Integration of an anti-tumor drug into nanocrystalline assemblies for sustained drug release

Yang, Xiangrui; Wu, Shichao; Li, Yang; Huang, Yu; Lin, Jun; Chen, Di; Ye, Shefang; Xie, Liping; Jiang, Yuan; Hou, Zhenqing

doi:10.1039/c4sc03392b

Cited by 20 publications

(26 citation statements)

References 46 publications

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“…HCPT and PPMTX were codissolved in acetone, forming a hybrid solution of drug and excipient. When the hybrid solution was injected into deionized water under sonication, a sudden change of solvent environment occurred, inducing the nucleation of HCPT nanocrystallines and the accompanying coprecipitation of PPMTX onto the growing HCPT nanocrystallines [ 38 , 39 ].…”

Section: Resultsmentioning

confidence: 99%

Dual-drug loaded nanoneedles with targeting property for efficient cancer therapy

Yang¹,

Wu²,

Xie³

et al. 2017

J Nanobiotechnol

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BackgroundSince the anticancer drugs have diverse inhibited mechanisms to the cancer cells, the use of two or more kinds of anticancer agents may achieve excellent therapeutic effects, especially to the drug-resistant tumors.ResultsIn this study, we developed a kind of dual drug [methotrexate (MTX) and 10-hydroxycamptothecine (HCPT)] loaded nanoneedles (DDNDs) with pronounced targeting property, high drug loading and prolonged drug release. The anti-solvent precipitation of the HCPT and MTX modified PEG-b-PLGA (PEG-b-PLGA-MTX, PPMTX) leads to nucleation of nanoneedles with nanocrystalline HCPT as the core wrapped with PPMTX as steric stabilizers. In vitro cell uptake studies showed that the DDNDs revealed an obviously targeting property and entered the HeLa cells easier than the nanoneedles without MTX modification. The cytotoxicity tests illustrated that the DDNDs possessed better killing ability to HeLa cells than the individual drugs or their mixture in the same dose, indicating its good synergistic effect and targeting property. The in vivo studies further confirmed these conclusions.ConclusionsThis approach led to a promising sustained drug delivery system for cancer diagnosis and treatment.Electronic supplementary materialThe online version of this article (10.1186/s12951-017-0326-x) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Dual-drug loaded nanoneedles with targeting property for efficient cancer therapy

Yang¹,

Wu²,

Xie³

et al. 2017

J Nanobiotechnol

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“…Its nanocrystalline form, protected by surfactants or polymers, was obtainable in an anti-solvent precipitation process with water as an anti-solvent in previous studies Yang et al, 2015;Zhao et al, 2015). For instance, our recent study showed that a membrane emulsifier-assisted anti-solvent precipitation could be employed for integration of HCPT nanoneedles with a polymer layer to achieve comet-shaped microparticles with the sustained release property (Yang et al, 2015). We emphasize that HCPT has distinct formula at different pH values, i.e.…”

Section: Resultsmentioning

confidence: 99%

“…In a standard experimental set-up, the fast mixing of an alkaline HCPT solution (pH ¼ 13) with an acidic MTX-chitosan one (pH ¼ 2.0) in the presence of ultrasound led to coprecipitation of both ingredients. According to our recent study (Yang et al, 2015), we hypothesize that the growth of HCPT nanocrystals was halted as they were encapsulated by the coprecipitation of the MTX-chitosan conjugate ( Figure 1A). The assumption is strongly supported by a zeta-potential value of +21.4 ± 2.1 mV, which demonstrates the interfacial presence of a positively-charged layer of MTX-chitosan conjugates on each nanoneedle.…”

Section: Resultsmentioning

confidence: 99%

A green approach to dual-drug nanoformulations with targeting and synergistic effects for cancer therapy

Yang

Lü

et al. 2017

Drug Delivery

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Exploration of efficient dual-drug nanohybrids, particularly those with high drug loading, specific targeting property, and long-termed stability, is of highly importance in cancer therapy. A pH-driven coprecipitation was performed in the aqueous phase to obtain a dual-drug nanoformulation, composed of 10-hydroxycamptothecine (HCPT) nanoneedles integrated with an exterior thin layer of the methotrexate (MTX)-chitosan conjugate. The high stability of nanohybrids in water and the targeting property provided by the MTX ingredient function synergistically to the prolonged and sustained drug release property in tumor tissues and the increased cellular uptake. The cytotoxicity test illustrates that dual-drug nanoneedles possess the remarkable killing ability to HeLa cells with the combination index at 0.33 ± 0.07. After cellular internalization, the release of both drug ingredients results in an excellent anticancer activity in vivo with the minimized adverse side effects. Design of a green approach to the carrier-free, dual-drug nanoformulations enables to develop emerging drug delivery systems for cancer diagnosis and treatment.

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“…Significant progress has been made, and many nanoparticle-based multifunctional drug delivery systems have been successfully prepared, which demonstrate a wide range of combined properties such as long circulating [3, 4], targeting [5–7], imaging [8–10], pH sensitivity [11, 12], and sustained drug release [9, 13]. …”

Section: Introductionmentioning

confidence: 99%

A New Method Without Organic Solvent to Targeted Nanodrug for Enhanced Anticancer Efficacy

Yang

Zou

et al. 2017

Nanoscale Res Lett

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Since the hydrophobic group is always essential to the synthesis of the drug-loaded nanoparticles, a majority of the methods rely heavily on organic solvent, which may not be completely removed and might be a potential threat to the patients. In this study, we completely “green” synthesized 10-hydroxycamptothecine (HCPT) loaded, folate (FA)-modified nanoneedles (HFNDs) for highly efficient cancer therapy with high drug loading, targeting property, and imaging capability. It should be noted that no organic solvent was used in the preparation process. In vitro cell uptake study and the in vivo distribution study showed that the HFNDs, with FA on the surface, revealed an obviously targeting property and entered the HeLa cells easier than the chitosan-HCPT nanoneedles without FA modified (NDs). The cytotoxicity tests illustrated that the HFNDs possessed better killing ability to HeLa cells than the individual drug or the NDs in the same dose, indicating its good anticancer effect. The in vivo anticancer experiment further revealed the pronounced anticancer effects and the lower side effects of the HFNDs. This new method without organic solvent will lead to a promising sustained drug delivery system for cancer diagnosis and treatment.

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Integration of an anti-tumor drug into nanocrystalline assemblies for sustained drug release

Abstract: A bio-inspired approach was used to integrate an anti-tumor drug into nanocrystalline assemblies for sustained drug release.

Cited by 20 publications

References 46 publications

Dual-drug loaded nanoneedles with targeting property for efficient cancer therapy

Dual-drug loaded nanoneedles with targeting property for efficient cancer therapy

A green approach to dual-drug nanoformulations with targeting and synergistic effects for cancer therapy

A New Method Without Organic Solvent to Targeted Nanodrug for Enhanced Anticancer Efficacy

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