Dual endogenous stimuli-responsive polyplex micelles as smart two-step delivery nanocarriers for deep tumor tissue penetration and combating drug resistance of cisplatin

Li, Junjie; Ye, Han; Chen, Qixian; Shi, Hongdong; Rehman, Saif ur; Siddiq, Muhammad; Ge, Zhishen; Liu, Shiyong

doi:10.1039/c3tb21383h

Cited by 60 publications

(40 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various pH-responsive nanomedicines have been developed for efficient drug delivery. 22 Furthermore, dual stimuli responsive nanomedicines in response to an internal or external stimulus, such as dual pH, 23,24 reduction/pH, 25,26 enzyme/ temperature, 27 light/pH, 28,29 were developed.…”

Section: Introductionmentioning

confidence: 99%

Dual temperature- and pH-responsive polymeric micelle for selective and efficient two-step doxorubicin delivery

et al. 2017

View full text Add to dashboard Cite

We report a polymeric micelle drug delivery system, which enables selective intracellular uptake with external thermal stimulation, and effective release of a drug at internal acidic endosomal pH. We developed a dual temperature-and pH-responsive polymeric micelle composed of a temperatureresponsive corona segment with poly(N-isopropylacrylamide-co-dimethylacrylamide) [P(NIPAAm-coDMAAm)] and a pH-responsive core segment with poly[2-(diisopropylamino)ethyl methacrylate] (PDPA).A dual temperature-and pH-responsive amphiphilic diblock copolymer was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. The dithiobenzoate end-group was removed with radical-induced ester exchange. This copolymer formed nano-sized micelles in aqueous solution, and encapsulated anti-cancer agent, doxorubicin (DOX). The resultant micelles exhibited a temperature-dependent phase transition at a temperature slightly higher than body temperature, and intracellular uptake of encapsulated DOX was accelerated above the phase transition temperature. A transition from neutral to positive charge, leading to micelle disassembly, accelerated the release of Nile red as a model drug. The cytotoxicity of doxorubicin (DOX)-loaded dual temperature-and pHresponsive micelles against human cervical cancer HeLa cells was significantly greater at 42 C than at 37 C, while no significant temperature-dependent cytotoxicity was observed with DOX-loaded micelles that were only temperature-responsive. This proof-of-concept synergistic two-step delivery system with enhanced intracellular uptake upon external thermal stimulation and rapid release of DOX at internal acidic endosomal pH was effective against tumor cells in vitro.

show abstract

Section: Introductionmentioning

confidence: 99%

Dual temperature- and pH-responsive polymeric micelle for selective and efficient two-step doxorubicin delivery

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Positively charged nanoparticles possess higher affinity with the negatively charged cell membrane, which facilitates cellular uptake, whereas their severe cytotoxicity, strong interactions with blood components, and rapid clearance often impede the in vivo applications. [16][17][18] The generated amide bond is cleavable under mildly acidic conditions but is stable at neutral or basic pH, 19 whereas the DMMA-decorated nanoparticles are inert under physiological conditions. [11][12][13][14][15] Reactions of 2,3-dimethylmaleic anhydride (DMMA) and amino groups on the particle surface have been used to shield the positive charge of nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

Multi-stage, charge conversional, stimuli-responsive nanogels for therapeutic protein delivery

Zhang

Haag

2015

Biomater. Sci.

View full text Add to dashboard Cite

A boronate ester crosslinked zwitterionic nanogel (NGCA) with ATP/pH-sensitivity has been developed with an inverse nanoprecipitation technique to achieve a two-stage charge conversion that responds to tumor extracellular conditions (pH 6.5-6.8) and an intracellular acidic environment (pH 5-6). Cationic cytochrome C (CC), a therapeutic protein, has been encapsulated into NGCA through inverse nanoprecipitation via electrostatic interactions to form protein-loaded nanogel (NGCA-CC). By adjusting the ratio of the amino and carboxyl groups in the nanogels, negatively charged nanogels that are safer under physiological conditions (pH 7.4) can convert their surface charge to positive at tumor extracellular pH, which enhance their cellular uptake efficiency. The citraconic amide formed from citraconic anhydride and amine can be cleaved in the intracellular acidic organelles to expose more amino groups and facilitate endosomal escape. The release of CC is accelerated in the presence of 5 mM ATP or under acidic conditions. Confocal laser scanning microscopy (CLSM) and flow cytometry have shown that NGCA-CC's cell uptake is higher at pH 6.5 than at pH 7.4. MTT and real-time cell analysis (RTCA) have illustrated that there is more toxicity at pH 6.5 than at pH 7.4. The apoptosis process induced by CC was determined by flow cytometry.

show abstract

“…The cations or ligands on the surface of nanocarriers are proved to induce enhanced cell internalization. [57][58][59] When the nanocarriers accumulate at the tumor site, the small molecules are removed, which is triggered by both internal and external stimuli. 4,56 Therefore, small molecule cage is used as a usual approach to shield the cations or ligands.…”

Section: Nanoparticle Reengineering Mediated By Uncaging Small Moleculesmentioning

confidence: 99%

Emerging antitumor applications of extracellularly reengineered polymeric nanocarriers

et al. 2015

View full text Add to dashboard Cite

Recently, polymeric nanocarriers with shielding surfaces, e.g., poly(ethylene glycol) and small molecules, have been widely applied in antitumor drug delivery mainly because of their stealth during blood circulation. However, the shielding shell greatly hinders the tumor penetration, drug release, and cell internalization of the nanocarriers, which leads to unsatisfactory therapeutic efficacy. To integrate the extended blood circulation time and the enhanced drug transmission in one platform, some extracellularly stimuli-mediated shell-sheddable polymeric nanocarriers have been exploited. The systems are stealthy and stable during blood circulation, and as soon as they reach tumor tissue, the shielding matrices are removed, which is triggered by extracellular endogenous stimuli (e.g., pH or enzymes) or exogenous excitations (e.g., light or voltage). This review mainly focuses on recent advances in the designs and emerging antitumor applications of extracellularly reengineered polymeric nanocarriers for directional drug delivery, as well as perspectives for future developments.

show abstract

Dual endogenous stimuli-responsive polyplex micelles as smart two-step delivery nanocarriers for deep tumor tissue penetration and combating drug resistance of cisplatin

Abstract: Polyplex micelles were constructed for deep tumor tissue penetration and combating drug resistance via endogenous stimuli-responsive two-step release profiles.

Cited by 60 publications

References 56 publications

Dual temperature- and pH-responsive polymeric micelle for selective and efficient two-step doxorubicin delivery

Dual temperature- and pH-responsive polymeric micelle for selective and efficient two-step doxorubicin delivery

Multi-stage, charge conversional, stimuli-responsive nanogels for therapeutic protein delivery

Emerging antitumor applications of extracellularly reengineered polymeric nanocarriers

Contact Info

Product

Resources

About