Trends in polymeric delivery of nucleic acids to tumors

Yousefi, Afrouz; Storm, Gert; Schiffelers, Raymond M.; Mastrobattista, Enrico

doi:10.1016/j.jconrel.2013.05.040

Cited by 28 publications

(25 citation statements)

References 139 publications

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“…KillerRed-mediated ROS production has been reported to cause a variety of oxidative damages to lipids and cellular organs 16 , leading to an enhancement of p53-mediated apoptosis response in p53 gene-transfected cells 9 11 14 . To determine whether cell death in the photoactivated cells could be explained via the induction of apoptosis, we used the TUNEL assay to characterize apoptosis.…”

Section: Resultsmentioning

confidence: 99%

“…These avenues in the treatment of cancer can be approached with the development of effective gene delivery. Polymeric-based carriers offer great promise, however, they generally fail in attempts to translate in vitro effect to in vivo models 14 . Chemotherapy is one major approach for treating NSCLC; however, progression-free survival rates depend significantly on the individuals’ chemotherapy response and extent of tumour metastasis.…”

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confidence: 99%

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Highly specific in vivo gene delivery for p53-mediated apoptosis and genetic photodynamic therapies of tumour

et al. 2015

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Anticancer therapies are often compromised by nonspecific effects and challenged by tumour environments’ inherent physicochemical and biological characteristics. Often, therapeutic effect can be increased by addressing multiple parameters simultaneously. Here we report on exploiting extravasation due to inherent vascular leakiness for the delivery of a pH-sensitive polymer carrier. Tumours’ acidic microenvironment instigates a charge reversal that promotes cellular internalization where endosomes destabilize and gene delivery is achieved. We assess our carrier with an aggressive non-small cell lung carcinoma (NSCLC) in vivo model and achieve >30% transfection efficiency via systemic delivery. Rejuvenation of the p53 apoptotic pathway as well as expression of KillerRed protein for sensitization in photodynamic therapy (PDT) is accomplished. A single administration greatly suppresses tumour growth and extends median animal survival from 28 days in control subjects to 68 days. The carrier has capacity for multiple payloads for greater therapeutic response where inter-individual variability can compromise efficacy.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Highly specific in vivo gene delivery for p53-mediated apoptosis and genetic photodynamic therapies of tumour

et al. 2015

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“…Therefore, the development of safe and efficient gene delivery systems is an exciting challenge in the field of pharmaceutical research, in the attempt to provide potential platforms to be used for genetic therapy 11 12 . An interesting approach is based on the use of polymeric nanoparticles, which have been demonstrated to be suitable for a wide range of applications for the delivery of a number of substances; these nanoparticles have the aim of improving the biopharmaceutical features of the encapsulated drug as well as its sustained release 13 14 . Our research team recently developed a nanoparticle device made up of chitosan, poloxamer 188 and PLGA, that was able to efficiently encapsulate and deliver genetic material because it showed physicochemical parameters suitable for making it a possible candidate for systemic administration, low in vitro cytotoxicity and significant transfection features 15 .…”

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confidence: 99%

Delivery of miR-34a by chitosan/PLGA nanoplexes for the anticancer treatment of multiple myeloma

Cosco

Cilurzo

Maiuolo

et al. 2015

Sci Rep

121

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The encapsulation of miR-34a into chitosan/PLGA nanoparticles in order to obtain nanoplexes useful for the modulation of the biopharmaceutical features of the active compound was studied. The nanoplexes were obtained through nanoprecipitation and were characterized by a mean diameter of ~160 nm, a good size distribution and a positive surface charge. The structure of the nanoparticles allowed a high level of entrapment efficiency of the miR-34a and provided protection of the genetic material from the effects of RNase. A high degree of transfection efficiency of the nanoplexes and a significant in vitro antitumor effect against multiple myeloma cells was demonstrated. The therapeutic properties of the nanoplexes were evaluated in vivo against human multiple myeloma xenografts in NOD-SCID mice. The systemic injection of miR-34a mimic-loaded nanoparticles significantly inhibited tumor growth and translated into improved survival of the laboratory mice. RT-PCR analysis carried out on retrieved tumors demonstrated the presence of a high concentration of miR-34a mimics. The integrity of the nanoplexes remained intact and no organ toxicity was observed in treated animals.

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“…A wide range of biological barriers exist to protect the human body from invasion by foreign materials. 31,32 Skin, muscle, cellular and mucosal barriers can be considered among others. The nanocarriers need to pass these barriers and reach the blood circulation in order to access the target site for an efficient therapeutic efficacy.…”

Section: Biological Barriersmentioning

confidence: 99%

Polymeric nanocarriers for expected nanomedicine: current challenges and future prospects

et al. 2014

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Polymeric nanocarriers have an increasingly growing potential for clinical applications. The current and future expectation from a polymeric nanocarrier is to exhibit both diagnostic and therapeutic functions. Living organisms are very complex systems and have many challenges for a carrier system such as biocompatibility, biodistribution, side-effects, biological barriers. Therefore, a designed polymeric nanocarrier should possess multifunctional properties to overcome these obstacles towards its target site. However, currently there are few polymeric systems that can be used for both therapy and imaging in clinic studies. In the literature, there are many studies for developing new generation polymeric nanocarriers to obtain future smart and multifunctional nanomedicine. In this review, we discuss the new generation and promising polymeric nanocarriers, which exhibit active targeting, triggered release of contents, and imaging capability for in vivo studies.

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Trends in polymeric delivery of nucleic acids to tumors

Cited by 28 publications

References 139 publications

Highly specific in vivo gene delivery for p53-mediated apoptosis and genetic photodynamic therapies of tumour

Highly specific in vivo gene delivery for p53-mediated apoptosis and genetic photodynamic therapies of tumour

Delivery of miR-34a by chitosan/PLGA nanoplexes for the anticancer treatment of multiple myeloma

Polymeric nanocarriers for expected nanomedicine: current challenges and future prospects

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