Dual-responsive nanoparticles based on oxidized pullulan and a disulfide-containing poly(β-amino) ester for efficient delivery of genes and chemotherapeutic agents targeting hepatoma

Wang, Hemei; Wan, Guoyun; Liu, Yuanyuan; Chen, Bo-Wei; Chen, Hongli; Zhang, Sipei; Wang, Dan; Xiong, Qingqing; Zhang, Ning; Wang, Yinsong

doi:10.1039/c6py01664b

Cited by 35 publications

(26 citation statements)

References 39 publications

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“…HPPDC nanoparticles consisted of hydrophilic HA shells and hydrophobic PPDC nanocores co-loaded with a chemotherapeutic drug DOX and a COX-2 selective inhibitor CXB. Our previous investigations have shown that ssPBAE has significant amphiphilic property and can self-assemble to form nanoparticles for efficiently loading genes and/or anticancer drugs [28, 29]. Firstly, ssPBAE was synthesized and chemically characterized by 1 H NMR spectrum (Additional file 1: Fig.…”

Section: Resultsmentioning

confidence: 99%

“…ssPBAE was synthesized by ourselves according to the previous report [28, 29] and the polymerization degree detected by the 1 H NMR method was about 12. HA with a molecular mass of 33 kDa was purchased from Bloomage Freda Biopharm (Jinan, China).…”

Section: Methodsmentioning

confidence: 99%

“…In this study, we designed an intelligent nanoparticle system based on disulfide-containing poly(β-amino ester) (ssPBAE) for the co-loading, targeted delivery and controlled release of DOX and CXB. ssPBAE is a novel cationic polymer possessing pH and redox dual sensitivities due to the presence of both tertiary amine group and disulfide bond in its monomer structure and we have successfully used it as a carrier material for intracellular delivery of genes and anticancer drugs [28, 29]. Here ssPBAE is firstly complexed with poly(lactic-co-glycolic acid) (PLGA) to prepare hydrophobic nanocores containing DOX and CXB (PPDC nanocores), and then hyaluronic acid (HA) coats on these nanocores through charge interactions to form “core–shell” structured HPPDC nanoparticles (Fig.…”

Section: Introductionmentioning

confidence: 99%

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pH and redox dual-responsive nanoparticles based on disulfide-containing poly(β-amino ester) for combining chemotherapy and COX-2 inhibitor to overcome drug resistance in breast cancer

et al. 2019

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Background Multidrug resistance (MDR) generally leads to breast cancer treatment failure. The most common mechanism of MDR is the overexpression of ATP-binding cassette (ABC) efflux transporters such as P-glycoprotein (P-gp) that reduce the intracellular accumulation of various chemotherapeutic agents. Celecoxib (CXB), a selective COX-2 inhibitor, can dramatically enhance the cytotoxicity of doxorubicin (DOX) in breast cancer cells overexpressing P-gp. Thus it can be seen that the combination of DOX and CXB maybe obtain synergistic effects against breast cancer by overcoming drug resistance. Results In this study, we designed a pH and redox dual-responsive nanocarrier system to combine synergistic effects of DOX and CXB against drug resistant breast cancer. This nanocarrier system denoted as HPPDC nanoparticles showed good in vitro stability and significantly accelerated drug releases under the acidic and redox conditions. In drug-resistant human breast cancer MCF-7/ADR cells, HPPDC nanoparticles significantly enhanced the cellular uptake of DOX through the endocytosis mediated by CD44/HA specific binding and the down-regulated P-gp expression induced by COX-2 inhibition, and thus notably increased the cytotoxicity and apoptosis-inducing activity of DOX. In MCF-7/ADR tumor-bearing nude mice, HPPDC nanoparticles showed excellent tumor-targeting ability, remarkably enhanced tumor chemosensitivity and reduced COX-2 and P-gp expressions in tumor tissues. Conclusion All results demonstrated that HPPDC nanoparticles can efficiently overcome drug resistance in breast cancer both in vitro and in vivo by combining chemotherapy and COX-2 inhibitor. In a summary, HPPDC nanoparticles show a great potential for combination treatment of drug resistant breast cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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pH and redox dual-responsive nanoparticles based on disulfide-containing poly(β-amino ester) for combining chemotherapy and COX-2 inhibitor to overcome drug resistance in breast cancer

et al. 2019

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“…Only the salicylamide-modified PEI was a reliable carrier for mRNA delivery in HeLa and U87 cells [104]. As an alternative to PEI, poly (β-amino esters) (PBAEs) exhibit several advantages, such as easy synthesis, relatively low cytotoxicity, and good degradability, and have been demonstrated as an effective delivery system for nucleic acids [105, 106]. However, serum instability may be one of the drawbacks of PBAEs for systemic administration.…”

Section: Nanotechnology Platforms For Mrna Deliverymentioning

confidence: 99%

Biomedical applications of mRNA nanomedicine

et al. 2018

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As an attractive alternative to plasmid DNA, messenger RNA (mRNA) has recently emerged as a promising class of nucleic acid therapeutics for biomedical applications. Advances in addressing the inherent shortcomings of mRNA and in the development of nanoparticle-based delivery systems have prompted the development and clinical translation of mRNA-based medicines. In this review, we discuss the chemical modification strategies of mRNA to improve its stability, minimize immune responses, and enhance translational efficacy. We also highlight recent progress in nanoparticle-based mRNA delivery. Considerable attention is given to the increasingly widespread applications of mRNA nanomedicine in the biomedical fields of vaccination, protein-replacement therapy, gene editing, and cellular reprogramming and engineering.

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“…These findings further confirmed the specific affinity of Au@Pul-2 for hepatoma cells. In addition, the internalization of Au@Pul-2 was believed to undergo receptormediated endocytosis through binding with overexpressed ASGPR 48 .…”

Section: Cellular Internalization Of the Au@psa Nanocompositesmentioning

confidence: 99%

Self-destructible polysaccharide nanocomposites with unlockable Au nanorods for high-performance photothermal therapy

et al. 2018

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Multifunctional organic/inorganic nanocomposites are highly attractive for effective biomedical applications. In this work, versatile types of self-destructible polysaccharide (dextran or pullulan) nanocomposites (denoted Au@PSa) with adjustable amounts of unlockable Au nanorods (Au NRs) were fabricated as highly efficient photothermal cancer therapy systems. Taking advantage of the acidic endosomes and high concentration of glutathione (GSH) present in cancer cells, the responsive self-destruction of Au@PSa nanocomposites could unlock the abundant encapsulated Au NRs within cells. Notably, the pullulan-based nanocomposites (denoted Au@Pul) demonstrated liver cell-targeting properties, which could enhance the therapeutic effects while minimizing side effects. The strong absorption of the unlocked Au NRs in the near-infrared region was utilized to examine the photothermal performance. The Au@PSa nanocomposites with a moderate amount of Au NRs in the matrix exhibited very impressive photothermal effects in tumor therapy, where the encapsulated Au NRs were unlocked in the tumor region to realize the observed high performance. The proposed system could be further extended, as the polysaccharides were functionalized with amino groups. The current work provides a facile strategy to construct flexible therapeutic platforms with responsive selfdestruction features.

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Dual-responsive nanoparticles based on oxidized pullulan and a disulfide-containing poly(β-amino) ester for efficient delivery of genes and chemotherapeutic agents targeting hepatoma

Abstract: A dual-responsive nanoparticle system was designed for the efficient delivery of genes and chemotherapeutic agents through polymer degradation responding orderly to the tumor intracellular pH and redox state.

Cited by 35 publications

References 39 publications

pH and redox dual-responsive nanoparticles based on disulfide-containing poly(β-amino ester) for combining chemotherapy and COX-2 inhibitor to overcome drug resistance in breast cancer

pH and redox dual-responsive nanoparticles based on disulfide-containing poly(β-amino ester) for combining chemotherapy and COX-2 inhibitor to overcome drug resistance in breast cancer

Biomedical applications of mRNA nanomedicine

Self-destructible polysaccharide nanocomposites with unlockable Au nanorods for high-performance photothermal therapy

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