Intelligent Polymeric Nanocarriers Responding to Physical or Biological Signals: A New Paradigm of Cytosolic Drug Delivery for Tumor Treatment

Lee, Bo Reum; Baik, Hye Jung; Oh, Nam Muk; Lee, Eun Seong

doi:10.3390/polym2020086

Cited by 14 publications

(7 citation statements)

References 106 publications

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“…This enzymatic activation transformed the diblock copolymers to become amphiphilic, leading to their self-assembly into spherical colloidal nanostructures. Interestingly, when following the degree of dephosphorylation directly by 31 P NMR, a substantial amount of phosphate groups (∼40% for the shorter block with degree of polymerization (DP) of 13 and ∼10% for a longer block with DP of 30) remained on the styrenic block. Further evidence for the residual phosphate groups was revealed in a fluorescent assay using pyrene, which indicated greater polarity of the enzymatically assembled structures in comparison with the fully dephosphorylated amphiphilic block copolymer, which was used as a control.…”

Section: ■ Limited Enzymatic Degradation Of Polymeric Assembliesmentioning

confidence: 99%

“…Many release mechanisms have been explored, ranging from simple diffusion of the drugs from the carrier to more sophisticated stimuli-responsive polymeric micelles − that can release the drug on demand in response to specific stimuli. These include changes in temperature − and pH, − irradiation with UV–vis light, − or the presence of analytes such as thiols. − Among the various types of stimuli, enzymatic activation or degradation may offer great potential due to the overexpression of specific enzymes in different diseases. − For example, enzymes such as matrix metalloproteinases or cathepsin B, which are overexpressed in various types of cancer, can potentially be utilized to trigger the release of chemotherapeutic drugs selectively at the site of the tumor.…”

Section: Introductionmentioning

confidence: 99%

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Using High Molecular Precision to Study Enzymatically Induced Disassembly of Polymeric Nanocarriers: Direct Enzymatic Activation or Equilibrium-Based Degradation?

Slor

Amir

2021

Macromolecules

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Enzyme-responsive polymers and their assemblies offer great potential to serve as key materials for the design of drug delivery systems and other biomedical applications. However, the utilization of enzymes to trigger the disassembly of polymeric amphiphiles, such as micelles, also suffers from the limited accessibility of the enzyme to moieties that are hidden inside the assembled structures. In this Perspective, we will discuss examples for the utilization of high molecular precision that dendritic structures offer to study the enzymatic degradation of polymeric amphiphiles with high resolution. Up to date, several different amphiphilic systems based on dendritic blocks have all shown that small changes in the hydrophobicity and amphiphilicity strongly affected the degree and rate of enzymatic degradation. The ability to observe the huge effects due to relatively small variations in the molecular structure of polymers can explain the limited enzymatic degradation that is often observed for many reported polymeric assemblies. The observed trends imply that the enzymes cannot reach the hydrophobic core of the micelles, and instead, they gain access to the amphiphiles by the unimer–micelle equilibrium, making the unimer exchange rate a key parameter in tuning the enzymatic degradation rate. Several approaches that are aimed at overcoming the stability–responsiveness challenge are discussed as they open the way to the design of stable and yet enzymatically responsive polymeric nanocarriers.

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Section: ■ Limited Enzymatic Degradation Of Polymeric Assembliesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Using High Molecular Precision to Study Enzymatically Induced Disassembly of Polymeric Nanocarriers: Direct Enzymatic Activation or Equilibrium-Based Degradation?

Slor

Amir

2021

Macromolecules

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“…Consequently, targeted drug release can be more conveniently (or even routinely) realized. Once the hybrid senses a particular chemical from the surrounding environment, it releases the drug automatically [29,30].…”

Section: Discussionmentioning

confidence: 99%

Water-responsive shape memory hybrid: Design concept and demonstration

Fan¹,

Huang²,

Wang³

et al. 2011

Express Polym. Lett.

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Abstract. Shape memory materials are featured by their ability to recover their original shapes when a particular stimulus, such as heat, light, magnetic field, even moisture/water, etc. is applied. However, it is not an easy task for non-professionals to synthesize a shape memory material which can meet all the requirements of a particular application. Even for professionals, like materials researchers, it could involve tedious trial and error procedures. In this paper, the concept of water-responsive shape memory hybrid is proposed and the advantages are demonstrated by two examples. The hybrid concept is versatile and can be easily accessed by those even without much polymer/chemistry background. Moreover, the performance of such hybrids can be well-predicted. This concept can be further extended into solvent-responsive shape memory hybrids, which can be routinely designed and realized in a Do-It-Yourself manner by almost anyone.

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“…[38][39][40][41][42][43] Among others, thermo-responsive polymers are particularly attractive because they show a drastic change in physico-chemical characteristics as a result of phase transition upon heating. 44,45 Poly(N-isopropylacrylamide) (PNIPAM) is one of the most well-known temperature sensitive polymers applied for the synthesis of macrogels and microgels (MG).…”

Section: Introductionmentioning

confidence: 99%

“…a Fraunhofer Institute for Cell Therapy and Immunology, Am Mu ¨hlenberg 13, Stimuli-responsive materials play an important role in nonbiological and biological applications such as drug-delivery, sensing, diagnostics, tissue engineering, etc. [38][39][40][41][42][43] Among others, thermo-responsive polymers are particularly attractive because they show a drastic change in physico-chemical characteristics as a result of phase transition upon heating. 44,45 Poly(N-isopropylacrylamide) (PNIPAM) is one of the most well-known temperature sensitive polymers applied for the synthesis of macrogels and microgels (MG).…”

Section: Introductionmentioning

confidence: 99%

Temperature-induced molecular transport through polymer multilayers coated with PNIPAM microgels

Vikulina

Aleed

Paulraj

et al. 2015

Phys. Chem. Chem. Phys.

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Polyelectrolyte multilayers serve as effective reservoirs for bioactive molecules which are stored and released from the multilayers for cellular applications. However, control over the release without significantly affecting the multilayers and biomolecules is still a challenge. On the other hand, externally stimulated release would make the multilayers promising for the development of stimuli-sensitive planar carriers with release performance switched on demand. In this study soft composite films are designed by coating hyaluronic acid/poly-L-lysine (HA/PLL) multilayers with temperature responsive poly-(N-isopropylacrylamide) (PNIPAM) microgels. Microgels are flattened and immersed into the multilayers to maximize the number of contacts with the surrounding polyelectrolytes (HA and PLL). The microgel coating serves as an efficient switchable barrier for the PLL transport into the multilayers. PLL diffusion into the film is significantly hindered at room temperature but is dramatically enhanced at 40 1C above the volume phase transition temperature (VPTT) of PNIPAM at 32 1C associated with microgel shrinkage. Scanning force microscopy micrographs show that the mechanism of volume phase transition on soft surfaces cannot be directly deduced from the processes taking place at solid substrates.

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Intelligent Polymeric Nanocarriers Responding to Physical or Biological Signals: A New Paradigm of Cytosolic Drug Delivery for Tumor Treatment

Cited by 14 publications

References 106 publications

Using High Molecular Precision to Study Enzymatically Induced Disassembly of Polymeric Nanocarriers: Direct Enzymatic Activation or Equilibrium-Based Degradation?

Using High Molecular Precision to Study Enzymatically Induced Disassembly of Polymeric Nanocarriers: Direct Enzymatic Activation or Equilibrium-Based Degradation?

Water-responsive shape memory hybrid: Design concept and demonstration

Temperature-induced molecular transport through polymer multilayers coated with PNIPAM microgels

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