SPIONs Conjugate Supported Anticancer Drug Doxorubicin’s Delivery: Current Status, Challenges, and Prospects

Abstract

Considerable efforts have been directed towards development of nano-structured carriers to overcome the limitations of anticancer drug, doxorubicin’s, delivery to various cancer sites. The drug’s severe toxicity to cardio and hepatic systems, low therapeutic outcomes, inappropriate dose–demands, metastatic and general resistance, together with non-selectivity of the drug have led to the development of superparamagnetic iron oxide nanoparticles (SPIONs)-based drug delivery modules. Nano-scale polymeric co-encapsulation of the drug, doxorubicin, with SPIONs, the SPIONs surface end-groups’ cappings with small molecular entities, as well as structural modifications of the SPIONs’ surface-located functional end-groups, to attach the doxorubicin, have been achieved through chemical bonding by conjugation and cross-linking of natural and synthetic polymers, attachments of SPIONs made directly to the non-polymeric entities, and attachments made through mediation of molecular-spacer as well as non-spacer mediated attachments of several types of chemical entities, together with the physico-chemical bondings of the moieties, e.g., peptides, proteins, antibodies, antigens, aptamers, glycoproteins, and enzymes, etc. to the SPIONs which are capable of targeting multiple kinds of cancerous sites, have provided stable and functional SPIONs–based nano-carriers suitable for the systemic, and in vitro deliveries, together with being suitable for other biomedical/biotechnical applications. Together with the SPIONs inherent properties, and ability to respond to magnetic resonance, fluorescence-directed, dual-module, and molecular-level tumor imaging; as well as multi-modular cancer cell targeting; magnetic-field-inducible drug-elution capacity, and the SPIONs’ magnetometry-led feasibility to reach cancer action sites have made sensing, imaging, and drug and other payloads deliveries to cancerous sites for cancer treatment a viable option. Innovations in the preparation of SPIONs-based delivery modules, as biocompatible carriers; development of delivery route modalities; approaches to enhancing their drug delivery-cum-bioavailability have explicitly established the SPIONs’ versatility for oncological theranostics and imaging. The current review outlines the development of various SPIONs-based nano-carriers for targeted doxorubicin delivery to different cancer sites through multiple methods, modalities, and materials, wherein high-potential nano-structured platforms have been conceptualized, developed, and tested for, both, in vivo and in vitro conditions. The current state of the knowledge in this arena have provided definite dose-control, site-specificity, stability, transport feasibility, and effective onsite drug de-loading, however, with certain limitations, and these shortcomings have opened the field for further advancements by identifying the bottlenecks, suggestive and plausible remediation, as well as more clear directions for future development.

Combined Anti-Bacterial Actions of Lincomycin and Freshly Prepared Silver Nanoparticles: Overcoming the Resistance to Antibiotics and Enhancement of the Bioactivity

“…To explain these results, two hypotheses have been suggested: (i) the Ag ions may inhibit the development of biofilms in bacteria by entering the bacterial cell and interfering with the proteins and enzymes necessary for microbial adhesion [ 47 ]; (ii) the AgNPs may weaken the development of biofilms by preventing the production of exogenous polysaccharides (exopolysaccharides). The NPs prevent the bacterial cell wall’s layers of polysaccharides from forming a biofilm by entering the water channels (aquaporin) that carry water and nutrients [ 48 ].…”

Fe3O4 SPIONs in cancer theranostics—structure versus interactions with proteins and methods of their investigation

“…Superparamagnetic iron oxide nanoparticles (SPIONs) represent the group of metallic nanoparticles with structures based on the crystals of α-Fe 2 O 3 (hematite), γ-Fe 2 O 3 (maghemite) or Fe 3 O 4 (magnetite) [9]. These nanoparticles are composed primarily of iron oxides.…”

“…The corona significantly affects the nanoparticles' interactions with their chemical environment [88]. It is one of the reasons why the development of active transportation using SPIONs functionalized with directing ligands has stopped at the phase of pre-clinical tests [9]. The protein corona may mask the molecules of the substance used for functionalization and thus block the interactions between the directing ligands and the surface of tumour cells.…”

“…Because of the size, nanoparticles' physicochemical properties differ from those of macroscale materials. The differences are mainly related to the high surface area to volume ratios of nanostructures, resulting in their unique optical, electric and magnetic properties [9,10]. The possibility of biomedical use of nanomaterials is closely related to their size.…”

Synthesis of Iron Oxides and Influence on Final Sizes and Distribution in Bacterial Cellulose Applications

“…Such control is fundamental in certain applications, such as the production of superparamagnetic iron oxide nanoparticles (SPIONs), which are commonly used in the medical field [ 7 , 8 ]. In such applications, the control of the size distribution is essential, as very large particles can interfere with the action of SPIONs.…”