Posted by The development of effective drug delivery systems is a key focus in pharmaceutical research, aiming to enhance therapeutic efficacy while minimizing adverse effects. Self-assembled nanostructures present a promising solution due to their tunable properties, biocompatibility, and ability to encapsulate and deliver therapeutic agents to specific targets. This review with 196 references examines recent advancements in drug-based self-assembled nanostructures for targeted delivery applications, including drug-drug conjugates, polymeric-based architectures, biomolecules, peptides, DNA, squalene conjugates and amphiphilic drugs –interestingly cyclodextrins are not mentioned. Various strategies for fabricating these nanostructures are discussed, with an emphasis on the design principles and mechanisms underlying their self-assembly and potential for targeted drug delivery to specific tissues or cells. Furthermore, the integration of targeting ligands, stimuli-responsive moieties and imaging agents into these nanostructures is explored for enhanced therapeutic outcomes and real-time monitoring.
In biological systems, numerous natural molecules demonstrate the ability to spontaneously form self-assembled nanostructures. For example, the self-assembly of lipids into liposomes facilitates efficient drug encapsulation and targeted delivery. This phenomenon is also observed in various biological processes, such as lipid particles forming oil droplets in water, polypeptides assembling into functional hemoglobin, the complex structures of ribosomal RNA and proteins, viral capsid formation and the organization of lipid bilayers within cellular membranes.
An important consideration in the design and application of nanostructures is the formation of the protein corona. This dynamic biomolecular layer adsorbs onto the surface of nanostructures upon their introduction to a biological environment. In doing so, this interaction can have a profound impact on the pharmacokinetics, biodistribution, cellular uptake and immunogenicity of the nanostructure. Accordingly, the formation of a protein corona can alter the targeting efficiency of nanostructures by masking ligands or modifying surface characteristics, which can impact their ability to bind specifically to target receptors. Moreover, this layer can result in off-target effects by directing nanostructures to unintended tissues or via triggering immune responses in the patient.
Reference:
Nsairat H, Lafi Z, Al-Najjar BO, Al-Samydai A, Saqallah FG, El-Tanani M, Oriquat GA, Sa’bi BM, Ibrahim AA, Dellinger AL, Alshaer W. How Advanced are Self-Assembled Nanomaterials for Targeted Drug Delivery? A Comprehensive Review of the Literature. Int J Nanomedicine. 2025;20:2133-2161
https://doi.org/10.2147/IJN.S490444