Combination Therapy using Co-encapsulated Resveratrol and Paclitaxel in Liposomes for Drug Resistance Reversal in Breast Cancer Cells in vivo

Meng, Jie; Guo, Fangqin; Xu, Haiyan; Liang, Wei; Wang, Chen; Yang, Xiao

doi:10.1038/srep22390

Cited by 165 publications

(106 citation statements)

References 38 publications

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“…8). It is noteworthy that the PTX@NP-pD-Al group the amount of PTX accumulated in the tumor (3.4 ± 1.2%ID/g) was similar to that in the liver (3.2 ± 2.0%ID/g), because NPs (including PTX@NPxAl) typically exhibit relatively high accumulation in the liver at 24 h post-treatment [78]. The PTX contents in the kidneys and the lungs were below the detection limit, suggesting minimal accumulation of both NPs in these organs.…”

Section: Resultsmentioning

confidence: 99%

Surface modification of polymer nanoparticles with native albumin for enhancing drug delivery to solid tumors

et al. 2018

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Albumin is a promising surface modifier of nanoparticulate drug delivery systems. Serving as a dysopsonin, albumin can protect circulating nanoparticles (NPs) from the recognition and clearance by the mononuclear phagocytic system (MPS). Albumin may also help transport the NPs to solid tumors based on the increased consumption by cancer cells and interactions with the tumor microenvironment. Several studies have explored the benefits of surface-bound albumin to enhance NP delivery to tumors. However, it remains unknown how the surface modification process affects the conformation of albumin and the performance of the albumin-modified NPs. We use three different surface modification methods including two prevalent approaches (physisorption and interfacial embedding) and a new method based on dopamine polymerization to modify the surface of poly(lactic-co-glycolic acid) NPs with albumin and compare the extent of albumin binding, conformation of the surface-bound albumin, and biological performances of the albumin-coated NPs. We find that the dopamine polymerization method preserves the albumin structure, forming a surface layer that facilitates NP transport and drug delivery into tumors via the interaction with albumin-binding proteins. In contrast, the interfacial embedding method creates NPs with denatured albumin that offers no particular benefit to the interaction with cancer cells but rather promotes the MPS uptake via direct and indirect interactions with scavenger receptor A. This study demonstrates that the surface-bound albumin can bring distinct effects according to the way they interact with NP surface and thus needs to be controlled in order to achieve favorable therapeutic outcomes.

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Section: Resultsmentioning

confidence: 99%

Surface modification of polymer nanoparticles with native albumin for enhancing drug delivery to solid tumors

et al. 2018

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“…Due to differences in the pharmacokinetics of the combined drugs, it’s therapy remains unsatisfactory. Nevertheless, a promising approach to circumvent the drug efflux system and improve the effects of the drug combination is the use of a nanocarrier to deliver the drugs to the targets in cancer cells [30]. We recently reported the resveratrol-docetaxel combined modulatory effects on several apoptosis-related proteins in PCa [15].…”

Section: Discussionmentioning

confidence: 99%

“…Resveratrol (3,4,5-trihydroxystilbene), a polyphenolic phytoalexin commonly available through several plant sources has been shown to possess antitumor effects by inducing apoptosis, cell cycle arrest, and the suppression of certain transcription factors in cancer cells [30]. Moreover, RES was found to be a promising chemopreventive molecule due to its antioxidant, anti-inflammatory and growth inhibitory effects [31].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, RES was found to be a promising chemopreventive molecule due to its antioxidant, anti-inflammatory and growth inhibitory effects [31]. Thus, combining RES with other drugs such as DTX can be advantageous by reducing its cytotoxicity (of DTX) without additional side effects in vivo [30]. However, the efficacy and appropriateness of RES remained inconsistent because of its bioavailability due to quick absorption and metabolism in the in vivo system [32].…”

Section: Discussionmentioning

confidence: 99%

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Reversal of drug resistance by planetary ball milled (PBM) nanoparticle loaded with resveratrol and docetaxel in prostate cancer

2018

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The folate receptor (FR) is a valued target that is highly expressed in various cancers, which will expedite the development of ligand-receptor binding based cancer therapeutics. In the present investigation, through tissue microarray analysis, we report higher levels of folate receptor expression in prostate cancer (PCa) tissue derived from patients, which were minimal in normal tissue. For folate-receptor based targeted therapy of PCa, we generated novel planetary ball milled (PBM) nanoparticles (NPs) encapsulated with resveratrol (RES), and in combination with docetaxel (DTX) and conjugated with folic acid (FA) on the surface. The cytotoxic effect of FA-conjugated DTX-nanoparticles was found effectual that reduced the concentration of free drug (DTX) to 28 times. Flow cytometry analysis showed a significant increase in the number of apoptotic cells by 30.92% and 65.9% in the FA-conjugated RES and in combination with DTX nanoparticle formulation respectively. However, only 8.9% apoptotic cells were found with control (empty NP). The expressions of NF-kB p65, COX-2, pro (BAX, BAK) and anti-apoptotic (BCL-2, BCL-XL) genes were significantly reduced after treatment with FA-RES + DTX-NP. In addition, the FA-conjugated DTX formulation exhibited additional cytotoxic effects with the down-regulation of survivin and an increased expression of Cleaved Caspase-3 in PCa cells. Further, we observed that treating DTX resistant PCa cells with FA-RES + DTX-NP exhibited a reversal of the ABC-transporter markers thereby limiting the multidrug resistance phenotype of the cancer cells. Our results strongly suggested that FA conjugated nanoparticle drugs acted as effective inhibitors of drug efflux that effectually enhances the intracellular concentration of the drug to exhibit their cytotoxic effect.

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“…This property of POEGMA-PDPA vesicles renders them well suited for cellular cargo delivery: following cellular internalization, the polymersomes disassemble at endosomal acidic pH followed by endosomal rupture and release of cargo in the cytosol [29–31]. Thick and robust hydrophobic polymersome membrane is less leaky than lipid bilayer of liposomes [32]. We have demonstrated that the POEGMA-PDPA polymersomes retain the drug inside for several weeks at neutral pH and quickly release the cargo at mildly acidic pH [27].…”

Section: Introductionmentioning

confidence: 99%

iRGD peptide conjugation potentiates intraperitoneal tumor delivery of paclitaxel with polymersomes

et al. 2016

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Polymersomes are versatile nanoscale vesicles that can be used for cytoplasmic delivery of payloads. Recently, we demonstrated that pH-sensitive polymersomes exhibit an intrinsic selectivity towards intraperitoneal tumor lesions. A tumor homing peptide, iRGD, harbors a cryptic C-end Rule (CendR) motif that is responsible for neuropilin-1 (NRP-1) binding and for triggering extravasation and tumor penetration of the peptide. iRGD functionalization increases tumor selectivity and therapeutic efficacy of systemic drug-loaded nanoparticles in many tumor models. Here we studied whether intraperitoneally administered paclitaxel-loaded iRGD-polymersomes show improved efficacy in the treatment of peritoneal carcinomatosis. First, we demonstrated that the pH-sensitive polymersomes functionalized with RPARPAR (a prototypic CendR peptide) or iRGD internalize in the cells that express NRP-1, and that internalized polymersomes release their cargo inside the cytosol. CendR-targeted polymersomes loaded with paclitaxel were more cytotoxic on NRP-1-positive cells than on NRP-1-negative cells. In mice bearing peritoneal tumors of gastric (MKN-45P) or colon (CT26) origin, intraperitoneally administered RPARPAR and iRGD-polymersomes showed higher tumor-selective accumulation and penetration than untargeted polymersomes. Finally, iRGD-polymersomes loaded with paclitaxel showed improved efficacy in peritoneal tumor growth inhibition and in suppression of local dissemination compared to the pristine paclitaxel-polymersomes or Abraxane. Our study demonstrates that iRGD-functionalization improves efficacy of paclitaxel-polymersomes for intraperitoneal treatment of peritoneal carcinomatosis.

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Combination Therapy using Co-encapsulated Resveratrol and Paclitaxel in Liposomes for Drug Resistance Reversal in Breast Cancer Cells in vivo

Cited by 165 publications

References 38 publications

Surface modification of polymer nanoparticles with native albumin for enhancing drug delivery to solid tumors

Surface modification of polymer nanoparticles with native albumin for enhancing drug delivery to solid tumors

Reversal of drug resistance by planetary ball milled (PBM) nanoparticle loaded with resveratrol and docetaxel in prostate cancer

iRGD peptide conjugation potentiates intraperitoneal tumor delivery of paclitaxel with polymersomes

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