Stimulus‐Responsive Short Peptide Nanogels for Controlled Intracellular Drug Release and for Overcoming Tumor Resistance

Lyu, Linna; Liu, Fang; Wang, Xiaoyong; Hu, Ming; Mu, Jing; Cheong, Hao‐Lun; Liu, Gang; Xing, Bengang

doi:10.1002/asia.201601704

Cited by 20 publications

(13 citation statements)

References 46 publications

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“…Many efforts have been made directly towards P-gp inhibition via small molecule drugs such as verapamil (VER) 50 , 51 and cyclosporine A 52 , 53 to restore sensitivity of resistant cancer cells. A combination of various chemotherapeutic drugs into a single platform are often used to prevent P-gp pumping out.…”

Section: Endogenous Stimuli-responsive Nanomedicinesmentioning

confidence: 99%

Stimuli-Responsive Nanomedicines for Overcoming Cancer Multidrug Resistance

2018

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Chemotherapy is still a main option for cancer therapy, but its efficacy is often unsatisfying due to multidrug resistance (MDR). The tumor microenvironment is considered a dominant factor causing MDR. Stimuli-responsive nanomedicines exhibit many superiorities for reversal of MDR. As smart systems, stimuli-responsive nanomedicines are desirable for achieving site-specific accumulation and triggered drug release in response to slight changes in physicochemical properties in pathological conditions or to exogenous stimuli. In this review, we highlight the current progress of various nanomedicines with different stimuli-responsive capabilities for overcoming MDR. The materials, design, construction as well as efficacy in overcoming MDR of these nanomedicines are discussed. Eventually, we look forward to forthcoming intelligent nanoparticle systems with new mechanisms to deliver drugs for practical applications in conquering cancer MDR.

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Section: Endogenous Stimuli-responsive Nanomedicinesmentioning

confidence: 99%

Stimuli-Responsive Nanomedicines for Overcoming Cancer Multidrug Resistance

2018

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“…The supramolecular self-assembly process exists in nature and is closely related to the bioactivity of matter. Due to good manufacturing practices, biocompatibility and designable bioactivity, peptides have been used as building blocks to construct different supramolecular nanomaterials for drug delivery 14-17, cell cultures 17-20 and regenerative medicine 21, 22, etc 23-25. In the field of immunomodulation, pioneering studies have demonstrated that supramolecular self-assembled nanomaterials based on peptides as adjuvants could greatly evoke an immune response in the host 26-30.…”

Section: Introductionmentioning

confidence: 99%

A versatile supramolecular nanoadjuvant that activates NF-κB for cancer immunotherapy

Xu¹,

Yang²,

Liu³

et al. 2019

Theranostics

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Although powerful adjuvants hold promise of vaccines for cancer immunotherapy, cumbersome preparation processes, elusive mechanisms and failure to induce T cell responses have largely limited their clinical translation. Due to their ease of synthesis, good biocompatibility and designable bioactivity, peptide derivatives-based supramolecular nanomaterials have attracted increasing interest in improving the immunogenicity of cancer vaccines. Methods : Herein, we synthesized an NF-κB-activating supramolecular nanoadjuvant (3DSNA) that is prepared by pH-triggering self-assembly of a positively charged D-configurational peptide derivative. The immunostimulatory activity of 3DNSA was explored in vitro and in vivo . Results : 3DSNA can strongly absorb the model antigen (ovalbumin, OVA) through electrostatic interaction. Then, 3DSNA promotes ingestion and cross-presentation of OVA, upregulation of costimulatory factors (CD80 and CD86) and secretion of proinflammatory cytokines (IL-6 and IL-12) by dendritic cells (DCs), accompanied by activation of the innate immune response (NF-κB signaling), resulting in long-term antigen-specific memory and effector CD8 + T cells response. When compared with conventional aluminum hydroxide adjuvant and the corresponding L-configurational supramolecular nanoadjuvant (3LSNA), 3DSNA-adjuvanted OVA (3DSNA+OVA) significantly prevents oncogenesis in naïve mice with a complete response rate of 60 %, restrains the tumor growth and prolongs the survival of melanoma-bearing mice. Conclusion : These findings demonstrate that 3DSNA is a promising neo-adjuvant that enables various vaccines to be therapeutic for many important diseases including cancer.

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“…[1][2][3][4][5][6] However,l eakage of the toxic drugs encapsulatedi nt he self-assemblies may occur along with circulation, which can lead to damage to normal tissue. [1][2][3][4][5][6] However,l eakage of the toxic drugs encapsulatedi nt he self-assemblies may occur along with circulation, which can lead to damage to normal tissue.…”

Section: Introductionmentioning

confidence: 99%

“…Nano self-assemblies, which are efficiently used for the passive targetingo fh ydrophobic drugs by the enhancedp ermeability and retention (EPR) effect, have been demonstrated to be effective in the biomedical field. [1][2][3][4][5][6] However,l eakage of the toxic drugs encapsulatedi nt he self-assemblies may occur along with circulation, which can lead to damage to normal tissue. [7,8] To avoid this phenomenon in the chemical therapy process, much attention has been focused on polymer-drug conjugates to enhance the poor bioavailability of these chemical drugs.…”

Section: Introductionmentioning

confidence: 99%

“…Nano self‐assemblies, which are efficiently used for the passive targeting of hydrophobic drugs by the enhanced permeability and retention (EPR) effect, have been demonstrated to be effective in the biomedical field . However, leakage of the toxic drugs encapsulated in the self‐assemblies may occur along with circulation, which can lead to damage to normal tissue .…”

Section: Introductionmentioning

confidence: 99%

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Photo‐ and pH‐ Dual‐Responsive β‐Cyclodextrin‐Based Supramolecular Prodrug Complex Self‐Assemblies for Programmed Drug Delivery

Bai

Liu

Song

et al. 2018

Chemistry An Asian Journal

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Despite the fact that progress has been made in the application of supramolecular prodrug self-assembliest o enhance the functionality of drug-delivery systems, corresponding research on multi-responsive supramolecular prodrug self-assemblies for programmedd rug delivery is still limited. In this paper,t he synthesis and self-assembly behavior of supramolecularp rodrug complexes( SPCs) with b-cyclodextrin-acylhydrazone-doxorubicin (b-CD-hydrazone-DOX) and the targeting of azobenzene-terminated poly[2-(dimethylamino)ethyl methacrylate] (Azo-PDMA-FA) as a building block were investigated. The obtained SPCs could also form self-assemblies on the basis of their amphiphilic nature. Next, SPC-based multi-compartment vesiclesa nd complex micelles, which were confirmed by transmission electron microscopy and dynamic/static light scattering, were obtained with good reversibility under alternative visible light or UV irradiation. Furthermore, three-stage programmed drug-delivery behavior was observed from dual-re-sponsiveS PC-based self-assemblies by utilizing UV and pH stimuli.S pecifically,t he SPCs first self-assembled into multicompartmental vesicles, which was accompanied by as low releaseo fD OX. Next, UV-light irradiation induced the dissociation of b-CD/Azo,w hich led to morphologyt ransition and as light increaseinthe rate of releaseofDOX. Upon transferring the self-assemblies to phosphate-buffer solution (pH 5.0), the releaser ates increased notably as ar esult of the broken acylhydrazone bond. Finally,b asic cell experiments further demonstrated that the SPC-based self-assemblies could be internalized into cancerc ells, which suggests their promise for applicationsinc ancer therapy.Scheme1.Morphology transition of supramolecular prodrugcomplex self-assemblies and their programmed drug-release behaviorregulated by UV lighta nd pH.

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Stimulus‐Responsive Short Peptide Nanogels for Controlled Intracellular Drug Release and for Overcoming Tumor Resistance

Cited by 20 publications

References 46 publications

Stimuli-Responsive Nanomedicines for Overcoming Cancer Multidrug Resistance

Stimuli-Responsive Nanomedicines for Overcoming Cancer Multidrug Resistance

A versatile supramolecular nanoadjuvant that activates NF-κB for cancer immunotherapy

Photo‐ and pH‐ Dual‐Responsive β‐Cyclodextrin‐Based Supramolecular Prodrug Complex Self‐Assemblies for Programmed Drug Delivery

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