PLGA-Carbon Nanotube Conjugates for Intercellular Delivery of Caspase-3 into Osteosarcoma Cells

Abstract

Cancer has arisen to be of the most prominent health care issues across the world in recent years. Doctors have used physiological intervention as well as chemical and radioactive therapeutics to treat cancer thus far. As an alternative to current methods, gene delivery systems with high efficiency, specificity, and safety that can reduce side effects such as necrosis of tissue are under development. Although viral vectors are highly efficient, concerns have arisen from the fact that viral vectors are sourced from lethal diseases. With this in mind, rod shaped nano-materials such as carbon nanotubes (CNTs) have become an attractive option for drug delivery due to the enhanced permeability and retention effect in tumors as well as the ability to penetrate the cell membrane. Here, we successfully engineered poly (lactic-co-glycolic) (PLGA) functionalized CNTs to reduce toxicity concerns, provide attachment sites for pro-apoptotic protein caspase-3 (CP3), and tune the temporal release profile of CP3 within bone cancer cells. Our results showed that CP3 was able to attach to functionalized CNTs, forming CNT-PLGA-CP3 conjugates. We show this conjugate can efficiently transduce cells at dosages as low as 0.05 μg/ml and suppress cell proliferation up to a week with no further treatments. These results are essential to showing the capabilities of PLGA functionalized CNTs as a non-viral vector gene delivery technique to tune cell fate.

Natural Product Modulators to Overcome Multidrug Resistance In Cancer

“…Their results showed that CP3 was able to attach to functionalized CNTs, forming CNT-PLGA-CP3 conjugates. They also observed that this conjugate efficiently transduced cells at dosages as low as 0.05 mg/ml and suppressed cell proliferation up to a week with no further treatments (149).…”

Derivatized Carbon Nanotubes for Gene Therapy in Mammalian and Plant Cells

“…The degradation rate of the surface polymer allowed the tuning of the siRNA release from the vector. Cheng et al [66] designed a poly-(lactic-co-glycolic acid) (PLGA) functionalized MWCNTs that assisted in the slow release of caspase-3 into osteosarcoma cells upon the enzymatic degradation of PLGA. Non-covalent linking of siRNA with CNTs has an advantage over simple chemical modifications.…”

Advances in Anticancer Protein Delivery using Micro‐/Nanoparticles

“…By functionalizing single wall carbon nanotube (SWCN) with poly (lactic‐co‐glycolic) acid (PLGA) to achieve high solubility and low cytotoxicity, Cheng et al used PLGA‐SWCN as a carrier to deliver caspase‐3 into osteosarcoma cell MG‐63. PLGA was degraded enzymatically after cellular internalization and released the conjugated caspase‐3 . In addition to polymers, proteins can be adsorbed onto CNT surfaces through van der Waals interactions and hydrophobic interactions to improve dispersability and bio‐compatibility of CNTs .…”

“…PLGA was degraded enzymatically after cellular internalization and released the conjugated caspase-3. [ 50 ] In addition to polymers, proteins can be adsorbed onto CNT surfaces through van der Waals interactions and hydrophobic interactions to improve dispersability and bio-compatibility of CNTs. [ 51,52 ] By adsorbing toxin ricin A chain protein (RTA) and a HER2 antibody non-covalently on multi-walled carbon nanotubes (MWNTs), Weng et al selectively targeted HER2 receptors on specifi c breast cancer cells and delivered RTA to its natural intracellular locus to inhibit protein synthesis.…”

“…Cell penetrating peptide (CPP), which can be classifi ed into cationic, amphipathic and hydrophobic, interacts with various cell surface molecules to deliver the tethered protein via multiple pathways, including direct translocation through membrane bilayers and endocytosis. [ 110 ] Granadillo et al used a cell penetrating and immunostimulatory peptide derived from the Limulus polyphemus protein (LALF [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] ) to deliver human papillomavirus (HPV) 16 E7 antigen for cancer immunotherapy. [ 111 ] Immunofl uorescence microscopy with J774 murine macrophages cell line confi rmed the cell penetrating ability of LALF 32-51 -E7 by the detectable fl uorescence signal after incubation for 30 min while no signal was detected with soluble E7.…”