Polyphosphazene nanoparticles for cytoplasmic release of doxorubicin with improved cytotoxicity against Dox-resistant tumor cells

Cheng, Zheng; Xu, Jing; Yao, Xiaping; Xu, Jing; Qiu, Liyan

doi:10.1016/j.jcis.2010.12.004

Cited by 65 publications

(40 citation statements)

References 41 publications

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“…25,26 As shown in Fig. 1d, DOX-PEG NPs only show a moderate increase of diameter and possess excellent stability in physiological saline (PBS) for a period of at least 7 days, whereas the un-functionalized DOX NPs quickly grow into large 30 agglomerates, owing to elimination of the surface charge of DOX NPs by zwitterions in PBS. The PEG-PLGA is expected to attach to the hydrophobic surface of the DOX NPs through noncovalent interactions and aid them to achieve good 25 biocompatibility and favorable stability.…”

Section: Synthesis Characterization and Surface Functionalization Ofmentioning

confidence: 98%

Smart doxorubicin nanoparticles with high drug payload for enhanced chemotherapy against drug resistance and cancer diagnosis

Zhou

Zhang

et al. 2015

Nanoscale

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Considering the obvious advantages in efficacy and price, doxorubicin (DOX) has been widely used for a range of cancers, which is usually encapsulated in various nanocarriers for drug delivery. Although effective, in most nanocarrier-based delivery systems, the drug loading capacity of DOX is rather low; this can lead to undesired systemic toxicity and excretion concern. Herein, we report for the first time the usage of pure doxorubicin nanoparticles (DOX NPs) without addition of any carriers for enhanced chemotherapy against drug-resistance. The drug payload reaches as high as 90.47%, which largely surpassed those in previous reports. These PEG stabilized DOX NPs exhibit good biocompatibility and stability, long blood circulation time, fast release in an acidic environment and high accumulation in tumors. Compared with free DOX, DOX NPs display a dramatically enhanced anticancer therapeutic efficacy in the inhibition of cell and tumor growth. Moreover, they can also be readily incorporated with other anticancer drugs for synergistic chemotherapy to overcome the drug resistance of cancers. The fluorescence properties of DOX also endow these NPs with imaging capabilities, thus making it a multifunctional system for diagnosis and treatment. This work demonstrates great potential of DOX NPs for cancer diagnosis, therapy and overcoming drug tolerance.

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Section: Synthesis Characterization and Surface Functionalization Ofmentioning

confidence: 98%

Smart doxorubicin nanoparticles with high drug payload for enhanced chemotherapy against drug resistance and cancer diagnosis

Zhou

Zhang

et al. 2015

Nanoscale

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“…These include the use of cell penetrating peptides, stimuli responsive polymers (endoosmolytic mechanism to induce the endosomal disruption and release by exploiting differential redox or pH environment) or use of fusogenic liposomes (fusogenic mechanism: emptying the particle in cytoplasm during the fusion of liposomal particles with the endosomal membrane) [158]. Zheng et al have reported pH responsive nanoparticles derived from PEGylated polyphosphazene laterally functionalized with N , N -diisopropylethylenediamine (DPA) [159]. The DPA units imparted pH triggered release property to the resulting nanoparticles as demonstrated by loading and release of DND-26, a fluorescent dye that preferentially accumulates in acidic compartments in a cell.…”

Section: Intracellular Trafficking and Subcellular Targetingmentioning

confidence: 99%

Insight into nanoparticle cellular uptake and intracellular targeting

Yameen

Choi

Vilos

et al. 2014

Journal of Controlled Release

671

484

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Collaborative efforts from the fields of biology, materials science, and engineering are leading to exciting progress in the development of nanomedicines. Since the targets of many therapeutic agents are localized in subcellular compartments, modulation of nanoparticle-cell interactions for an efficient cellular uptake through the plasma membrane, and the development of nanomedicines for precise delivery to subcellular compartments remain formidable challenges. The cellular internalization routes have a determining effect on the post-internalization fate and intracellular localization of nanoparticles. This review highlights the cellular uptake routes most relevant to the field of non-targeted nanomedicine, and presents an account of ligand targeted nanoparticles for receptor mediated cellular internalization as a strategy for modulating the cellular uptake of nanoparticles. Ligand targeted nanoparticles have been the main impetus behind the progress of nanomedicines towards the clinic. This strategy has even resulted in a remarkable development towards effective oral delivery of nanomedicines that can overcome the intestinal epithelial cellular barrier. A detailed overview of the recent developments towards subcellular targeting that is emerging as a platform for the next generation organelle specific nanomedicines is also provided. Each section of the review includes prospect, potential, and concrete expectations from the field of targeted nanomedicines and strategies to meet those expectations.

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“…Other possible mechanisms of TPGS to overcome MDR may include inhibition of efflux pump ATPase and substrate binding, generation of ROS, and alteration of membrane fluidity [58–61]. Zheng et al synthesized pH-sensitive polymers by linking N,N-diisopropylethylenediamine (DPA) onto the backbone of PEGylated polyphosphazene [62]. DOX was entrapped in the polymer to form self-assembled micelles and the IC 50 value of this formulation was 60-fold lower than free DOX against resistant MCF-7/ADR cells.…”

Section: Anthracycline Nanoparticles To Overcome Mdrmentioning

confidence: 99%

Anthracycline nano-delivery systems to overcome multiple drug resistance: A comprehensive review

Mumper

2013

Nano Today

125

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Anthracyclines (doxorubicin, daunorubicin, and idarubicin) are very effective chemotherapeutic drugs to treat many cancers; however, the development of multiple drug resistance (MDR) is one of the major limitations for their clinical applications. Nano-delivery systems have emerged as the novel cancer therapeutics to overcome MDR. Up until now, many anthracycline nano-delivery systems have been developed and reported to effectively circumvent MDR both in-vitro and in-vivo, and some of these systems have even advanced to clinical trials, such as the HPMA-doxorubicin (HPMA-DOX) conjugate. Doxil, a DOX PEGylated liposome formulation, was developed and approved by FDA in 1995. Unfortunately, this formulation does not address the MDR problem. In this comprehensive review, more than ten types of developed anthracycline nano-delivery systems to overcome MDR and their proposed mechanisms are covered and discussed, including liposomes; polymeric micelles, conjugate and nanoparticles; peptide/protein conjugates; solid-lipid, magnetic, gold, silica, and cyclodextrin nanoparticles; and carbon nanotubes.

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Polyphosphazene nanoparticles for cytoplasmic release of doxorubicin with improved cytotoxicity against Dox-resistant tumor cells

Cited by 65 publications

References 41 publications

Smart doxorubicin nanoparticles with high drug payload for enhanced chemotherapy against drug resistance and cancer diagnosis

Smart doxorubicin nanoparticles with high drug payload for enhanced chemotherapy against drug resistance and cancer diagnosis

Insight into nanoparticle cellular uptake and intracellular targeting

Anthracycline nano-delivery systems to overcome multiple drug resistance: A comprehensive review

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