Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery

Cheng, Ru; Fang, Feng; Meng, Fenghua; Deng, Chao; Feijén, Jan; Zhong, Zhiyuan

doi:10.1016/j.jconrel.2011.01.030

Cited by 1,232 publications

(875 citation statements)

References 106 publications

Supporting

Mentioning

863

Contrasting

Unclassified

Order By: Relevance

“…Tunable release has been a major component of the recent boom in nanomedicine research, as stimuli-responsive carriers are optimized to release payload only upon certain cues either intracellularly or within the microenvironment of tumors and can potentially lower systemic toxicity of chemotherapeutic agents [19][20][21]. Commonly utilized triggers for payload release include a slightly acidic pH in the microenvironment, overexpression of specific enzymes, localized hyperthermia, and increased levels of glutathione within the cell [22][23][24][25][26][27]. Moreover, heightened control over release has grand implications on rational combinatorial therapies since co-delivery does not always imply simultaneous release, and ordered release of multiple therapeutic agents may achieve maximally synergistic effects [28][29][30].…”

Section: Introductionmentioning

confidence: 99%

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

Kemp

Shim

Heo

et al. 2016

Advanced Drug Delivery Reviews

437

258

View full text Add to dashboard Cite

a b s t r a c t a r t i c l e i n f oThe dynamic and versatile nature of diseases such as cancer has been a pivotal challenge for developing efficient and safe therapies. Cancer treatments using a single therapeutic agent often result in limited clinical outcomes due to tumor heterogeneity and drug resistance. Combination therapies using multiple therapeutic modalities can synergistically elevate anti-cancer activity while lowering doses of each agent, hence, reducing side effects. Co-administration of multiple therapeutic agents requires a delivery platform that can normalize pharmacokinetics and pharmacodynamics of the agents, prolong circulation, selectively accumulate, specifically bind to the target, and enable controlled release in target site. Nanomaterials, such as polymeric nanoparticles, gold nanoparticles/cages/shells, and carbon nanomaterials, have the desired properties, and they can mediate therapeutic effects different from those generated by small molecule drugs (e.g., gene therapy, photothermal therapy, photodynamic therapy, and radiotherapy). This review aims to provide an overview of developing multi-modal therapies using nanomaterials ("combo" nanomedicine) along with the rationale, up-to-date progress, further considerations, and the crucial roles of interdisciplinary approaches.

show abstract

Section: Introductionmentioning

confidence: 99%

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

Kemp

Shim

Heo

et al. 2016

Advanced Drug Delivery Reviews

437

258

View full text Add to dashboard Cite

show abstract

“…Moreover, the hydrophobic core made of PCDA should lead to high drug loading and providing effective protection for Cur against hydrolysis. The Biotin-PEG-PCDA NP should be stable during the blood transport but can readily release its API (Cur) once enters the target cancer cells/tissues triggered by the high intracellular glutathione (GSH, 1-10 mM v.s.~10 M in blood) [11] and esterase [12] contents.The over-expressed biotin receptors found on cancer cells can be exploited for effective, active cancer targeting. [13] Importantly, the Biotin-PEG-PCDA NP can be loaded with a 4 second anticancer drug (e.g.…”

mentioning

confidence: 99%

Intracellularly Degradable, Self‐Assembled Amphiphilic Block Copolycurcumin Nanoparticles for Efficient In Vivo Cancer Chemotherapy

Guo

Shen

et al. 2015

Adv Healthcare Materials

View full text Add to dashboard Cite

Chemotherapy is widely used in various cancer treatments. However, current cancer chemotherapy has a major limitation: lacking of specific targeting ability. As a result, it kills both cancerous and healthy cells, causing severe adverse side-effects and toxicity to patients which limits the dose regime and allows tumour to gain resistance. One approach to address this problem is the development of nanoscale drug delivery systems (NDDSs) which can exploit characteristic properties of tumour, such as the enhanced permeation and retention (EPR) effect, [1] and over-expressed cell-surface receptors, [2] to achieve targeted delivery. [3] Despite significant research achievements, most of the current NDDSs, especially those in clinical trials or usage, e.g. drug encapsulated lipids vesicles or polymer micelles, [4] polymerdrug conjugates, and albumin-based nanoparticles, [5] mostly rely on passive targeting and generally lack the ability of active targeting. Moreover, drugs are mostly physically encapsulated or entrapped into the NDDSs, where drug release is mainly achieved via passive diffusion, making it difficult to achieve controlled release, a vital property for high therapeutic 2 efficacy. As a result, most of the drug payloads may have been released before reaching the target sites, leading to reduced therapeutic efficacy and causing adverse side-effects.Furthermore, most NDDSs also suffer from drawbacks such as low drug loading (e.g.antibody-drug conjugates) and/or burst release (e.g. micelles/liposomes). To date, none of the current NDDSs can satisfy all of the requirements of an "idea NDDS" outlined by Langer et al. [3a] To make best use of the advantages of current NDDSs (passive and active targeting delivery to tumour) and overcome their drawbacks (unnecessary and even harmful on-way drug release before entering tumour cells and/or only a small quantity of drugs together with the nano-carriers entering tumour cells) due to the physical incorporation or encapsulation of drugs in NDDSs, which often leads to uncontrolled drug release via diffusion, we take a new approach to prepare NDDSs which is based on so-called poly(active pharmaceutical ingredient) (PAPI) strategy where the APIs are incorporated into an intracellular cleavable polymer backbone (not physically incorporated in drug carriers) in combination with selfassembly characteristics of amphiphilic block copolymers. Here PAPI is defined as a polymer prepared by polycondensation of an API or its derivative having the same or similar bioactivity as a co-or sole-monomer. Considerable advantages here are that the physicalchemical properties of the PAPIs can be readily tailored by changing co-monomers or via chemical modifications. The PAPIs can be further made into various NDDSs where the API release can be controlled via stimuli triggered polymer degradation, overcoming the drawback of un-controlled, diffusion based drug release character commonly experienced in physically incorporated systems. In principle, any drug molecules/derivatives containi...

show abstract

“…This approach takes advantage from the highly reducing environment of cell cytoplasm, nucleus, and endolysosomal pathway as compared to the extracellular matrix and circulation system. [29,86] Disulfide bonds are most frequently used for the development of redox responsive delivery systems as they are readily cleaved intracellularly. Cuchelkar et al, for example, prepared linear HPMA polymer conjugates in which the drug was conjugated to the polymer backbone via disulfide linker.…”

Section: Endosomes/ Lysosomesmentioning

confidence: 99%

“…[91] In addition to using the reducing intracellular environment to trigger drug release, the elevated intracellular glutathione concentration can also be exploited to induce disassembly of polymerbased carriers. [29,86] As an example, Liu et al described self-assembled micelles based on a disulfide-linked poly(methacrylic acid)-b-poly(ε-caprolactone) copolymer (PMAA-b-PCL-SS-PCL-b-PMAA), which were used for paclitaxel delivery. [92] Hubbell and co-workers prepared reduction sensitive polymersomes, which were based on PEG-SS-poly(propylene sulfide) (PEG-SS-PPS) diblock copolymers and quickly disrupted inside cells leading to fast release of the cargo.…”

Section: Endosomes/ Lysosomesmentioning

confidence: 99%

“…[94] Selenium-based compounds have also been used recently to promote carrier disassembly as a response to glutathione as well as reactive oxygen species (ROS) such as hydrogen peroxide. [86,95] For instance, Yan and co-workers designed amphiphilic hyperbranched polymers alternating hydrophobic selenide groups and hydrophilic phosphate segments in the dendritic backbone. These polymers selfassembled in water to form core-shell micelles, which could incorporate the anticancer drug doxorubicin.…”

Section: Endosomes/ Lysosomesmentioning

confidence: 99%

See 1 more Smart Citation

Controlling and Monitoring Intracellular Delivery of Anticancer Polymer Nanomedicines

Battistella

Klok

2017

Macromolecular Bioscience

View full text Add to dashboard Cite

Polymer nanomedicines are very attractive to improve the delivery of chemotherapeutics. Polymer conjugates and other polymer‐based nanocarriers allow to increase plasma half‐life and drug bioavailability and can also be guided toward tumors using passive and active targeting strategies. Since many chemotherapeutics act on targets that are located in well‐defined subcellular compartments, other important factors that contribute to an efficient therapy include cellular internalization and subsequent intracellular trafficking of the polymer nanomedicines and/or its payload to the appropriate organelle in the cytoplasm. This article provides an overview of the different approaches that have been developed to control intracellular delivery of polymer nanomedicines and discusses the different techniques that can be used to monitor these processes.

show abstract

Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery

Cited by 1,232 publications

References 106 publications

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

Intracellularly Degradable, Self‐Assembled Amphiphilic Block Copolycurcumin Nanoparticles for Efficient In Vivo Cancer Chemotherapy

Controlling and Monitoring Intracellular Delivery of Anticancer Polymer Nanomedicines

Contact Info

Product

Resources

About