pH sensitive polyelectrolyte complex micelles for highly effective combination chemotherapy

Ramasamy, Thiruganesh; Kim, Jeong Hwan; Choi, Jae Young; Tran, Tuan Hiep; Choi, Han‐Gon; Yong, Chul Soon; Kim, Jong Oh

doi:10.1039/c4tb00867g

Cited by 80 publications

(61 citation statements)

References 23 publications

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“…[4][5][6] In this case, stimuli-responsive polymers provide a solid platform for constructing different cocktail drugs loaded nanomedicines (e.g., hydrophobic and hydrophilic drugs), which exhibit "on-demand" drug release profiles and combination cytotoxicity. [7][8][9] Therefore polymeric nanotechnology might further enhance antitumor efficacy of cocktail chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Plasmonic, Targeted, and Dual Drugs-Loaded Polypeptide Composite Nanoparticles for Synergistic Cocktail Chemotherapy with Photothermal Therapy

Zhou

et al. 2016

Biomacromolecules

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To integrate cocktail chemotherapy with photothermal therapy into one biocompatible and biodegradable nanocarrier, the plasmonic, lactose-targeted, and dual anticancer drugs-loaded polypeptide composite nanoparticles were for the first time fabricated under mild conditions. The glyco-PEGylated polypeptide micelles that self-assembled from the lactose (LAC) and PEG grafted polycysteine terpolymer were used as templates to generate the plasmonic composite nanoparticles, as mainly characterized by DLS, TEM, SEM, and XPS. These composite nanoparticles showed a broad and strong near-infrared (NIR) absorption at 650-1100 nm and increased the temperature of phosphate buffer solution by 30.1 °C upon a continuous-wave laser irradiation (808 nm, 5 min, 2 W·cm(-2)), while the same dose of NIR-mediated heating completely killed HepG2 cancer cells in vitro, presenting excellent photothermal properties. Two anticancer drugs, doxorubicin (DOX) and 6-mercaptopurine (6-MP), were loaded into the composite nanoparticles through physical interactions and Au-S bond, respectively. The dual drugs-loaded composite nanoparticles exhibited reduction-sensitive and NIR-triggered cocktail drugs release profiles and trigger-enhanced cytotoxicity. As evidenced by flow cytometry, fluorescence microscopy, and MTT assay, the LAC-coated composite nanoparticles were more internalized by the HepG2 than the HeLa cell line, demonstrating a LAC-targeting enhanced cytotoxicity toward HepG2. The combination cocktail chemo-photothermal therapy produced a lower half maximal inhibitory concentration than cocktail chemotherapy or photothermal therapy alone, displaying a good synergistic antitumor effect.

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Section: Introductionmentioning

confidence: 99%

Plasmonic, Targeted, and Dual Drugs-Loaded Polypeptide Composite Nanoparticles for Synergistic Cocktail Chemotherapy with Photothermal Therapy

Zhou

et al. 2016

Biomacromolecules

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“…[6][7][8][9] Some co-delivery nanoparticles (NPs) have been established to load two small-molecule anticancer drugs, for example, pirarubicin and paclitaxel, 10 doxorubicin (DOX) and paclitaxel, 11 or cisplatin and rapamycin, 12 or a small-molecule drug plus a macromolecule anticancer drug, such as, protein, 13 miRNA, 14 DNA, 15 or gene agents. 5 Co-NDDS synergistically inhibited the growth of the tumor compared with free drugs.…”

Section: Introductionmentioning

confidence: 99%

Co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance

Zhang

Kong

Jie

et al. 2017

IJN

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Combination chemotherapy in clinical practice has been generally accepted as a feasible strategy for overcoming multidrug resistance (MDR). Here, we designed and successfully prepared a co-delivery system named S-D1@L-D2 NPs, where denoted some smaller nanoparticles (NPs) carrying a drug doxorubicin (DOX) were loaded into a larger NP containing another drug (vincristine [VCR]) via water-in-oil-in-water double-emulsion solvent diffusion-evaporation method. Chitosan-alginate nanoparticles carrying DOX (CS-ALG-DOX NPs) with a smaller diameter of about 20 nm formed S-D1 NPs; vitamin E D-α-tocopheryl polyethylene glycol 1000 succinate-modified poly(lactic-co-glycolic acid) nanoparticles carrying VCR (TPGS-PLGA-VCR NPs) with a larger diameter of about 200 nm constituted L-D2 NPs. Some CS-ALG-DOX NPs loaded into TPGS-PLGA-VCR NPs formed CS-ALG-DOX@TPGS-PLGA-VCR NPs. Under the acidic environment of cytosol and endosome or lysosome in MDR cell, CS-ALG-DOX@TPGS-PLGA-VCR NPs released VCR and CS-ALG-DOX NPs. VCR could arrest cell cycles at metaphase by inhibiting microtubule polymerization in the cytoplasm. After CS-ALG-DOX NPs escaped from endosome, they entered the nucleus through the nuclear pore and released DOX in the intra-nuclear alkaline environment, which interacted with DNA to stop the replication of MDR cells. These results indicated that S-D1@L-D2 NPs was a co-delivery system of intracellular precision release loaded drugs with pH-sensitive characteristics. S-D1@L-D2 NPs could obviously enhance the in vitro cytotoxicity and the in vivo anticancer efficiency of co-delivery drugs, while reducing their adverse effects. Overall, S-D1@L-D2 NPs can be considered an innovative platform for the co-delivery drugs of clinical combination chemotherapy for the treatment of MDR tumor.

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“…This observation indicated that the drug-related toxicity could be overcome when the drugs were encapsulated into LPH nanoparticles. 19 The results of histomorphometrical analysis are shown in Table 3, and the representative histological-immunohistochemical profiles of tumor masses are shown in Figure 8C and D. The tumor cell volumes in DTX-and DTX-LPH-treated tumor masses were reduced by 35.2% and 62.3%, respectively. The percentage of caspase-3-immunolabeled cells in DTX-and DTX-LPH-treated tumor masses increased by 214.5% and 412.6%, and the percentage of PARP-positive cells increased by 212.6% and 371.7%, compared with untreated control, respectively.…”

Section: In Vivo Antitumor Efficacymentioning

confidence: 96%

“…At the end of the experiment, the animals were sacrificed and the tumor masses harvested, weighed, photographed, and stored in formalin 10% for further studies. 19 The protocols for the animal studies were approved by the Institutional Animal Ethical Committee, Yeungnam University, South Korea.…”

Section: Establishment Of In Vivo Antitumor Activity In Vivo Antitumomentioning

confidence: 99%

Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells

Kim¹,

Tran²,

Ramasamy³

et al. 2015

IJN

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The attachment of polyethylene glycol (PEG) increases the circulation time of drug-containing nanoparticles; however, this also negatively affects cellular uptake. To overcome this problem, unique lipid polymer hybrid (LPH) nanoparticles were developed with a pH-responsive PEG layer that detached prior to cell uptake. Docetaxel (DTX) was incorporated into the lipid core of the nanoparticles, which was then shielded with the pH-responsive block co-polymer polyethylene glycol- b -polyaspartic acid (PEG- b -PAsp) using a modified emulsion method. The optimized LPH nanoparticles were ~200 nm and had a narrow size distribution. Drug release from DTX-loaded LPH (DTX-LPH) nanoparticles was pH-sensitive, which is beneficial for tumor targeting. More importantly, DTX-LPH nanoparticles were able to effectively induce apoptosis in cancer cells. The negative surface charge and PEG shell of vehicle remarkably enhanced the blood circulation and physiological activity of DTX-LPH nanoparticles compared with that of free DTX. The nanoparticles were also found to reduce the size of tumors in tumor-bearing xenograft mice. The in vivo anticancer effect of DTX-LPH nanoparticles was further confirmed by the elevated levels of caspase-3 and poly ADP ribose polymerase found in the tumors after treatment. Thus, the results suggest that this novel LPH system could be an effective new treatment for cancer.

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pH sensitive polyelectrolyte complex micelles for highly effective combination chemotherapy

Cited by 80 publications

References 23 publications

Plasmonic, Targeted, and Dual Drugs-Loaded Polypeptide Composite Nanoparticles for Synergistic Cocktail Chemotherapy with Photothermal Therapy

Plasmonic, Targeted, and Dual Drugs-Loaded Polypeptide Composite Nanoparticles for Synergistic Cocktail Chemotherapy with Photothermal Therapy

Co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance

Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells

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