Synthesis and Assembly of Click‐Nucleic‐Acid‐Containing PEG–PLGA Nanoparticles for DNA Delivery

Abstract

Co-delivery of both chemotherapy drugs and siRNA from a single delivery vehicle can have a significant impact on cancer therapy due to the potential for overcoming issues such as drug resistance. However, the inherent chemical differences between charged nucleic acids and hydrophobic drugs have hindered entrapment of both components within a single carrier. While poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) (PEG-PLGA) copolymers have been used successfully for targeted delivery of chemotherapy drugs, loading of DNA or RNA has been poor. It is demonstrated that significant amounts of DNA can be encapsulated within PLGA-containing nanoparticles through the use of a new synthetic DNA analog, click nucleic acids (CNAs). First, triblock copolymers of PEG-CNA-PLGA are synthesized and then formulated into polymer nanoparticles from oil-in-water emulsions. The CNA-containing particles show high encapsulation of DNA complementary to the CNA sequence, whereas PEG-PLGA alone shows minimal DNA loading, and non-complementary DNA strands do not get encapsulated within the PEG-CNA-PLGA nanoparticles. Furthermore, the dye pyrene can be successfully co-loaded with DNA and lastly, a complex, larger DNA sequence that contains an overhang complementary to the CNA can also be encapsulated, demonstrating the potential utility of the CNA-containing particles as carriers for chemotherapy agents and gene silencers.

PLGA protein nanocarriers with tailor-made fluorescence/MRI/PET imaging modalities

“…[1][2][3][4][5] Poly(lactic-co-glycolic acid) (PLGA) has demonstrated optimal properties for the encapsulation of a large variety of therapeutic agents and it is extensively employed in nanomedicine. 6,7 Moreover, PLGA-based nanocarriers have been used as drug delivery systems to administer proteins, 8,9 DNA 10 and anticancer drugs among others. 1,11,12 Nonetheless, despite their compositional similarities, any novel PLGA-based drug delivery system will require a thorough evaluation to address potential toxicity issues and study the pharmacokinetics and the pharmacodynamics of each specific carrier.…”

Cancer‐Targeting Nanoparticles for Combinatorial Nucleic Acid Delivery

“…In particular, PLGA‐PEG carriers show desirable small molecule delivery, but their chemical properties and synthesis techniques are not conducive to coencapsulation with nucleic acids. To improve nucleic acid loading in PLGA‐PEG polymer nanoparticles, carriers can be loaded with synthetic nucleic acid analogs click nucleic acids (CNAs), which bind to nucleic acids in a sequence‐specific manner . On the other hand, to improve loading of small molecule drug into carriers optimized for nucleic acid delivery, the drug may be intercalated into therapeutic DNA prior to loading the agents into a delivery vehicle.…”

“…To improve nucleic acid loading in PLGA-PEG polymer nanoparticles, carriers can be loaded with synthetic nucleic acid analogs click nucleic acids (CNAs), which bind to nucleic acids in a sequence-specific manner. [38] On the other hand, to improve loading of small molecule drug into carriers optimized for nucleic acid delivery, the drug may be intercalated into therapeutic DNA prior to loading the agents into a delivery vehicle. Other nanoparticles, including inorganic nanoparticles, bind nucleic acids by covalent conjugation.…”

Targeted Nanomedicine to Treat Bone Metastasis

“…Similarly, reactivation of tumor-suppressor genes in cancer cells promotes their response to other therapies. A key challenge to the application of nucleic acids as therapy is their rapid degradation by nucleases or their stimulation of the immune system [126,127]. Due to their inherent negative charge and large molecular weights, nucleic acids also show little uptake into target cells, which is critical for their function.…”