Original Article
Designing idiosyncratic hmPCL-siRNA nanoformulated capsules for silencing and cancer therapy

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Abstract

In this work, we have designed a siRNA-nanoformulation with mesoporous polycaprolactone (hmPCL) for silencing and cancer therapy. Average hollow core size of hmPCL nanocapsules used for nanoformulation is ~ 180 nm with shell thickness of 10-20 nm and mesopore size of ~ 5-10 nm in diameter. Idiosyncratic capsules are biocompatible which has been confirmed with normal lymphocyte, K562 leukaemia cancer cells and on HepG2/EGFP cancer cells. In 1 mg of hmPCL capsules up to 400 ng of siRNA can be loaded. This nanoformulation enables to tune the dose dependent delivery up to ~ 93.25% (373 ng) siRNA during therapy. hmPCL-siRNA nanoformulation mediated siRNA transfection on HepG2 cancer cells has been investigated and exhibited 32% silencing activity within 24 h of post transfection. Obtained results directed us that the hmPCL-siRNA nanoformulation could be an efficient tool in siRNA mediated therapy for knocking down the infected cells.

From the Clinical Editor

siRNA could be used in cancer therapy if naked nucleic acid could be transported using a suitable carrier. In this article, the authors developed a nano-carrier system using mesoporous polycaprolactone (hmPCL) and showed its efficacy in knocking down cancer cells. This approach may open another way of gene therapy.

Graphical abstract

Idiosyncratic mesoporous-PCL nanocapsules (hmPCL) have been synthesised through microemulsion technique and formulated with siRNA. Nanoformulated siRNA-hmPCL is a potential vector for siRNA mediated therapy and for knock down of infected cells.

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Section snippets

Materials

hmPCL nanocapsules have been synthesised using commercially available PCL (Mw ~ 60,000, Tm ~ 60 °C, Sigma-Aldrich) through an ultrasonicated microemulsion approach using SiO2 nanoparticles and micelles of Igepal CO-520 (Mn ~ 441, density ~ 0.997 g/mL at 25 °C, b.p. ~ 240 °C, Sigma-Aldrich) as hard and soft templates, respectively.

Design of hollow-core-shell mesoporous PCL capsules (hmPCL)

Core-shell SiO2@PCL nanoparticles and hmPCL nanocapsules have been synthesised as discussed in the experimental section (supporting file). A schematic representation is shown in supporting Figure S1 for the formation of hmPCL nanocapsules. Figure 1, A and B showed the FESEM micrographs of spherical core-shell SiO2@PCL nanoparticles of size around ~ 200 nm (dia.) where PCL chains are deposited on SiO2 nanoparticles (~ 120-150 nm) (Figure S2, A and B at low and high magnification, respectively). The

Discussions

To achieve the hmPCL, the polymer chains are deposited layer-by-layer in a controlled manner using the ultrasonication onto the sacrificial SiO2 nanoparticles in the presence of a surfactant (Igepal CO-520) [(C2H4O)5 · (C15H24O)]. Removal of the template SiO2 nanoparticles and the surfactant resulted the formation of PCL nanocapsules with central hollow core of size 110-120 nm and mesoporous (avg. ~ 5-10 nm) shell with monodispersed in size. The release is controlled by the electrostatic interaction

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  • Cited by (0)

    Any prior or upcoming presentation of abstracts at meetings regarding the research: None.

    The authors acknowledge the financial support from the Department of Science and Technology (DST) for Fast-Track Grant for Young Scientist (Ref: SR/FTP/ETA-0079/2011) and School of Life Science, University of Hyderabad for cell culture facilities.

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