Mulberry-like dual-drug complicated nanocarriers assembled with apogossypolone amphiphilic starch micelles and doxorubicin hyaluronic acid nanoparticles for tumor combination and targeted therapy

Li, Ké; Liu, Hao; Gao, Wei; Mu, Chunlai; Zeng, Yun; Liu, Jiajun; Xu, Liang; Wu, Daocheng

doi:10.1016/j.biomaterials.2014.10.073

Cited by 84 publications

(60 citation statements)

References 48 publications

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“…Many reports have proved that it is an efficient tool to simultaneous administration of multiple therapeutics, including cytotoxic agents, chemosensitizers, small interfering RNA (siRNA) and anti-angiogenic agents. 26 In our previous work, we have designed and synthesized PgS and CSaSt micelles. 26,34 For CSaSt micelles, we successfully encapsulated insoluble apogossypolone and soluble doxorubicin into one nanocarrier targeting hyaluronic acid receptor CD44.…”

Section: Discussionmentioning

confidence: 99%

“…26 In our previous work, we have designed and synthesized PgS and CSaSt micelles. 26,34 For CSaSt micelles, we successfully encapsulated insoluble apogossypolone and soluble doxorubicin into one nanocarrier targeting hyaluronic acid receptor CD44. Further, the EE and DL were measured; the drug-loaded NP was characterized by IR spectra, TEM and drug release assay.…”

Section: Discussionmentioning

confidence: 99%

“…26 Synthesis procedure of BSA-FA followed the literature of Meng et al 27 Briefly, 80 mg of BSA, 40 mg of EDC, 35 mg of NHS and 50 mg of FA were added to DMSO, and the mixture was stirred for 12 h in the dark at 25°C. Then, the sample was centrifuged at 10,000 rpm for 30 min to remove the excess FA and EDC/NHS.…”

Section: Synthesis Of Encapsulation Materialsmentioning

confidence: 99%

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Co-delivery nanocarriers targeting folate receptor and encapsulating 2-deoxyglucose and α-tocopheryl succinate enhance anti-tumor effect in vivo

Li¹,

Li²,

Liu³

et al. 2017

IJN

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A combination administration of chemical agents was highlighted to treat tumors. Recently, tumor cell has been found to be different from normal cell in metabolic manner. Most of cancer cells prefer aerobic glycolysis to mitochondrial oxidative phosphorylation (OXPHOS) to satisfy energy and biomass synthesis requirement to survive, grow and proliferate, which provides novel and potential therapeutic targets for chemotherapy. Here, 2-deoxy- d -glucose (2-DG), a potent inhibitor of glucose metabolism, was used to inhibit glycolysis of tumor cells; α-tocopheryl succinate (α-TOS), a water-insoluble vitamin E derivative, was chosen to suppress OXPHOS. Our data demonstrated that the combination treatment of 2-DG and α-TOS could significantly promote the anti-tumor efficiency in vitro compared with administration of the single drug. In order to maximize therapeutic activity and minimize negative side effects, a co-delivery nanocarrier targeting folate receptor (FR) was developed to encapsulate 2-DG and α-TOS simultaneously based on our previous work. Transmission electron microscope, dynamic light scattering method and UV-visible spectrophotometers were used to investigate morphology, size distribution and loading efficiency of the α-TOS-2-DG-loaded and FR-targeted nanoparticles (TDF NPs). The TDF NPs were found to possess a layer-by-layer shape, and the dynamic size was <100 nm. The final encapsulation efficiencies of α-TOS and 2-DG in TDF NPs were 94.3%±1.3% and 61.7%±7.7% with respect to drug-loading capacities of 8.9%±0.8% and 13.2%±2.6%, respectively. Almost no α-TOS release was found within 80 h, and release of 2-DG was sustained and slow within 72 h. The results of FR binding assay and fluorescence biodistribution revealed that TDF NPs could target FR highly expressed on tumor cell in vitro and in vivo. Further, in vivo anti-tumor experiments showed that TDF NPs had an improved biological function with less toxicity. Thus, our work indicates that the co-delivery TDF NPs have a great potential in tumor therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Co-delivery nanocarriers targeting folate receptor and encapsulating 2-deoxyglucose and α-tocopheryl succinate enhance anti-tumor effect in vivo

Li¹,

Li²,

Liu³

et al. 2017

IJN

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“…Recently, our group reported a mulberry-like dual-drugloaded nanomedicine following this strategy. 214 First, two perfectly matched drug-carrier pairs, apogossypolonecationic amphiphilic starch (ApoG2-CSaSt) and Dox-HA, self-assembled to form two seeds, namely, ApoG2-CSaSt micelles and Dox-HA NSs (DHA NSs), respectively. These two seeds further self-assembled to form NPs (MLDC NCs) with a mulberry-like shape and dynamic size of 83.1±6.6 nm.…”

Section: Nanomedicines Following Niche and Complex Strategiesmentioning

confidence: 99%

High drug-loading nanomedicines: progress, current status, and prospects

Shen

Liu

et al. 2017

IJN

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419

268

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Drug molecules transformed into nanoparticles or endowed with nanostructures with or without the aid of carrier materials are referred to as “nanomedicines” and can overcome some inherent drawbacks of free drugs, such as poor water solubility, high drug dosage, and short drug half-life in vivo. However, most of the existing nanomedicines possess the drawback of low drug-loading (generally less than 10%) associated with more carrier materials. For intravenous administration, the extensive use of carrier materials might cause systemic toxicity and impose an extra burden of degradation, metabolism, and excretion of the materials for patients. Therefore, on the premise of guaranteeing therapeutic effect and function, reducing or avoiding the use of carrier materials is a promising alternative approach to solve these problems. Recently, high drug-loading nanomedicines, which have a drug-loading content higher than 10%, are attracting increasing interest. According to the fabrication strategies of nanomedicines, high drug-loading nanomedicines are divided into four main classes: nanomedicines with inert porous material as carrier, nanomedicines with drug as part of carrier, carrier-free nanomedicines, and nanomedicines following niche and complex strategies. To date, most of the existing high drug-loading nanomedicines belong to the first class, and few research studies have focused on other classes. In this review, we investigate the research status of high drug-loading nanomedicines and discuss the features of their fabrication strategies and optimum proposal in detail. We also point out deficiencies and developing direction of high drug-loading nanomedicines. We envision that high drug-loading nanomedicines will occupy an important position in the field of drug-delivery systems, and hope that novel perspectives will be proposed for the development of high drug-loading nanomedicines.

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“…In our previous study, a multifunctional nanoparticle with an adjustable drug ratio and excellent delivery was developed. In the case, the loading of the two drugs in the nanoparticle, which are DOX and apogossypolone, met an optimal ratio by adjusting the amount of subsystems [39]. Based on the study, an excellent anti-HCC nanocarrier was designed.…”

Section: Introductionmentioning

confidence: 99%

Doxorubicin and ABT-199 Coencapsulated Nanocarriers for Targeted Delivery and Synergistic Treatment against Hepatocellular Carcinoma

Zhou

Fan

et al. 2019

Journal of Nanomaterials

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For the patients with hepatocellular carcinoma (HCC), conventional chemotherapy is insufficient or has no benefit. Although combination chemotherapy has been proven as an efficient strategy to enhance anti-HCC efficacy, some barriers, such as low bioavailability and side effects, are limiting clinical development. In order to overcome disadvantages of combination chemotherapy in HCC, targeted nanoparticles (NPs) simultaneously loaded with doxorubicin (DOX) and ABT-199 in an optimal synergistic ratio were developed. First, the most synergistic combination with DOX was screened from ABT-199, ABT-263, and ABT-737. Among them, ABT-199 showed optimal synergy with DOX in a ratio of 10 : 1. Then, cationic amphipathic starch (CSaSt) and hyaluronic acid (HA) were used in coencapsulations of those two drugs. Dual-drug synergistic nanoparticles (DDS NPs) were constructed by absorption of DOX NPs around ABT-199 micelles with an optimal ratio via electrostatic interaction. The shape of DDS NPs was similar to a raspberry, and the size was 112 6 ± 13 4 nm. The encapsulation efficiencies of DOX and ABT-199 in DDS NPs were 90 2 ± 4 3% and 94 7 ± 2 8%, respectively; meanwhile, the drug loadings were 1 5 ± 0 4% and 14 1 ± 1 1%, respectively. After 72 h of dialysis, 95% of ABT-199 remained and less than 50% of DOX was released. In vitro investigation showed that the drugs in DDS NPs maintained the treated effect in three HCC cell lines; moreover, DDS NPs could perform intracellular delivery of dual drugs and exhibited continuous release of the drugs into different targets. Low in vivo toxicity was found after the acute toxicity test. In vivo fluorescent imaging revealed that DDS NPs could efficiently target and accumulate in the tumor tissues and be maintained more than 72 h after intravenous injection. Compared with free drugs, DDS NPs with the same dosages exhibited a more significant antitumor effect in the HCC xenograft mouse model. The results indicated that DDS NPs have great potential in HCC chemotherapy.Tables S1 and S2: CI and dose reduction values for inhibition of BEL-7402, SMMC-7721, and Huh-7 by combining DOX with ABT-263 or ABT-737. The synergistic effects of these two combinations were less than combined DOX with . Especially in ABT-263 combined with DOX, it showed few synergy in three HCC cell lines. Figure S1: WST assay results of BEL-7402, SMMC-7721, and Huh-7 cells treated with dual drugs and DDS NPs. As the result show, the toxicity of empty NPs was almost none, and DDS NPs and free dual drugs have equal antiproliferating effect against three HCC cell lines in vitro. The result indicated that the DDS NPs could perform the synergistic anti-HCC effect of ABT-199 combined with DOX. (Supplementary Materials)

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Mulberry-like dual-drug complicated nanocarriers assembled with apogossypolone amphiphilic starch micelles and doxorubicin hyaluronic acid nanoparticles for tumor combination and targeted therapy

Cited by 84 publications

References 48 publications

Co-delivery nanocarriers targeting folate receptor and encapsulating 2-deoxyglucose and α-tocopheryl succinate enhance anti-tumor effect in vivo

Co-delivery nanocarriers targeting folate receptor and encapsulating 2-deoxyglucose and α-tocopheryl succinate enhance anti-tumor effect in vivo

High drug-loading nanomedicines: progress, current status, and prospects

Doxorubicin and ABT-199 Coencapsulated Nanocarriers for Targeted Delivery and Synergistic Treatment against Hepatocellular Carcinoma

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Mulberry-like dual-drug complicated nanocarriers assembled with apogossypolone amphiphilic starch micelles and doxorubicin hyaluronic acid nanoparticles for tumor combination and targeted therapy

Cited by 84 publications

References 48 publications

Co-delivery nanocarriers targeting folate receptor and encapsulating 2-deoxyglucose and &alpha;-tocopheryl succinate enhance anti-tumor effect in vivo

Co-delivery nanocarriers targeting folate receptor and encapsulating 2-deoxyglucose and &alpha;-tocopheryl succinate enhance anti-tumor effect in vivo

High drug-loading nanomedicines: progress, current status, and prospects

Doxorubicin and ABT-199 Coencapsulated Nanocarriers for Targeted Delivery and Synergistic Treatment against Hepatocellular Carcinoma

Contact Info

Product

Resources

About

Co-delivery nanocarriers targeting folate receptor and encapsulating 2-deoxyglucose and α-tocopheryl succinate enhance anti-tumor effect in vivo

Co-delivery nanocarriers targeting folate receptor and encapsulating 2-deoxyglucose and α-tocopheryl succinate enhance anti-tumor effect in vivo