**3. Polyamidoamine (PAMAM) dendrimers**

502 Non-Viral Gene Therapy

macromolecules to the target cells, tissues or organs. Therefore the development of more efficient delivery systems is regarded as one of the most promising strategies to solve these pharmaceutical hurdles. Specifically, delivery vectors must be designed to effectively complex with nucleic acid molecules and aid in overcoming intracellular barriers such as endosomal escape and cytoplasmic vector dissociation. For that reason, improvements on effective delivery have progressed rapidly. Among the different approaches under study, dendrimers are attracting a great interest for their well defined structure and great versatility in their chemistry that offer a unique platform for the rational design of efficient

Fig. 1. The effect of miR-21 knockdown on U251 and LN229 GBM cell proliferation. (A) miR-21 was overexpressed in six glioma cells. (B) In situ examination of miR-21 expression in U251 cells. Arrows highlight miR-21 in situ expression in U251 cells. Bar¼20 mm. (C、D) MTT cell proliferation assay. miR-21 knockdown in U251 and LN229 GBM inhibits cell proliferation in vitro and in vivo. (E) Cell-cycle profiles after PI staining. miR-21 knockdown induced G1 arrest in both U251 and LN229 GBM cells. (F). As-miR-21 and scramble ODN-transfected U251 and

LN229 GBM cells were analyzed using FCM to determine cell-cycle status.

antisense delivery systems.

Recently, a great deal of attention has been given to polyamidoamine (PAMAM) dendrimers; these are one of the most appropriate candidates for suitable carrier systems. PAMAM dendrimers represent an exciting new class of macromolecular architecture called dense star polymers. Unlike classical polymers, dendrimers have a high degree of molecular uniformity, a narrow molecular weight distribution, specific size and shape character [15]. The terminal amine groups of PAMAM dendrimers can be modified with different functionalities and can be linked with various biomolecules. These unique structural features of PAMAM dendrimers make them ideal nanoplatforms to conjugate biologically important substances.
