Reduction and temperature dually-triggered size-shrinkage and drug release of micelles for synergistic photothermal-chemotherapy of cancer

Wu, Danfeng; Xu, Zhangting; Li, Zhihong; Yuan, Weizhong; Wang, Hai-Quan; Xie, Xiaoyun

doi:10.1016/j.eurpolymj.2021.110535

Cited by 8 publications

(6 citation statements)

References 51 publications

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“…From the AFM images in Figure a,b, Cy-PEG and UrCy-PEG nanogels exhibited well-dispersed spherical morphologies with average diameters of approximately 40–60 and 50–75 nm, respectively. The particle sizes obtained by AFM measurements were slightly smaller than the values determined using DLS, probably due to the shrinkage of nanogels in the dried state . Therefore, the findings above demonstrated that hydrogen-bonded Cy or UrCy moieties within the polymer structure are the most critical factor that induces spontaneous self-assembly of nanogels in water.…”

Section: Resultsmentioning

confidence: 76%

“…The particle sizes obtained by AFM measurements were slightly smaller than the values determined using DLS, probably due to the shrinkage of nanogels in the dried state. 41 Therefore, the findings above demonstrated that hydrogen-bonded Cy or UrCy moieties within the polymer structure are the most critical factor that induces spontaneous self-assembly of nanogels in water.…”

Section: Resultsmentioning

confidence: 91%

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Hydrogen Bond Strength-Mediated Self-Assembly of Supramolecular Nanogels for Selective and Effective Cancer Treatment

et al. 2021

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This study provides a significant contribution to the development of multiple hydrogen-bonded supramolecular nanocarrier systems by demonstrating that controlling the hydrogen bond strength within supramolecular polymers represents a crucial factor to tailor the drug delivery performance and enhance the effectiveness of cancer therapy. Herein, we successfully developed two kinds of poly(ethylene glycol)-based telechelic polymers Cy-PEG and UrCy-PEG having selfconstituted double and quadruple hydrogen-bonding cytosine (Cy) and ureido-cytosine (UrCy) end-capped groups, respectively, which directly assemble into spherical nanogels with a number of interesting physical characteristics in aqueous solutions. The UrCy-PEG nanogels containing quadruple hydrogen-bonded UrCy dimers exhibited excellent long-term structural stability in a serum-containing biological medium, whereas the double hydrogen-bonded Cy moieties could not maintain the structural integrity of the Cy-PEG nanogels. More importantly, after the drug encapsulation process, a series of in vitro experiments clearly confirmed that drug-loaded UrCy-PEG nanogels induced selective apoptotic cell death in cancer cells without causing significant cytotoxicity to healthy cells, while drug-loaded Cy-PEG nanogels exerted nonselective cytotoxicity toward both cancer and normal cells, indicating that increasing the strength of hydrogen bonds in nanogels plays a key role in enhancing the selective cellular uptake and cytotoxicity of drugs and the subsequent induction of apoptosis in cancer cells.

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Section: Resultsmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 91%

Hydrogen Bond Strength-Mediated Self-Assembly of Supramolecular Nanogels for Selective and Effective Cancer Treatment

et al. 2021

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“…The ICG photothermal activity combined with DOX anticancer action led to promising cytotoxic properties. 102 Yu-Lun et al reported the esterification reaction between bis(2-hydroxyethyl) disulfide and BiBB, which was followed by a ROP reaction for the preparation of PCL-SS-Br. They also used a CuBr/HMTETA catalyst system to polymerize tert -butyl methacrylate ( t BMA) through an ATRP reaction.…”

Section: Copolymers Prepared Through a Combination Of Different Methodsmentioning

confidence: 99%

Synthesis approaches of amphiphilic copolymers for spherical micelle preparation: application in drug delivery

Aliabadi¹,

Hasannia²,

Vakili-Azghandi³

et al. 2023

J. Mater. Chem. B

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“…To enhance drug bioavailability and solubility in water, countless efforts have been made to develop efficacious drug delivery systems. − Due to the desirable advantages, biological stimuli such as enzymes, redox, glucose, pH, and temperature have been commonly applied to the responsive drug release from the drug carriers. − Of these stimuli, reductive sensitivity is especially attractive in the construction of drug delivery systems owing to the different glutathione (GSH) concentrations between the normal body fluids (2–20 μM) and cancer cells (2–20 mM). , Generally, the reduction-responsive nanoparticles were prepared by the introduction of reduction-sensitive linkages or functional groups into their structures. Until now, a series of reduction-responsive nanoparticles including nanogels, micelles, and drug conjugates were used in the preparation of drug delivery systems. − Owing to the promising applications in the delivery of anticancer drugs, nanogels have attracted continuing interest. Lu et al prepared a tailored prodrug nanogel by covalent conjugation of two hydroxyl-group-containing topoisomerase inhibitors, HCPT and DOX, using a reduction-responsive disulfide bond, which served as a therapeutic package for controlled release of both HCPT and DOX within the tumor microenvironment, thus leading to both reinforced chemotherapy and high in vivo biosafety.…”

Section: Introductionmentioning

confidence: 99%

Dual Reduction-Sensitive Nanomicelles for Antitumor Drug Delivery with Low Toxicity to Normal Cells

Li,

Liu,

Liang

et al. 2024

ACS Appl. Nano Mater.

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In this work, a dual-thiol-responsive drug delivery system was fabricated by embedding the reduction-sensitive doxorubicin prodrug (DOX-prodrug) in the reduction-responsive carrier. Therefore, the amphiphilic block copolymer poly(lactide)-SS-poly(2-hydroxyethyl methacrylate) (PLA-SS-PHEMA) was synthesized to be used as an anticancer drug carrier, which would self-assemble into spherical micelles in an aqueous solution with an average diameter of approximately 100 nm. The DOXprodrug could be loaded into the PLA-SS-PHEMA micelles with a high drug loading efficiency (5.27%) and entrapment efficiency (58%). The in vitro release results demonstrated that the cleavage of the intervening disulfide bonds in both the carrier and prodrug in response to a reductive environment led to fast release of the anticancer drug. The cytotoxicity results showed that the dual reduction-sensitive drug delivery system could effectively inhibit tumor cell proliferation, while it had almost no side effects on normal cells. The CLSM results are in agreement with that of flow cytometry, indicating that the drug-loaded micelles could be efficiently internalized into the HeLa cells and the drug is released into the cytoplasm and then enters the nuclei. We further investigated the cell endocytosis mechanism for the micelles, suggesting that the clathrin-mediated endocytosis pathway played the main role in the internalization of this nanocarrier.

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Reduction and temperature dually-triggered size-shrinkage and drug release of micelles for synergistic photothermal-chemotherapy of cancer

Cited by 8 publications

References 51 publications

Hydrogen Bond Strength-Mediated Self-Assembly of Supramolecular Nanogels for Selective and Effective Cancer Treatment

Hydrogen Bond Strength-Mediated Self-Assembly of Supramolecular Nanogels for Selective and Effective Cancer Treatment

Synthesis approaches of amphiphilic copolymers for spherical micelle preparation: application in drug delivery

Dual Reduction-Sensitive Nanomicelles for Antitumor Drug Delivery with Low Toxicity to Normal Cells

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