojan Horse”-like Drug Delivery System for Deep Intratumoral Penetration and Cancer Therapy

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