Advances in Stimulus‐Responsive Polymeric Materials for Systemic Delivery of Nucleic Acids

Sun, Minjie; Wang, Kaikai; Oupický, David

doi:10.1002/adhm.201701070

Cited by 37 publications

(32 citation statements)

References 152 publications

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“…For this reason, GSH-responsive NPs have been recognized as promising intracellular drug delivery systems for cancer therapy. [12][13][14][15] Several recent reviews have discussed redox responsive gene delivery polyplexes, liposomes, micelles, nanoparticles, gels and antibody-drug conjugates [12,16,17]. One example is Mylotarg®, which was the first FDA approved drug delivery system containing a linker system with a disulfide bond [18], although this product was subsequently withdrawn from the market.…”

Section: Introductionmentioning

confidence: 99%

Enhanced uptake in 2D- and 3D- lung cancer cell models of redox responsive PEGylated nanoparticles with sensitivity to reducing extra- and intracellular environments

Conte

Mastrotto

Taresco

et al. 2018

Journal of Controlled Release

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In the treatment of lung cancer, there is an urgent need of innovative medicines to optimize pharmacological responses of conventional chemotherapeutics while attenuating side effects. Here, we have exploited some relatively unexplored subtle differences in reduction potential, associated with cancer cell microenvironments in addition to the well-known changes in intracellular redox environment. We report the synthesis and application of novel redox-responsive PLGA (poly(lactic-co-glycolic acid)) -PEG (polyethylene glycol) nanoparticles (RR-NPs) programmed to change surface properties when entering tumor microenvironments, thus enhancing cell internalization of the particles and their drug cargo. The new co-polymers, in which PEG and PLGA were linked by 'anchiomeric effector' dithiylethanoate esters, were synthesized by a combination of ring-opening polymerization and Michael addition reactions and employed to prepare NPs. Non redox-responsive nanoparticles (nRR-NPs) based on related PLGA-PEG copolymers were also prepared as comparators. Spherical NPs of around 120 nm diameter with a low polydispersity index and negative zeta potential as well as good drug loading of docetaxel were obtained. The NPs showed prolonged stability in relevant simulated biological fluids and a high ability to penetrate an artificial mucus layer due to the presence of the external PEG coating. Stability, FRET and drug release studies in conditions simulating intracellular reductive environments demonstrated a fast disassembly of the external shell of the NPs, thus triggering on-demand drug release. FACS measurements and confocal microscopy showed increased and faster uptake of RR-NPs in both 2D- and 3D- cell culture models of lung cancer compared to nRR-NPs. In particular, the 'designed-in' reductive instability of RR-NPs in conditioned cell media, the fast PEG release in the extracellular compartment, as well as a diminution of uptake rate in control experiments where extracellular thiols were neutralized, suggested a partial extracellular release of the PEG fringe that promoted rapid internalization of the residual NPs into cells. Taken together, these results provide further evidence of the effectiveness of PEGylated reducible nanocarriers to permeate mucus layer barriers, and establish a new means to enhance cancer cell uptake of drug carriers by extra-and intra-cellular cleavage of protein- and cell-shielding hydrophilic blocks.

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Section: Introductionmentioning

confidence: 99%

Enhanced uptake in 2D- and 3D- lung cancer cell models of redox responsive PEGylated nanoparticles with sensitivity to reducing extra- and intracellular environments

Conte

Mastrotto

Taresco

et al. 2018

Journal of Controlled Release

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“…Linear bioreducible PAAs bearing disulfide linkages in the main chain backbone formed nanocomplexes by selfassembly with DNA, siRNA and proteins and were studied as carriers for their intracellular delivery [117,118]. Linear bioreducibles PAA with different steric hindrance, hence with diversified chemical stability, near the disulfide were synthesized (Scheme 10a) [119].…”

Section: Paas As Dna/sirna Transfection Promotersmentioning

confidence: 99%

Polyamidoamines: Versatile Bioactive Polymers with Potential for Biotechnological Applications

Ranucci¹,

Manfredi²

2019

Chemistry Africa

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Polyamidoamines (PAAs) are multifunctional polymers prepared from prim-or sec-amines by Michael-type polyaddition with bisacrylamides. The reaction is preferably carried out at room temperature in water and without added catalysts or organic solvents. The reaction is specific. The presence in the starting monomers of additional functions, leaving apart amine, thiol and phosphine groups, does not interfere with the polymerization process. Consequently, PAAs are a polymer class endowed with unusual structural versatility. Moreover, at pH > 7 they are hydrolytically degradable in aqueous media to harmless products mostly consisting of β-amino-propionic acids. Many PAAs are remarkably biocompatible notwithstanding their polycationic nature. These properties allow to prepare multifunctional polymeric structures suitable for many diversified applications in biotechnology, such as drug carriers, transfection promoters, antiviral and antimalarial agents, hydrogels scaffolds for tissue engineering. The objective of this paper is to fully report the PAA chemistry and the studied biotechnological applications of a vast PAA library.

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“…Therefore, the intra/extracellular gradient of ATP is another key trigger in the design of responsive delivery systems, which present release behaviors associated with the surrounding ATP levels. To date, three categories have been employed to fabricate these delivery systems: (i) PBA moieties that can bind to diol‐containing molecules (i.e. ATP); (ii) single‐stranded DNA aptamers that specifically bind ATP; and (iii) enzymes that consume ATP as a source of energy .…”

Section: Dynamic and Bioresponsive Processes Have Inspired Designs Inmentioning

confidence: 99%

“…6,49 Therefore, the intra/extracellular gradient of ATP is another key trigger in the design of responsive delivery systems, which present release behaviors associated with the surrounding ATP levels. To date, three categories 23 have been employed to fabricate these delivery systems: (i) PBA moieties that (4) diselenide (se-se) cleavage and DNA release under reductive conditions. Reproduced with permission.…”

Section: Atp-responsive Delivery Systemsmentioning

confidence: 99%

Virus‐inspired and mimetic designs in non‐viral gene delivery

Luo

Liang

Jin

et al. 2019

The Journal of Gene Medicine

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Virus‐inspired mimics for nucleic acid transportation have attracted much attention in the past decade, especially the derivative microenvironment stimuli‐responsive designs. In the present mini‐review, the smart designs of gene carriers that overcome biological barriers and realize an efficient delivery are categorized with respect to the different “triggers” provided by tumor cells, including pH, redox potentials, ATP, enzymes and reactive oxygen species. Some dual/multi‐responsive gene vectors have also been introduced that show a more precise and efficient delivery in the complicated environment of human body. In addition, inspired by the special recognition mechanisms and components of viruses, improvements in the design of carriers relating to targeting/penetration properties, as well as chemical component evolution, are also addressed.

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Advances in Stimulus‐Responsive Polymeric Materials for Systemic Delivery of Nucleic Acids

Cited by 37 publications

References 152 publications

Enhanced uptake in 2D- and 3D- lung cancer cell models of redox responsive PEGylated nanoparticles with sensitivity to reducing extra- and intracellular environments

Enhanced uptake in 2D- and 3D- lung cancer cell models of redox responsive PEGylated nanoparticles with sensitivity to reducing extra- and intracellular environments

Polyamidoamines: Versatile Bioactive Polymers with Potential for Biotechnological Applications

Virus‐inspired and mimetic designs in non‐viral gene delivery

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