Trigger responsive polymeric nanocarriers for cancer therapy

Kaur, Swaran; Prasad, Chandrashekhar; Balakrishnan, Biji; Banerjee, Rinti

doi:10.1039/c5bm00002e

Cited by 121 publications

(59 citation statements)

References 255 publications

(393 reference statements)

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“…2, 5, 14-16 35 Intrinsic stimuli in tumor cells, such as acidic pH, the presence of specific enzymes and redox potential, can be used to ensure successful release of therapeutic agents on the tumor site in a spatially controlled manner. [17][18][19][20][21][22][23][24] In particular, redox and pH dual-responsive DDSs were paid more attention because of the 40 existence of redox potential and pH gradient between the extraand intracellular space. [25][26][27][28][29][30][31][32][33][34] Inside the body, glutathione (GSH), a natural reducing agent for disulfide bonds, was found in the blood plasma at µM levels (approximately ~2 µM), due to rapid enzymatic degradation, whereas a substantially high 45 concentration at mM levels (2-10 mM) was found in the cytoplasm of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Folate-decorated redox/pH dual-responsive degradable prodrug micelles for tumor triggered targeted drug delivery

2016

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To address the obstacles facing the clinical use of paclitaxel, including poor water solubility, side effects and lack of tumor selectivity, a novel folate-decorated and redox and pH dual-responsive micellar drug delivery system was developed based on folate-poly(ethylene 10 glycol)-b-poly((α-paclitaxel-SS-caprolactone)-co-caprolactone) (e.i, FA-PEG-b-P((PTX-SS-CL)-co-CL) conjugates with thiol and acidcleavable linkages. The paclitaxel (PTX) conjugated amphiphilic block copolymer prodrug was self-assembled in phosphate buffer (pH 7.4, 0.1 M) into nanosized spherical micelles (~ 96.5 nm). In vitro release studies demonstrated that the prodrug micelles are relatively stable at normal physiologic conditions but susceptible to tumor-relevant reductive and acidic conditions which would trigger the release of chemically loaded drugs. Notably, folate-decorated PTX prodrug micelles based on FA-PEG-b-P((PTX-SS-CL)-co-CL) conjugates 15 displayed apparent targetability to folate receptor-overexpressing HeLa cells. MTT assays showed that the therapeutic efficacy of these micelles against HeLa cancer cells (IC 50 = 0.75 µg mL -1 ) was enhanced compared with free PTX (IC 50 = 0.87 µg mL -1 ). These results suggest that FA-PEG-b-P((PTX-SS-CL)-co-CL) conjugates may offer a promising strategy for PTX delivery in the treatment of various tumors, with enhanced efficacy and fewer adverse effects. 20

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Section: Introductionmentioning

confidence: 99%

Folate-decorated redox/pH dual-responsive degradable prodrug micelles for tumor triggered targeted drug delivery

2016

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“…[1][2][3][4][5][6][7][8][9][10] These polymers can undergo the reversible changes in response to the external stimuli such as temperature, pH, redox, light, salt, sugar, and carbon dioxide. [1][2][3][4][5][6][7][8][9][10] These polymers can undergo the reversible changes in response to the external stimuli such as temperature, pH, redox, light, salt, sugar, and carbon dioxide.…”

Section: Introductionmentioning

confidence: 99%

A star-shaped amphiphilic block copolymer with dual responses: synthesis, crystallization, self-assembly, redox and LCST–UCST thermoresponsive transition

2016

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synthesized by the combination of ring-opening polymerization (ROP), dicyclohexylcarbodiimide (DCC) reaction and atom transfer radical polymerization (ATRP). After the quaternization reaction of the PDMAEMA segment with excess 1,3propane sultone, poly(ε-caprolactone)-SS-poly(3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate (SPCL-SS-PDMAPS) was obtained. The star-shaped structure of the copolymers and the presence of the amorphous PDMAEMA and PDMAPS in copolymers decreased or even completely suppressed the crystallizability of PCL in copolymers. These copolymers could self-assemble into spherical micelles in water. The thermoresponsive micelle solutions showed transition from a lower critical solution temperature (LCST) of SPCL-SS-PDMAEMA to an upper critical solution temperature (UCST) of SPCL-SS-PDMAPS, indicating that the LCST-UCST transition of the micellar solutions can be accomplished by the transition of PDMAEMA to PDMAPS. Moreover, the redox-responsive investigation showed that the distributions of hydrodynamic radius (Rh) broadened with the emergence of aggregates when DL-dithiothreitol (DTT) was added into the micellar systems, since the DTT would cause the breakage of disulfide bonds linking PCL and the PDMAEMA/PDMAPS blocks in copolymers.The micelles/aggregates that were self-assembled from star-shaped copolymer presented redox-responsive behaviour and LCST-UCST thermoresponsive transition.

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“…To manage efficient drug delivery to the target site, various strategies have been developed in the second-generation polymeric nanoparticles by incorporating stimuli-responsive properties (e.g., pH, temperature, or light activation). Third-generation polymeric nanocarriers are represented by multi-functionalities, such as targeting and multi-drug release properties [70]. In this section, we discuss four main types of polymeric nanomaterials: polymer-drug conjugates, micelles, nanogels, and dendrimers.…”

Section: Polymeric Nanomaterialsmentioning

confidence: 99%

Evolution and clinical translation of drug delivery nanomaterials

et al. 2017

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With the advent of technology, the role of nanomaterials in medicine has grown exponentially in the last few decades. The main advantage of such materials has been exploited in drug delivery applications, due to their effective targeting that in turn reduces systemic toxicity compared to the conventional routes of drug administration. Even though these materials offer broad flexibility based on targeting tissue, disease, and drug payload, the demand for more effective yet highly biocompatible nanomaterial-based drugs is increasing. While therapeutically improved and safe materials have been introduced in nanomedicine platforms, issues related to their degradation rates and bio-distribution still exist, thus making their successful translation for human use very challenging. Researchers are constantly improving upon novel nanomaterials that are safer and more effective not only as therapeutic agents but as diagnostic tools as well, making the research in the field of nanomedicine ever more fascinating. In this review stress has been made on the evolution of nanomaterials that have been approved for clinical applications by the United States Food and Drug Administration Agency (FDA).

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Trigger responsive polymeric nanocarriers for cancer therapy

Cited by 121 publications

References 255 publications

Folate-decorated redox/pH dual-responsive degradable prodrug micelles for tumor triggered targeted drug delivery

Folate-decorated redox/pH dual-responsive degradable prodrug micelles for tumor triggered targeted drug delivery

A star-shaped amphiphilic block copolymer with dual responses: synthesis, crystallization, self-assembly, redox and LCST–UCST thermoresponsive transition

Evolution and clinical translation of drug delivery nanomaterials

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