Nanotechnology has opened up a world of possibilities for the treatment of brain disorders. Nanosystems can be designed to encapsulate, carry, and deliver a variety of therapeutic agents, including drugs and nucleic acids. Nanoparticles may also be formulated to contain photosensitizers or, on their own, serve as photothermal conversion agents for phototherapy. Furthermore, nano-delivery agents can enhance the efficacy of contrast agents for improved brain imaging and diagnostics. However, effective nano-delivery to the brain is seriously hampered by the formidable blood–brain barrier (BBB). Advances in understanding natural transport routes across the BBB have led to receptor-mediated transcytosis being exploited as a possible means of nanoparticle uptake. In this regard, the oligopeptide Angiopep-2, which has high BBB transcytosis capacity, has been utilized as a targeting ligand. Various organic and inorganic nanostructures have been functionalized with Angiopep-2 to direct therapeutic and diagnostic agents to the brain. Not only have these shown great promise in the treatment and diagnosis of brain cancer but they have also been investigated for the treatment of brain injury, stroke, epilepsy, Parkinson’s disease, and Alzheimer’s disease. This review focuses on studies conducted from 2010 to 2021 with Angiopep-2-modified nanoparticles aimed at the treatment and diagnosis of brain disorders.

Liver cancer is currently regarded as the second leading cause of cancer-related mortality globally and is the sixth most diagnosed malignancy. Selenium nanoparticles (SeNPs) have attracted favorable attention as nanocarriers for gene therapy, as they possess beneficial antioxidant and anticancer properties. This study aimed to design, functionalize and characterize SeNPs to efficiently bind, protect and deliver pCMV–Luc DNA to hepatocellular carcinoma (HepG2) cells. The SeNPs were synthesized by ascorbic acid reduction and functionalized with poly-L-lysine (PLL) to stabilize and confer positive charges to the nanoparticles. The SeNPs were further decorated with lactobionic acid (LA) to target the asialoglycoprotein receptors abundantly expressed on the surface of the hepatocytes. All SeNPs were spherical, in the nanoscale range (<130 nm) and were capable of successfully binding, compacting and protecting the pDNA against nuclease degradation. The functionalized SeNP nanocomplexes exhibited minimal cytotoxicity (<30%) with enhanced transfection efficiency in the cell lines tested. Furthermore, the targeted SeNP (LA–PLL–SeNP) nanocomplex showed significant (* p < 0.05, ** p < 0.01, **** p < 0.0001) transgene expression in the HepG2 cells compared to the receptor-negative embryonic kidney (HEK293) cells, confirming receptor-mediated endocytosis. Overall, these functionalized SeNPs exhibit favorable features of suitable gene nanocarriers for the treatment of liver cancer.

Overexpression of the c-myc proto-oncogene features prominently in most human cancers. Early studies established that inhibiting the expression of oncogenic c-myc, produced potent anti-cancer effects. This gave rise to the notion that an appropriate c-myc silencing agent might provide a broadly applicable and more effective form of cancer treatment than is currently available. The endogenous mechanism of RNA interference (RNAi), through which small RNA molecules induce gene silencing by binding to complementary mRNA transcripts, represents an attractive avenue for c-myc inhibition. However, the development of a clinically viable, anti-c-myc RNAi-based platform is largely dependent upon the design of an appropriate carrier of the effector nucleic acids. To date, organic and inorganic nanoparticles were assessed both in vitro and in vivo, as carriers of small interfering RNA (siRNA), DICER-substrate siRNA (DsiRNA), and short hairpin RNA (shRNA) expression plasmids, directed against the c-myc oncogene. We review here the various anti-c-myc RNAi-based nanosystems that have come to the fore, especially between 2005 and 2020.

Nanomedicine has introduced strategies that provide precise diagnosis and treatment with fewer side effects than traditional therapies. Treatments for neurodegenerative disorders, including Parkinson’s disease, are palliative, necessitating an innovative delivery system with a curative function. This study investigated a solid lipid nanoparticle (SLNP) system’s ability to bind and safely deliver siRNA in vitro. SLNPS were formulated using sphingomyelin and cholesterol, with Ginkgo biloba leaf extract (GBE) incorporated to enhance biocompatibility and neuroprotection. Poly-L-lysine (PLL) functionalization ensured successful siRNA binding, safe transport, and protection from nuclease degradation. SLNPs were physicochemically characterized, with binding and protection of siRNA assessed using agarose gels. Cytotoxicity, apoptotic induction, and cellular uptake studies were undertaken in the human neuroblastoma (SH-SY5Y) and embryonic kidney (HEK293) cells. The GBE-PLL-SLNPs had an average size of 93.2 nm and demonstrated enhanced binding and protection of the siRNA from enzyme digestion, with minimal cytotoxicity in HEK293 (<10%) and SH-SY5Y cells (<15%). Caspase 3/7 activity was significantly reduced in both cells, while efficient cellular uptake was noted. The present study provided a solid basis as a proof of principle study for future applications of the potential therapeutic in vitro, promising to address the unmet medical needs of patients with neurological disorders.

Background: Nucleic acid-mediated therapy holds immense potential in treating recalcitrant human diseases such as cancer. This is underscored by advances in understanding the mechanisms of gene regulation. In particular, the endogenous protective mechanism of gene silencing known as RNA interference (RNAi) has been extensively exploited. Methods: We review the developments from 2011 to 2021 using nano-graphene oxide, carbon nanotubes, fullerenes, carbon nanohorns, carbon nanodots and nanodiamonds for the delivery of therapeutic small RNA molecules. Results: Appropriately designed effector molecules such as small interfering RNA (siRNA) can, in theory, silence the expression of any disease-causing gene. Alternatively, siRNA can be generated in vivo by introducing plasmid-based short hairpin RNA (shRNA) expression vectors. Other small RNAs, such as micro RNA (miRNA), also function in post-transcriptional gene regulation and are aberrantly expressed under disease conditions. The miRNA-based therapy involves either restoration of miRNA function through the introduction of miRNA mimics; or the inhibition of miRNA function by delivering anti-miRNA oligomers. However, the large size, hydrophilicity, negative charge and nuclease-sensitivity of nucleic acids necessitate an appropriate carrier for their introduction as medicine into cells. Conclusion: While numerous organic and inorganic materials have been investigated for this purpose, the perfect carrier agent remains elusive. Carbon-based nanomaterials have received widespread attention in biotechnology recently due to their tunable surface characteristics and mechanical, electrical, optical and chemical properties.