PAMAM-Functionalized Cellulose Nanocrystals with Needle-Like Morphology for Effective Cancer Treatment

Abstract

Gene therapy is used to correct or compensate for diseases caused by gene defects and abnormalities. Improving the transfection efficiency and reducing the toxicity of gene carriers are the keys to gene therapy. Similar to a typical cationic gene carrier—polyethylenimine (PEI, 25 kDa)—the polyamidoamine (PAMAM) dendrimer also has a large number of amino groups. These amino groups can be complexed with nucleic acids after protonation under physiological conditions. However, the concentrated positive charge can cause undesirable cytotoxicity. Cellulose nanocrystals (CNCs) have good biocompatibility and unique needle-like morphology, and have been proven to be efficiently taken up by cells. In this article, three-dimensional spherical PMAMA dendrimers are conjugated onto the surface of CNCs to obtain a kind of needle-like cationic carrier (CNC-PAMAM). PAMAM dendrimers act as anchors to bind the plasmid DNAs (pDNA) to the surface of the CNC. The prepared CNC-based carrier showed high transfection efficiency and low toxicity. The CNC-PAMAM can effectively deliver the suicide gene to the tumor site, enabling the suicide gene/prodrug system (cytosine deaminase/5-fluorocytosine (CD/5-FC)) to play an effective anti-tumor role in vivo. This research demonstrates that the functionalization of CNCs with PAMAM dendrimers is an effective method for developing novel gene delivery systems.

The Influence of Cell Cycle Regulation on Chemotherapy

“…In the current cancer treatment, the regulation of the cell cycle is mainly to control the expression of related genes and the activity of intracellular enzymes, proteins, or signal factors [5][6][7]. For example, chemotherapeutic drugs such as methotrexate (MTX) or 5-fluorouracil (5-FU) mainly destroy the synthesis of nucleotides and DNA replication in the process of cell proliferation [8,9]. Curcumin can regulate growth factors, enzymes, transcription factors, kinases, inflammatory cytokines, and proapoptotic (by upregulation) and antiapoptotic (by downregulation) proteins [10].…”

Effects of morphology and size of nanoscale drug carriers on cellular uptake and internalization process: a review

“…124 Moreover, polyamidoamine (PAMAM)-CNC nanocarriers conveniently penetrate the cell and are internalized due to their particular needle morphology. 125 2.9. Cubic-shaped nanocarriers Cubosomes ‡ show inimitable characteristics, including a specic cubic shape, which facilitates their incorporation with lipophilic, hydrophilic, and amphiphilic pharmaceutics.…”

“…124 Moreover, polyamidoamine (PAMAM)-CNC nanocarriers conveniently penetrate the cell and are internalized due to their particular needle morphology. 125 …”

Recent Advances in Functional Polymer Materials for Energy, Water, and Biomedical Applications: A Review

“…They are widely investigated as carriers for anti-tumor drugs [137]. PAMAM (polyamidoamine) dendrimers are being studied as efficient carriers (vectors) in gene therapy [138][139][140]. They are synthesized in different sizes and shapes, thus providing well-shaped carriers designed with nanometric sizes.…”