Cationic polymers and their therapeutic potential

Samal, Sangram Keshari; Dash, Mamoni; Vlierberghe, Sandra Van; Kaplan, David L.; Chiellini, Emo; Blitterswijk, Clemens A. van; Moroni, Lorenzo; Dubruel, Peter

doi:10.1039/c2cs35094g

Cited by 594 publications

(435 citation statements)

References 353 publications

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“…Since more than a decade, pharmacists, material scientists and biophysicists are intensively studying the design, preparation and cell biological behavior of nanosized particles carrying nucleic acids (2)(3)(4)(5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Lysosomal capturing of cytoplasmic injected nanoparticles by autophagy: An additional barrier to non viral gene delivery

Remaut

Oorschot²,

Braeckmans

et al. 2014

Journal of Controlled Release

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Autophagy or 'self-eating' is a process by which defective organelles and foreign material can be cleared from the cell's cytoplasm and delivered to the lysosomes in which degradation occurs. It remains an open question, however, whether nanoparticles that did not enter the cell through endocytosis can also be captured from the cytoplasm by autophagy. We demonstrate that nanoparticles that are introduced directly in the cytoplasm of the cells by microinjection, can trigger an autophagy response. Moreover, both polystyrene beads and plasmid DNA containing poly-ethylene-imine complexes colocalize with autophagosomes and lysosomes, as was confirmed by electron microscopy.This indicates that cytoplasmic capturing of nanoparticles can occur by an autophagy response. The capturing of nanoparticles from the cytoplasm most likely limits the time frame in which efficient nucleic acid delivery can be obtained. Hence, autophagy forms an additional barrier to non-viral gene delivery, a notion that was not often taken into account before. Furthermore, these findings urges us to reconsider the idea that a single endosomal escape event is sufficient to have the long-lasting presence of nanoparticles in the cytoplasm of the cells.

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Section: Introductionmentioning

confidence: 99%

Lysosomal capturing of cytoplasmic injected nanoparticles by autophagy: An additional barrier to non viral gene delivery

Remaut

Oorschot²,

Braeckmans

et al. 2014

Journal of Controlled Release

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“…Cationic polymers have also been proposed as nonviral gene delivery systems, due to their flexible properties, facile synthesis, robustness and proven gene delivery efficiency. For further details about the most recent scientific advances in cationic polymers and their derivatives not only for gene delivery purposes but also for various alternative therapeutic applications, the reader is directed to the review in [179]. The use of liposomes combined with scaffolds may contribute to overcoming the issues of toxicity, long-term expression and silencing efficiency.…”

Section: Therapeutic Gene Deliverymentioning

confidence: 99%

Liposomes in tissue engineering and regenerative medicine

Monteiro

Martins

Reis

et al. 2014

J. R. Soc. Interface.

297

197

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Liposomes are vesicular structures made of lipids that are formed in aqueous solutions. Structurally, they resemble the lipid membrane of living cells. Therefore, they have been widely investigated, since the 1960s, as models to study the cell membrane, and as carriers for protection and/or delivery of bioactive agents. They have been used in different areas of research including vaccines, imaging, applications in cosmetics and tissue engineering. Tissue engineering is defined as a strategy for promoting the regeneration of tissues for the human body. This strategy may involve the coordinated application of defined cell types with structured biomaterial scaffolds to produce living structures. To create a new tissue, based on this strategy, a controlled stimulation of cultured cells is needed, through a systematic combination of bioactive agents and mechanical signals. In this review, we highlight the potential role of liposomes as a platform for the sustained and local delivery of bioactive agents for tissue engineering and regenerative medicine approaches.

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“…The surface charge on NPs plays an important role in the way NPs interact with cell surfaces, and it has been reported that cationic particles generally enhance cellular uptake. 8,9 Moreover, NPs are able not only to function as a sonosensitizer per se, but also as energy transducers. 10 Therefore, we engineered poly-methyl methacrylate coreshell NPs so as to load the meso-tetrakis (4-sulfonatophenyl) porphyrin (TPPS) onto their cationic surface to form an innovative sonosensitizing system, ie, TPPS-NPs.…”

Section: Introductionmentioning

confidence: 99%

Polymeric nanoparticles enhance the sonodynamic activity of meso-tetrakis (4-sulfonatophenyl) porphyrin in an in vitro neuroblastoma model

Canaparo¹,

Varchi²,

Ballestri³

et al. 2013

IJN

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Purpose Sonodynamic therapy is a developing noninvasive modality for cancer treatment, based on the selective activation of a sonosensitizer agent by acoustic cavitation. The activated sonosensitizer agent might generate reactive oxygen species leading to cancer cell death. We investigated the potential poly-methyl methacrylate core-shell nanoparticles (NPs) loaded with meso-tetrakis (4-sulfonatophenyl) porphyrin (TPPS) have to function as an innovative sonosensitizing system, ie, TPPS-NPs. Methods Shockwaves (SWs) generated by a piezoelectric device were used to induce acoustic cavitation. The cytotoxic effect of the sonodynamic treatment with TPPS-NPs and SWs was investigated on the human neuroblastoma cell line, SH-SY5Y. Cells were exposed for 12 hours to TPPS-NPs (100 μg/mL) and then to SWs (0.43 mJ/mm 2 for 500 impulses, 4 impulses/second). Treatment with SWs, TPPS, and NPs alone or in combination was carried out as control. Results There was a statistically significant decrease in SH-SY5Y cell proliferation after the sonodynamic treatment with TPPS-NPs and SWs. Indeed, there was a significant increase in necrotic (16.91% ± 3.89%) and apoptotic (27.45% ± 3.03%) cells at 48 hours. Moreover, a 15-fold increase in reactive oxygen species production for cells exposed to TPPS-NPs and SWs was observed at 1 hour compared with untreated cells. A statistically significant enhanced mRNA (messenger ribonucleic acid) expression of NRF2 ( P <0.001) and a significant downregulation of TIGAR ( P <0.05) and MAP3K5 ( P <0.05) genes was observed in cells exposed to TPPS-NPs and SWs at 24 hours, along with a statistically significant release of cytochrome c ( P <0.01) at 48 hours. Lastly, the sonosensitizing system was also investigated in an in vitro three-dimensional model, and the sonodynamic treatment significantly decreased the neuroblastoma spheroid growth. Conclusion The sonosensitizing properties of TPPS were significantly enhanced once loaded onto NPs, thus enhancing the sonodynamic treatment’s efficacy in an in vitro neuroblastoma model.

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Cationic polymers and their therapeutic potential

Cited by 594 publications

References 353 publications

Lysosomal capturing of cytoplasmic injected nanoparticles by autophagy: An additional barrier to non viral gene delivery

Lysosomal capturing of cytoplasmic injected nanoparticles by autophagy: An additional barrier to non viral gene delivery

Liposomes in tissue engineering and regenerative medicine

Polymeric nanoparticles enhance the sonodynamic activity of meso-tetrakis (4-sulfonatophenyl) porphyrin in an in vitro neuroblastoma model

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