Intelligent design of multifunctional lipid-coated nanoparticle platforms for cancer therapy - PubMed (original) (raw)

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Intelligent design of multifunctional lipid-coated nanoparticle platforms for cancer therapy

Srinivas Ramishetti et al. Ther Deliv. 2012 Dec.

Abstract

Nanotechnology is rapidly evolving and dramatically changing the paradigms of drug delivery. The small sizes, unique chemical properties, large surface areas, structural diversity and multifunctionality of nanoparticles prove to be greatly advantageous for combating notoriously therapeutically evasive diseases such as cancer. Multifunctional nanoparticles have been designed to enhance tumor uptake through either passive or active targeting, while also avoiding reticuloendothelial system uptake through the incorporation of PEG onto the surface. First-generation nanoparticle systems, such as liposomes, are good carriers for drugs and nucleic acid therapeutics, although they have some limitations. These lipid bilayers are now being utilized as excellent carriers for drug-loaded, solid core particles such as iron oxide, mesoporus silica and calcium phosphate. In this article, their design, as well as their multifunctional role in cancer therapy are discussed.

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Figures

Figure 1

Figure 1

Multifunctional nanoparticle.

Figure 2

Figure 2. Passive and active targeting

(A) Nanoparticles enter the tumor environment via the enhanced permeability and retention effect; (B) target-specific uptake by tumor cells is facilitated by receptor-specific ligands on the surface of nanoparticles. Reproduced and modified with permission from [57] © American Chemical Society (2009).

Figure 3

Figure 3. Supported bilayer coating of silica nanoparticles

(A) A negatively charged drug is adsorbed into the pores of a cationic mesoporous silica nanoparticle. (i) Other anions that are adsorbed more strongly can displace the loaded drugs. (ii) Fusion with a negatively charged liposome reduces the displacement, (iii) and further lipid exchange/fusion with cationic liposomes reduces it more. (B) Representative transmission electron microscopy images of (i) bare anionic mesoporous silica cores and protocells with (ii) single or (iii) dual supported bilayers formed after successive DOTAP and DOPS fusion/exchange steps (lipid-fixed and negative-stained). NP: Nanoparticle. Modified and reprinted with permission from [138] © American Chemical Society (2009).

Figure 4

Figure 4. Lipid bilayer supported multifunctional silica nanoparticle (protocell)

Reproduced with permission from [181] © American Chemical Society (2012).

Figure 5

Figure 5. Lipid-coated calcium phosphate nanoparticles

(A) Nontargeted and targeted LCP; (B) transmission electron microscopy images of LCP coated with DOTAP and DSPE–PEG. LCP: Lipid calcium phosphate. Reproduced with permission from [149] © American Chemical Society (2012).

Figure 6

Figure 6. Therapeutic effect of siRNA in liposomal calcium phosphate nanoparticles

(A) Photographs of lungs excised from tumor-bearing mice; (B) quantification of luciferase activity in lung metastasis; (C) survival analysis of B16F10 lung metastases bearing mice on day 19 after four treatments; and (D) intratumoral expression of VEGF after treatment. LCP: Lipid calcium phosphate; NP: Nanoparticle. Reproduced with permission from [151] © Macmillan Publishers Ltd. Molecular Therapy (2012).

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